Diabetes comprises a group of metabolic diseases characterized by hyperglycemia stemming from various factors.Current diabetes management primarily focuses on blood glucose control,yet it is inherently progressive,nec...Diabetes comprises a group of metabolic diseases characterized by hyperglycemia stemming from various factors.Current diabetes management primarily focuses on blood glucose control,yet it is inherently progressive,necessitating increased reliance on exogenous blood glucose control methods over time.Therefore,there is an urgent need to explore novel intervention strategies addressing both diabetes and its complications.The human intestinal microbiota,often referred to as the"second genome",exhibits significant diversity and plays a pivotal role in insulin resistance,glucose and lipid metabolism,and inflammatory response.Notably,Li and Guo have elucidated the involvement of intestinal flora in the pathogenesis of type 2 diabetes mellitus(T2DM)and proposed a novel therapeutic approach targeting intestinal microbes.This advancement enhances our comprehension of the multifaceted and multi-target regulation of T2DM by intestinal microflora,thereby offering fresh avenues for understanding its pathogenesis and clinical management.This letter briefly summarizes the role of intestinal flora in T2DM based on findings from animal experiments and clinical studies.Additionally,it discusses the potential clinical applications and challenges associated with targeting intestinal flora as therapeutic interventions.展开更多
BACKGROUND Impaired hypoglycaemic counterregulation has emerged as a critical concern for diabetic patients who may be hesitant to medically lower their blood glucose levels due to the fear of potential hypoglycaemic ...BACKGROUND Impaired hypoglycaemic counterregulation has emerged as a critical concern for diabetic patients who may be hesitant to medically lower their blood glucose levels due to the fear of potential hypoglycaemic reactions.However,the pathogenesis of hypoglycaemic counterregulation is still unclear.Glucagon-like peptide-1(GLP-1)and its analogues have been used as adjunctive therapies for type 1 diabetes mellitus(T1DM).The role of GLP-1 in counterregulatory dysfunction during hypoglycaemia in patients with T1DM has not been reported.AIM To explore the impact of intestinal GLP-1 on impaired hypoglycaemic counterregulation in type 1 diabetic mice.METHODS T1DM was induced in C57BL/6J mice using streptozotocin,followed by intraperitoneal insulin injections to create T1DM models with either a single episode of hypoglycaemia or recurrent episodes of hypoglycaemia(DH5).Immunofluorescence,Western blot,and enzyme-linked immunosorbent assay were employed to evaluate the influence of intestinal GLP-1 on the sympathetic-adrenal reflex and glucagon(GCG)secretion.The GLP-1 receptor agonist GLP-1(7-36)or the antagonist exendin(9-39)were infused into the terminal ileum or injected intraperitoneally to further investigate the role of intestinal GLP-1 in hypoglycaemic counterregulation in the model mice.RESULTS The expression levels of intestinal GLP-1 and its receptor(GLP-1R)were significantly increased in DH5 mice.Consecutive instances of excess of intestinal GLP-1 weakens the sympathetic-adrenal reflex,leading to dysfunction of adrenal counterregulation during hypoglycaemia.DH5 mice showed increased pancreaticδ-cell mass,cAMP levels inδcells,and plasma somatostatin concentrations,while cAMP levels in pancreaticαcells and plasma GCG levels decreased.Furthermore,GLP-1R expression in islet cells and plasma active GLP-1 levels were significantly increased in the DH5 group.Further experiments involving terminal ileal infusion and intraperitoneal injection in the model mice demonstrated that intestinal GLP-1 during recurrent hypoglycaemia hindered the secretion of the counterregulatory hormone GCG via the endocrine pathway.CONCLUSION Excessive intestinal GLP-1 is strongly associated with impaired counterregulatory responses to hypoglycaemia,leading to reduced appetite and compromised secretion of adrenaline,noradrenaline,and GCG during hypoglycaemia.展开更多
AIM:To investigate the effects of the somatostatin analogue,octreotide,on maltose and sucrase activities and expression of glucose transporter type 2(GLUT2) in obese rat intestinal mucosa.METHODS:We divided 49 Sprague...AIM:To investigate the effects of the somatostatin analogue,octreotide,on maltose and sucrase activities and expression of glucose transporter type 2(GLUT2) in obese rat intestinal mucosa.METHODS:We divided 49 Sprague-Dawley rats into a group of 31 high fat diet-induced obese rats and a group of 18 normal controls.The obese rats were separated into an octreotide treated group of 16 rats and an obese group of 15.The intervention group was injected with octreotide at 40μg/kg body weight every 12 h for 8 d.Rat body weight was measured weekly to calculate Lee's index.After euthanization,maltase and sucrase activities in the small intestine were measuredby activity assays,and the fasting plasma glucose level was measured.The expression of GLUT2 in small intestinal mucosa was analyzed by immunohistochem-istry,reverse transcriptase polymerase chain reaction and Western blotting assays.RESULTS:Body weight,Lee's index,fasting plasma glucose level,maltase activity in small intestinal mucosa,mucosa and apical GLUT2,GLUT2 mRNA and protein expression levels were all significantly higher in the obese group than in the normal control group(605.61±141.00 vs 378.54±111.75,337.61 ±10.82 vs 318.73±20.10,8.60±1.38 vs 7.33± 0.70,156.01±58.81 vs 50.43±30.49,390 744.2 ±62 469.21 vs 170 546.50±50 646.14,26 740.18 ±3809.60 vs 354.98±57.19,0.26±0.11 vs 0.07 ±0.02,and 2.08±0.59 vs 1.27±0.38,respectively,all P<0.01).Sucrase activity did not differ between the two groups.Octreotide intervention significantly decreased the body weight and fasting plasma glucose level of obese rats(508.27±94.39 vs 605.61±141.00,7.58±1.51 vs 8.60±1.38,respectively,all P<0.05).The intestinal mucosa and apical GLUT2,expression of GLUT2 mRNA and protein were also significantly lower in the octreotide intervention group than in the obese group(269 975.2 ±53 730.94 vs 390 744.2±62 469.21,3758.06± 364.51 vs 26 740.18±3809.60,0.08±0.02 vs 0.26± 0.11,and 1.31±0.27 vs 2.08±0.59,respectively,all P<0.01).CONCLUSION:High fat dietinduced obesity is associated with elevated intestinal maltase activity,GLUT2 expression,and permanent apical GLUT2 in the small intestinal mucosa of rats.Octreotide can inhibit these effects.展开更多
Objective:To investigate the intestinal flora in elderly patients with type 2 diabetes mellitus with early nephropathy.Methods:43 elderly patients with type 2 diabetes mellitus with early nephropathy(diabetic nephropa...Objective:To investigate the intestinal flora in elderly patients with type 2 diabetes mellitus with early nephropathy.Methods:43 elderly patients with type 2 diabetes mellitus with early nephropathy(diabetic nephropathy group)and 51 elderly patients with type 2 diabetes mellitus(type 2 diabetes mellitus group)admitted to our hospital from January 2021 to October 2022 were retrospectively analyzed,with 39 healthy people who underwent a physical examination in our hospital during the same period as the control group.The fecal specimens of the three groups were collected,and the 16S rDNAs of bacteria in the fecal samples were extracted,amplified,and sequenced for intestinal flora operational taxonomic unit(OTU)classification and Alpha diversity analysis.Results:(1)Intestinal flora OTUs:there were 545 intestinal flora OTUs unique to the control group,424 intestinal flora OTUs unique to diabetic nephropathy,and 321 intestinal flora OTUs unique to the type 2 diabetes group.There were 403 intestinal flora OTUs common to the control group and diabetic nephropathy group,256 intestinal flora OTUs common to the control group and type 2 diabetes group,and 298 intestinal flora OTUs common to the type 2 diabetes group and diabetic nephropathy group.235 intestinal flora OTUs were common to all 3 groups of subjects.(2)Alpha diversity:The statistical analysis indicated that there was a statistically significant difference(P<0.05)in the Alpha diversity of intestinal flora,as assessed by the Ace index and Simpson’s index,among the three subject groups.However,no statistical significance(P>0.05)was observed when comparing the Chao 1 index and Shannon index.Further observation of the Ace index and Simpson index in the three groups revealed that both the diabetic nephropathy group and the type 2 diabetes mellitus group had lower values than the control group.Conclusion:The diversity of intestinal flora decreases in elderly patients with type 2 diabetes mellitus with early nephropathy.展开更多
BACKGROUND Genetic factors of chronic intestinal ulcers are increasingly garnering attention.We present a case of chronic intestinal ulcers and bleeding associated with mu-tations of the activin A receptor type II-lik...BACKGROUND Genetic factors of chronic intestinal ulcers are increasingly garnering attention.We present a case of chronic intestinal ulcers and bleeding associated with mu-tations of the activin A receptor type II-like 1(ACVRL1)and phospholipase A2 group IVA(PLA2G4A)genes and review the available relevant literature.CASE SUMMARY A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain,diarrhea,and dark stools.At the onset 6 years ago,the patient had received treatment at a local hospital for abdominal pain persisting for 7 d,under the diagnosis of diffuse peritonitis,acute gangrenous appendicitis with perforation,adhesive intestinal obstruction,and pelvic abscess.The surgical treat-ment included exploratory laparotomy,appendectomy,intestinal adhesiolysis,and pelvic abscess removal.The patient’s condition improved and he was dis-charged.However,the recurrent episodes of abdominal pain and passage of black stools started again one year after discharge.On the basis of these features and results of subsequent colonoscopy,the clinical diagnosis was established as in-flammatory bowel disease(IBD).Accordingly,aminosalicylic acid,immunotherapy,and related symptomatic treatment were administered,but the symptoms of the patient did not improve significantly.Further investigations revealed mutations in the ACVRL1 and PLA2G4A genes.ACVRL1 and PLA2G4A are involved in angiogenesis and coagulation,respectively.This suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A genes.Oral Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical symptoms.CONCLUSION Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in IBD.Orally administered Kangfuxin liquid may have therapeutic potential.展开更多
The incidence of type 2 diabetes(T2DM)is rapidly increasing worldwide.However,the pathogenesis of T2DM has not yet been well explained.Recent evidence suggests that the intestinal microbiota composition is associated ...The incidence of type 2 diabetes(T2DM)is rapidly increasing worldwide.However,the pathogenesis of T2DM has not yet been well explained.Recent evidence suggests that the intestinal microbiota composition is associated with obesity and T2DM.In this review,we provide an overview about the mechanisms underlying the role of intestinal microbiota in the pathogenesis of T2DM.There is clear evidence that the intestinal microbiota influences the host through its effect on body weight,bile acid metabolism,proinflammatory activity and insulin resistance,and modulation of gut hormones.Modulating gut microbiota with the use of probiotics,prebiotics,antibiotics,and fecal microbiota transplantation may have benefits for improvement in glucose metabolism and insulin resistance in the host.Further studies are required to increase our understanding of the complex interplay between intestinal microbiota and the host with T2DM.Further studies may be able to boost the development of new effective therapeutic approaches for T2DM.展开更多
Intestinal neuronal dysplasia type B(IND-B)is a controversial condition among gastrointestinal neuromuscular disorders.Constipation is its most common clinical manifestation in patients.Despite intense scientific rese...Intestinal neuronal dysplasia type B(IND-B)is a controversial condition among gastrointestinal neuromuscular disorders.Constipation is its most common clinical manifestation in patients.Despite intense scientific research,there are still knowledge gaps regarding the diagnostic criteria for IND-B in the histopathological analysis of rectal biopsies.The guidelines published in the past three decades have directed diagnostic criteria for quantifying the number of ganglion cells in the nervous plexus of the enteric nervous system.However,it is very complex to distinguish numerically what is pathological from what is normal,mainly because of the difficulty in determining a reliable control group composed of healthy children without intestinal symptoms.Thus,a series of immunohistochemical markers have been proposed to assist in the histopathological analysis of the enteric nervous system.Several of these markers facilitate the identification of other structures of the enteric nervous system,in addition to ganglion cells.These structures may be related to the etiopathogenesis of IND-B and represent new possibilities for the histopathological diagnosis of this disease,providing a view beyond the number of ganglion cells.This review critically discusses the aspects related to the disease definitions and diagnostic criteria of this organic cause of constipation.展开更多
Background:Multimorbidity of intestinal cancer(IC),type 2 diabetes(T2D)and obesity is a complex set of diseases,affected by environmental and genetic risk factors.High-fat diet(HFD)and oral bacterial infection play im...Background:Multimorbidity of intestinal cancer(IC),type 2 diabetes(T2D)and obesity is a complex set of diseases,affected by environmental and genetic risk factors.High-fat diet(HFD)and oral bacterial infection play important roles in the etiology of these diseases through inflammation and various biological mechanisms.Methods:To study the complexity of this multimorbidity,we used the collaborative cross(CC)mouse genetics reference population.We aimed to study the multimorbidity of IC,T2D,and obesity using CC lines,measuring their responses to HFD and oral bacterial infection.The study used 63 mice of both sexes generated from two CC lines(IL557 and IL711).For 12 weeks,experimental mice were maintained on specific dietary regimes combined with co-infection with oral bacteria Porphyromonas gingivalis and Fusobacterium nucleatum,while control groups were not infected.Body weight(BW)and results of a intraperitoneal glucose tolerance test(IPGTT)were recorded at the end of 12 weeks,after which length and size of the intestines were assessed for polyp counts.Results:Polyp counts ranged between 2 and 10 per CC line.The combination of HFD and infection significantly reduced(P<.01)the colon polyp size of IL557 females to 2.5 cm 2,compared to the other groups.Comparing BW gain,IL557 males on HFD gained 18 g,while the females gained 10 g under the same conditions and showed the highest area under curve(AUC)values of 40000-45000(min mg/dL)in the IPGTT.Conclusion:The results show that mice from different genetic backgrounds respond differently to a high fat diet and oral infection in terms of polyp development and glucose tolerance,and this effect is gender related.展开更多
Intestinal neuronal dysplasia type B(IND-B) is a controversial entity among the gastrointestinal neuromuscular disorders. It may occur alone or associated with other neuropathies, such as Hirschsprung's disease(HD...Intestinal neuronal dysplasia type B(IND-B) is a controversial entity among the gastrointestinal neuromuscular disorders. It may occur alone or associated with other neuropathies, such as Hirschsprung's disease(HD). Chronic constipation is the most common clinical manifestation of patients. IND-B primarily affects young children and mimics HD, but has its own histopathologic features characterized mainly by hyperplasia of the submucosal nerve plexus. Thus, IND-B should be included in the differential diagnoses of organic causes of constipation. In recent years, an increasing number of cases of IND-B in adults have also been described, some presenting severe constipation since childhood and others with the onset of symptoms at adulthood. Despite the intense scientific research in the last decades, there are still knowledge gaps regarding definition, pathogenesis, diagnostic criteria and therapeutic possibilities for IND-B. However, in medical practice, we continue to encounter patients with severe constipation or intestinal obstruction who undergo to diagnostic investigation for HD and their rectal biopsies present hyperganglionosis in the submucosal nerve plexus and other features, consistent with the diagnosis of IND-B. This review critically discusses aspects related to the disease definitions, pathophysiology and genetics, epidemiology distribution, clinical presentation, diagnostic criteria and therapeutic possibilities of this still little-known organic cause of intestinal chronic constipation.展开更多
BACKGROUND:Although invasive ductal adenocarcinoma of the pancreas(PDAC) manifests as a relatively uniform histomorphological feature of the pancreatobiliary type,it may be complicated by metaplastic changes and heter...BACKGROUND:Although invasive ductal adenocarcinoma of the pancreas(PDAC) manifests as a relatively uniform histomorphological feature of the pancreatobiliary type,it may be complicated by metaplastic changes and heterogeneous gastric and intestinal elements.This study aimed to investigate the complication rate and clinicopathological significance of such heterogeneous elements.METHODS:Fifty-nine patients who underwent resection of PDAC were examined in this study.Immunohistochemically,tumors showing high expression(>25%) of the intestinal-type(INT) marker CDX2 were classified as PDAC with INT.Those with high expression(>25%) of the gastric-type(GAS) marker MUC5AC were classified as PDAC with GAS,while those with high expression of both markers were classified as PDAC with INT/GAS.These patients were compared with those with PDAC of the negative group in which neither markers was highly expressed to examine their clinicopathological significance.RESULTS:In the 59 patients,31(52.5%) showed high CDX2 or MUC5AC expression.Twenty-eight patients(47.5%) belonged to a negative group,11(18.6%) to a PDAC with INT group,15(25.4%) to a PDAC with GAS group,and 5(8.5%) to a PDAC with INT/GAS group.No significant differences were observed for age,gender,size,localization,T classification,or prognosis among the four groups.Although the PDAC with GAS group had well differentiated types significantly more than the other groups,the rate of lymph node metastasis in this group was significantly higher(PDAC with GAS:73%;other groups:36%).CONCLUSION:Complications with heterogeneous elements are not uncommon in PDAC,and this should be considered during the diagnosis and treatment of PDAC along with histogenesis of the disease.展开更多
Type 2 diabetes mellitus(T2DM),which is distinguished by increased glucose levels in the bloodstream,is a metabolic disease with a rapidly increasing incidence worldwide.Nevertheless,the etiology and characteristics o...Type 2 diabetes mellitus(T2DM),which is distinguished by increased glucose levels in the bloodstream,is a metabolic disease with a rapidly increasing incidence worldwide.Nevertheless,the etiology and characteristics of the mechanism of T2DM remain unclear.Recently,abundant evidence has indicated that the intestinal microbiota is crucially involved in the initiation and progression of T2DM.The gut microbiome,the largest microecosystem,engages in material and energy metabolism in the human body.In this review,we concentrated on the correlation between the gut flora and T2DM.Meanwhile,we summarized the pathogenesis involving the intestinal flora in T2DM,as well as therapeutic approaches aimed at modulating the gut microbiota for the management of T2DM.Through the analysis presented here,we draw attention to further exploration of these research directions.展开更多
AIM To compare the combinative andindividual effect of acarbose and gymnemic acid(GA) on maltose absorption and hydrolysis insmall intestine to determine whether nutrientcontrol in diabetic care can be improved bycomb...AIM To compare the combinative andindividual effect of acarbose and gymnemic acid(GA) on maltose absorption and hydrolysis insmall intestine to determine whether nutrientcontrol in diabetic care can be improved bycombination of them.METHODS The absorption and hydrolysis ofmaltose were studied by cyclic perfusion ofintestinal loops in situ and motility of theintestine was recorded with the intestinal ring invitro using Wistar rats.RESULTS The total inhibitory rate of maltoseabsorption was improved by the combination ofGA (0.1 g/L 1.0 g/L) and acarbose(0.1 mmol/L 2.0 mmol/L) throughout theireffective duration (P<0.05, U test of Mann-Whitney), although the improvement only couldbe seen at a Iow dosage during the first hour.With the combination, inhibitory duration of acarbose on maltose absorption was prolonged to 3 h and the inhibitory effect onset of GA was fastened to 15min. GA suppressed the intestinal mobility with a good correlation (r-0.98) to the inhibitory effect of GA on maltose absorption and the inhibitory effect of 2mmol/L (high dose) acarbose on maltose hydrolysis was dual modulated by 1 g/L GA in vivo indicating that the combined effects involved the functional alteration of intestinal barriers.CONCLUSION There are augmented effects of acarbose and GA, which involve pre-cellular and paracellular barriers. Diabetic care can be improved by employing the combination.展开更多
Objective: To observe the relationship between the different stages of type 2 diabetes mellitus(T2DM)and the intestinal flora and verify its underlying mechanism.Methods: T2DM rats were generated by high-fat diet(HFD)...Objective: To observe the relationship between the different stages of type 2 diabetes mellitus(T2DM)and the intestinal flora and verify its underlying mechanism.Methods: T2DM rats were generated by high-fat diet(HFD) combined with intraperitoneal streptozotocin(STZ) injection. The rats were divided into four groups: the control group(fed with normal feed for1 month), the HFD group(fed with HFD for 1 month), the T2DM group(HFD combined with STZ and blood glucose ≥11.1 m M), and the unformed T2DM model(Un-mod) group(HFD combined with STZ and blood glucose <11.1 m M). Feces were collected, and bacterial communities in the fecal samples were analyzed by 16S r RNA gene sequencing. The content of short-chain fatty acids(SCFAs) in feces was measured by gas chromatography. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of G protein-coupled receptor 41(GPR41) and GPR43.Results: At different stages of T2DM, the intestinal flora and SCFAs content of rats were significantly decreased(all P <.05). Our results indicated that g__Prevotella had a significant negative correlation, and g__Ruminococcus_torques_group and g__lachnoclastic had a significant positive correlation with blood glucose. The content of SCFAs, in particular acetate and butyrate, in rat feces of different stages of T2DM were significantly reduced, as well as GPR41 and GPR43 expression. The results in the Un-mod group were similar to the T2DM group, and the expression of GPR41 and GPR43 proteins were significantly higher than those in the T2DM group(both P <.001).Conclusion: The intestinal flora-SCFAs-GPR41/GPR43 network may be important in the development of T2DM. Decreasing blood glucose levels by regulating the intestinal flora may become a new therapeutic strategy for T2DM, which has very important clinical and social values.展开更多
A 75-year-old male presented with difficult defecationand increasing urinary frequency over a few months. He had a significant history of previous partial gastrectomy for gastric carcinoma 20 years prior. Computed tom...A 75-year-old male presented with difficult defecationand increasing urinary frequency over a few months. He had a significant history of previous partial gastrectomy for gastric carcinoma 20 years prior. Computed tomography of the abdomen and pelvis showed extensive lymphadenopathy, a gastric mass and rectal as well as bladder wall thickening with bilateral ureterohydronephrosis. Normal looking serosal surfaces of the bladder and bowel were seen on laparoscopy and a defunctioning ileostomy was created. Gastroscopy revealed a malignant mass while cystoscopy and sigmoidscopy found extensive tumour growth lining the mucosal surfaces. Biopsies from all sites were compatible with intestinal type adenocarcinoma of gastric origin with few signet ring cells. Metabolic response to palliative chemotherapy was good and the patient's symptoms have improved on follow-up four months post ileostomy. We discuss the immunohistochemical profile of the tumour and review the literature.展开更多
Objective The pathological significance of nitric oxide (NO) in the intestinal type radiation sickness. Methods: The intestinal type radiation sickness of BALB/c mice were induced byCo γ-radiation, andthe nitric oxid...Objective The pathological significance of nitric oxide (NO) in the intestinal type radiation sickness. Methods: The intestinal type radiation sickness of BALB/c mice were induced byCo γ-radiation, andthe nitric oxide synthase (NOS), mucosa structure and survival rate of intestinal gland were examined by using NADPH-diaphorase histochemistry, H-E staining, Feulgen’s reaction and intestinal gland counting techniques. Results: Compared with irradiated mice without (L--NAME ) treatment, the dilatation of intestinalcavity and blood vessels of mice treated with L-NAME were lessened, the survival rates of intestinal glandwere remarkably increased (P < 0. 01), the mucosal structure was obviously improved, and the amount ofNOS--positive structures or products were also reduced. Conclusion: Activation of NOS or increase of NOsynthesis might aggravate the acute pathological injuries of intestines of the irradiated mice, whereas administration of L-NAME has protective effect on the intestinal mucosa to certain extent.展开更多
文摘Diabetes comprises a group of metabolic diseases characterized by hyperglycemia stemming from various factors.Current diabetes management primarily focuses on blood glucose control,yet it is inherently progressive,necessitating increased reliance on exogenous blood glucose control methods over time.Therefore,there is an urgent need to explore novel intervention strategies addressing both diabetes and its complications.The human intestinal microbiota,often referred to as the"second genome",exhibits significant diversity and plays a pivotal role in insulin resistance,glucose and lipid metabolism,and inflammatory response.Notably,Li and Guo have elucidated the involvement of intestinal flora in the pathogenesis of type 2 diabetes mellitus(T2DM)and proposed a novel therapeutic approach targeting intestinal microbes.This advancement enhances our comprehension of the multifaceted and multi-target regulation of T2DM by intestinal microflora,thereby offering fresh avenues for understanding its pathogenesis and clinical management.This letter briefly summarizes the role of intestinal flora in T2DM based on findings from animal experiments and clinical studies.Additionally,it discusses the potential clinical applications and challenges associated with targeting intestinal flora as therapeutic interventions.
基金Supported by National Natural Science Foundation of China,No.81471048.
文摘BACKGROUND Impaired hypoglycaemic counterregulation has emerged as a critical concern for diabetic patients who may be hesitant to medically lower their blood glucose levels due to the fear of potential hypoglycaemic reactions.However,the pathogenesis of hypoglycaemic counterregulation is still unclear.Glucagon-like peptide-1(GLP-1)and its analogues have been used as adjunctive therapies for type 1 diabetes mellitus(T1DM).The role of GLP-1 in counterregulatory dysfunction during hypoglycaemia in patients with T1DM has not been reported.AIM To explore the impact of intestinal GLP-1 on impaired hypoglycaemic counterregulation in type 1 diabetic mice.METHODS T1DM was induced in C57BL/6J mice using streptozotocin,followed by intraperitoneal insulin injections to create T1DM models with either a single episode of hypoglycaemia or recurrent episodes of hypoglycaemia(DH5).Immunofluorescence,Western blot,and enzyme-linked immunosorbent assay were employed to evaluate the influence of intestinal GLP-1 on the sympathetic-adrenal reflex and glucagon(GCG)secretion.The GLP-1 receptor agonist GLP-1(7-36)or the antagonist exendin(9-39)were infused into the terminal ileum or injected intraperitoneally to further investigate the role of intestinal GLP-1 in hypoglycaemic counterregulation in the model mice.RESULTS The expression levels of intestinal GLP-1 and its receptor(GLP-1R)were significantly increased in DH5 mice.Consecutive instances of excess of intestinal GLP-1 weakens the sympathetic-adrenal reflex,leading to dysfunction of adrenal counterregulation during hypoglycaemia.DH5 mice showed increased pancreaticδ-cell mass,cAMP levels inδcells,and plasma somatostatin concentrations,while cAMP levels in pancreaticαcells and plasma GCG levels decreased.Furthermore,GLP-1R expression in islet cells and plasma active GLP-1 levels were significantly increased in the DH5 group.Further experiments involving terminal ileal infusion and intraperitoneal injection in the model mice demonstrated that intestinal GLP-1 during recurrent hypoglycaemia hindered the secretion of the counterregulatory hormone GCG via the endocrine pathway.CONCLUSION Excessive intestinal GLP-1 is strongly associated with impaired counterregulatory responses to hypoglycaemia,leading to reduced appetite and compromised secretion of adrenaline,noradrenaline,and GCG during hypoglycaemia.
基金Supported by Grants from the National Natural Sciences Foundation of China,No.30870919Sichuan Provincial Department of Science and Technology,No.2010SZ0176
文摘AIM:To investigate the effects of the somatostatin analogue,octreotide,on maltose and sucrase activities and expression of glucose transporter type 2(GLUT2) in obese rat intestinal mucosa.METHODS:We divided 49 Sprague-Dawley rats into a group of 31 high fat diet-induced obese rats and a group of 18 normal controls.The obese rats were separated into an octreotide treated group of 16 rats and an obese group of 15.The intervention group was injected with octreotide at 40μg/kg body weight every 12 h for 8 d.Rat body weight was measured weekly to calculate Lee's index.After euthanization,maltase and sucrase activities in the small intestine were measuredby activity assays,and the fasting plasma glucose level was measured.The expression of GLUT2 in small intestinal mucosa was analyzed by immunohistochem-istry,reverse transcriptase polymerase chain reaction and Western blotting assays.RESULTS:Body weight,Lee's index,fasting plasma glucose level,maltase activity in small intestinal mucosa,mucosa and apical GLUT2,GLUT2 mRNA and protein expression levels were all significantly higher in the obese group than in the normal control group(605.61±141.00 vs 378.54±111.75,337.61 ±10.82 vs 318.73±20.10,8.60±1.38 vs 7.33± 0.70,156.01±58.81 vs 50.43±30.49,390 744.2 ±62 469.21 vs 170 546.50±50 646.14,26 740.18 ±3809.60 vs 354.98±57.19,0.26±0.11 vs 0.07 ±0.02,and 2.08±0.59 vs 1.27±0.38,respectively,all P<0.01).Sucrase activity did not differ between the two groups.Octreotide intervention significantly decreased the body weight and fasting plasma glucose level of obese rats(508.27±94.39 vs 605.61±141.00,7.58±1.51 vs 8.60±1.38,respectively,all P<0.05).The intestinal mucosa and apical GLUT2,expression of GLUT2 mRNA and protein were also significantly lower in the octreotide intervention group than in the obese group(269 975.2 ±53 730.94 vs 390 744.2±62 469.21,3758.06± 364.51 vs 26 740.18±3809.60,0.08±0.02 vs 0.26± 0.11,and 1.31±0.27 vs 2.08±0.59,respectively,all P<0.01).CONCLUSION:High fat dietinduced obesity is associated with elevated intestinal maltase activity,GLUT2 expression,and permanent apical GLUT2 in the small intestinal mucosa of rats.Octreotide can inhibit these effects.
文摘Objective:To investigate the intestinal flora in elderly patients with type 2 diabetes mellitus with early nephropathy.Methods:43 elderly patients with type 2 diabetes mellitus with early nephropathy(diabetic nephropathy group)and 51 elderly patients with type 2 diabetes mellitus(type 2 diabetes mellitus group)admitted to our hospital from January 2021 to October 2022 were retrospectively analyzed,with 39 healthy people who underwent a physical examination in our hospital during the same period as the control group.The fecal specimens of the three groups were collected,and the 16S rDNAs of bacteria in the fecal samples were extracted,amplified,and sequenced for intestinal flora operational taxonomic unit(OTU)classification and Alpha diversity analysis.Results:(1)Intestinal flora OTUs:there were 545 intestinal flora OTUs unique to the control group,424 intestinal flora OTUs unique to diabetic nephropathy,and 321 intestinal flora OTUs unique to the type 2 diabetes group.There were 403 intestinal flora OTUs common to the control group and diabetic nephropathy group,256 intestinal flora OTUs common to the control group and type 2 diabetes group,and 298 intestinal flora OTUs common to the type 2 diabetes group and diabetic nephropathy group.235 intestinal flora OTUs were common to all 3 groups of subjects.(2)Alpha diversity:The statistical analysis indicated that there was a statistically significant difference(P<0.05)in the Alpha diversity of intestinal flora,as assessed by the Ace index and Simpson’s index,among the three subject groups.However,no statistical significance(P>0.05)was observed when comparing the Chao 1 index and Shannon index.Further observation of the Ace index and Simpson index in the three groups revealed that both the diabetic nephropathy group and the type 2 diabetes mellitus group had lower values than the control group.Conclusion:The diversity of intestinal flora decreases in elderly patients with type 2 diabetes mellitus with early nephropathy.
基金Supported by the Science and Technology Research Foundation of Guizhou Province,No.QKHJC-ZK[2022]YB642Science and Technology Research Foundation of Hubei Province,No.2022BCE030+2 种基金Science and Technology Research Foundation of Zunyi City,No.ZSKH-HZ(2022)344Research Project on Traditional Chinese Medicine and Ethnic Medicine Science and Technology of Guizhou Provincial Administration of Traditional Chinese Medicine,No.QZYY-2023-021Science and Technology Research Foundation of Bijie City,No.BKH[2022]8.
文摘BACKGROUND Genetic factors of chronic intestinal ulcers are increasingly garnering attention.We present a case of chronic intestinal ulcers and bleeding associated with mu-tations of the activin A receptor type II-like 1(ACVRL1)and phospholipase A2 group IVA(PLA2G4A)genes and review the available relevant literature.CASE SUMMARY A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain,diarrhea,and dark stools.At the onset 6 years ago,the patient had received treatment at a local hospital for abdominal pain persisting for 7 d,under the diagnosis of diffuse peritonitis,acute gangrenous appendicitis with perforation,adhesive intestinal obstruction,and pelvic abscess.The surgical treat-ment included exploratory laparotomy,appendectomy,intestinal adhesiolysis,and pelvic abscess removal.The patient’s condition improved and he was dis-charged.However,the recurrent episodes of abdominal pain and passage of black stools started again one year after discharge.On the basis of these features and results of subsequent colonoscopy,the clinical diagnosis was established as in-flammatory bowel disease(IBD).Accordingly,aminosalicylic acid,immunotherapy,and related symptomatic treatment were administered,but the symptoms of the patient did not improve significantly.Further investigations revealed mutations in the ACVRL1 and PLA2G4A genes.ACVRL1 and PLA2G4A are involved in angiogenesis and coagulation,respectively.This suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A genes.Oral Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical symptoms.CONCLUSION Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in IBD.Orally administered Kangfuxin liquid may have therapeutic potential.
文摘The incidence of type 2 diabetes(T2DM)is rapidly increasing worldwide.However,the pathogenesis of T2DM has not yet been well explained.Recent evidence suggests that the intestinal microbiota composition is associated with obesity and T2DM.In this review,we provide an overview about the mechanisms underlying the role of intestinal microbiota in the pathogenesis of T2DM.There is clear evidence that the intestinal microbiota influences the host through its effect on body weight,bile acid metabolism,proinflammatory activity and insulin resistance,and modulation of gut hormones.Modulating gut microbiota with the use of probiotics,prebiotics,antibiotics,and fecal microbiota transplantation may have benefits for improvement in glucose metabolism and insulin resistance in the host.Further studies are required to increase our understanding of the complex interplay between intestinal microbiota and the host with T2DM.Further studies may be able to boost the development of new effective therapeutic approaches for T2DM.
基金São Paulo Research Foundation(FAPESP),No.2017/26205-9.
文摘Intestinal neuronal dysplasia type B(IND-B)is a controversial condition among gastrointestinal neuromuscular disorders.Constipation is its most common clinical manifestation in patients.Despite intense scientific research,there are still knowledge gaps regarding the diagnostic criteria for IND-B in the histopathological analysis of rectal biopsies.The guidelines published in the past three decades have directed diagnostic criteria for quantifying the number of ganglion cells in the nervous plexus of the enteric nervous system.However,it is very complex to distinguish numerically what is pathological from what is normal,mainly because of the difficulty in determining a reliable control group composed of healthy children without intestinal symptoms.Thus,a series of immunohistochemical markers have been proposed to assist in the histopathological analysis of the enteric nervous system.Several of these markers facilitate the identification of other structures of the enteric nervous system,in addition to ganglion cells.These structures may be related to the etiopathogenesis of IND-B and represent new possibilities for the histopathological diagnosis of this disease,providing a view beyond the number of ganglion cells.This review critically discusses the aspects related to the disease definitions and diagnostic criteria of this organic cause of constipation.
文摘Background:Multimorbidity of intestinal cancer(IC),type 2 diabetes(T2D)and obesity is a complex set of diseases,affected by environmental and genetic risk factors.High-fat diet(HFD)and oral bacterial infection play important roles in the etiology of these diseases through inflammation and various biological mechanisms.Methods:To study the complexity of this multimorbidity,we used the collaborative cross(CC)mouse genetics reference population.We aimed to study the multimorbidity of IC,T2D,and obesity using CC lines,measuring their responses to HFD and oral bacterial infection.The study used 63 mice of both sexes generated from two CC lines(IL557 and IL711).For 12 weeks,experimental mice were maintained on specific dietary regimes combined with co-infection with oral bacteria Porphyromonas gingivalis and Fusobacterium nucleatum,while control groups were not infected.Body weight(BW)and results of a intraperitoneal glucose tolerance test(IPGTT)were recorded at the end of 12 weeks,after which length and size of the intestines were assessed for polyp counts.Results:Polyp counts ranged between 2 and 10 per CC line.The combination of HFD and infection significantly reduced(P<.01)the colon polyp size of IL557 females to 2.5 cm 2,compared to the other groups.Comparing BW gain,IL557 males on HFD gained 18 g,while the females gained 10 g under the same conditions and showed the highest area under curve(AUC)values of 40000-45000(min mg/dL)in the IPGTT.Conclusion:The results show that mice from different genetic backgrounds respond differently to a high fat diet and oral infection in terms of polyp development and glucose tolerance,and this effect is gender related.
基金Supported by Sao Paulo Research Foundation(FAPESP)No.2014/042271-1
文摘Intestinal neuronal dysplasia type B(IND-B) is a controversial entity among the gastrointestinal neuromuscular disorders. It may occur alone or associated with other neuropathies, such as Hirschsprung's disease(HD). Chronic constipation is the most common clinical manifestation of patients. IND-B primarily affects young children and mimics HD, but has its own histopathologic features characterized mainly by hyperplasia of the submucosal nerve plexus. Thus, IND-B should be included in the differential diagnoses of organic causes of constipation. In recent years, an increasing number of cases of IND-B in adults have also been described, some presenting severe constipation since childhood and others with the onset of symptoms at adulthood. Despite the intense scientific research in the last decades, there are still knowledge gaps regarding definition, pathogenesis, diagnostic criteria and therapeutic possibilities for IND-B. However, in medical practice, we continue to encounter patients with severe constipation or intestinal obstruction who undergo to diagnostic investigation for HD and their rectal biopsies present hyperganglionosis in the submucosal nerve plexus and other features, consistent with the diagnosis of IND-B. This review critically discusses aspects related to the disease definitions, pathophysiology and genetics, epidemiology distribution, clinical presentation, diagnostic criteria and therapeutic possibilities of this still little-known organic cause of intestinal chronic constipation.
文摘BACKGROUND:Although invasive ductal adenocarcinoma of the pancreas(PDAC) manifests as a relatively uniform histomorphological feature of the pancreatobiliary type,it may be complicated by metaplastic changes and heterogeneous gastric and intestinal elements.This study aimed to investigate the complication rate and clinicopathological significance of such heterogeneous elements.METHODS:Fifty-nine patients who underwent resection of PDAC were examined in this study.Immunohistochemically,tumors showing high expression(>25%) of the intestinal-type(INT) marker CDX2 were classified as PDAC with INT.Those with high expression(>25%) of the gastric-type(GAS) marker MUC5AC were classified as PDAC with GAS,while those with high expression of both markers were classified as PDAC with INT/GAS.These patients were compared with those with PDAC of the negative group in which neither markers was highly expressed to examine their clinicopathological significance.RESULTS:In the 59 patients,31(52.5%) showed high CDX2 or MUC5AC expression.Twenty-eight patients(47.5%) belonged to a negative group,11(18.6%) to a PDAC with INT group,15(25.4%) to a PDAC with GAS group,and 5(8.5%) to a PDAC with INT/GAS group.No significant differences were observed for age,gender,size,localization,T classification,or prognosis among the four groups.Although the PDAC with GAS group had well differentiated types significantly more than the other groups,the rate of lymph node metastasis in this group was significantly higher(PDAC with GAS:73%;other groups:36%).CONCLUSION:Complications with heterogeneous elements are not uncommon in PDAC,and this should be considered during the diagnosis and treatment of PDAC along with histogenesis of the disease.
基金Jilin Provincial Science and Technology Department,No.20210204029YYJilin Provincial Natural Science Foundation Projects,No.YDZJ202201ZYTS151.
文摘Type 2 diabetes mellitus(T2DM),which is distinguished by increased glucose levels in the bloodstream,is a metabolic disease with a rapidly increasing incidence worldwide.Nevertheless,the etiology and characteristics of the mechanism of T2DM remain unclear.Recently,abundant evidence has indicated that the intestinal microbiota is crucially involved in the initiation and progression of T2DM.The gut microbiome,the largest microecosystem,engages in material and energy metabolism in the human body.In this review,we concentrated on the correlation between the gut flora and T2DM.Meanwhile,we summarized the pathogenesis involving the intestinal flora in T2DM,as well as therapeutic approaches aimed at modulating the gut microbiota for the management of T2DM.Through the analysis presented here,we draw attention to further exploration of these research directions.
基金Supported by Grant for Promotion of Science from Tottori Bioscience Foundation(1997-1998)Japan and Japanese Government(Ministry of Education,Science and Culture of Japan,MONBUSHO)scholarship No.933241(1994-1999)Japan in part.Dr.Luo was supported by the scholarships.
文摘AIM To compare the combinative andindividual effect of acarbose and gymnemic acid(GA) on maltose absorption and hydrolysis insmall intestine to determine whether nutrientcontrol in diabetic care can be improved bycombination of them.METHODS The absorption and hydrolysis ofmaltose were studied by cyclic perfusion ofintestinal loops in situ and motility of theintestine was recorded with the intestinal ring invitro using Wistar rats.RESULTS The total inhibitory rate of maltoseabsorption was improved by the combination ofGA (0.1 g/L 1.0 g/L) and acarbose(0.1 mmol/L 2.0 mmol/L) throughout theireffective duration (P<0.05, U test of Mann-Whitney), although the improvement only couldbe seen at a Iow dosage during the first hour.With the combination, inhibitory duration of acarbose on maltose absorption was prolonged to 3 h and the inhibitory effect onset of GA was fastened to 15min. GA suppressed the intestinal mobility with a good correlation (r-0.98) to the inhibitory effect of GA on maltose absorption and the inhibitory effect of 2mmol/L (high dose) acarbose on maltose hydrolysis was dual modulated by 1 g/L GA in vivo indicating that the combined effects involved the functional alteration of intestinal barriers.CONCLUSION There are augmented effects of acarbose and GA, which involve pre-cellular and paracellular barriers. Diabetic care can be improved by employing the combination.
基金supported by the National Natural Science Foundation of China (81973535 and 81773960)
文摘Objective: To observe the relationship between the different stages of type 2 diabetes mellitus(T2DM)and the intestinal flora and verify its underlying mechanism.Methods: T2DM rats were generated by high-fat diet(HFD) combined with intraperitoneal streptozotocin(STZ) injection. The rats were divided into four groups: the control group(fed with normal feed for1 month), the HFD group(fed with HFD for 1 month), the T2DM group(HFD combined with STZ and blood glucose ≥11.1 m M), and the unformed T2DM model(Un-mod) group(HFD combined with STZ and blood glucose <11.1 m M). Feces were collected, and bacterial communities in the fecal samples were analyzed by 16S r RNA gene sequencing. The content of short-chain fatty acids(SCFAs) in feces was measured by gas chromatography. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of G protein-coupled receptor 41(GPR41) and GPR43.Results: At different stages of T2DM, the intestinal flora and SCFAs content of rats were significantly decreased(all P <.05). Our results indicated that g__Prevotella had a significant negative correlation, and g__Ruminococcus_torques_group and g__lachnoclastic had a significant positive correlation with blood glucose. The content of SCFAs, in particular acetate and butyrate, in rat feces of different stages of T2DM were significantly reduced, as well as GPR41 and GPR43 expression. The results in the Un-mod group were similar to the T2DM group, and the expression of GPR41 and GPR43 proteins were significantly higher than those in the T2DM group(both P <.001).Conclusion: The intestinal flora-SCFAs-GPR41/GPR43 network may be important in the development of T2DM. Decreasing blood glucose levels by regulating the intestinal flora may become a new therapeutic strategy for T2DM, which has very important clinical and social values.
文摘A 75-year-old male presented with difficult defecationand increasing urinary frequency over a few months. He had a significant history of previous partial gastrectomy for gastric carcinoma 20 years prior. Computed tomography of the abdomen and pelvis showed extensive lymphadenopathy, a gastric mass and rectal as well as bladder wall thickening with bilateral ureterohydronephrosis. Normal looking serosal surfaces of the bladder and bowel were seen on laparoscopy and a defunctioning ileostomy was created. Gastroscopy revealed a malignant mass while cystoscopy and sigmoidscopy found extensive tumour growth lining the mucosal surfaces. Biopsies from all sites were compatible with intestinal type adenocarcinoma of gastric origin with few signet ring cells. Metabolic response to palliative chemotherapy was good and the patient's symptoms have improved on follow-up four months post ileostomy. We discuss the immunohistochemical profile of the tumour and review the literature.
文摘Objective The pathological significance of nitric oxide (NO) in the intestinal type radiation sickness. Methods: The intestinal type radiation sickness of BALB/c mice were induced byCo γ-radiation, andthe nitric oxide synthase (NOS), mucosa structure and survival rate of intestinal gland were examined by using NADPH-diaphorase histochemistry, H-E staining, Feulgen’s reaction and intestinal gland counting techniques. Results: Compared with irradiated mice without (L--NAME ) treatment, the dilatation of intestinalcavity and blood vessels of mice treated with L-NAME were lessened, the survival rates of intestinal glandwere remarkably increased (P < 0. 01), the mucosal structure was obviously improved, and the amount ofNOS--positive structures or products were also reduced. Conclusion: Activation of NOS or increase of NOsynthesis might aggravate the acute pathological injuries of intestines of the irradiated mice, whereas administration of L-NAME has protective effect on the intestinal mucosa to certain extent.