Isletβ-cell function preservation by different anti-diabetic treatments in Chinese elderly patients with type 2 diabetes mellitus

BACKGROUND The preservation of isletβ-cell function in elderly patients with type 2 diabetes mellitus(T2DM)is a top priority for diabetic control.AIM To assess the preservation of isletβ-cell function among elderly Chinese patients with T2DM after different anti-diabetic treatments.METHODS In this longitudinal observational study,elderly patients with T2DM treated with insulin,oral antidiabetic drugs or a combination of both were enrolled to disclose their isletβ-cell function between baseline and follow-up.Isletβ-cell function was determined by the plasma Homeostasis Model forβ-cell function(HOMA-β),Cpeptide and area under the curve(AUC)based on oral glucose tolerance test.Changes inβ-cell function(decrement or increment from baseline)between different therapy groups were the outcomes.RESULTS In total,745 elderly patients(≥60 years)with T2DM[insulin monotherapy,n=105;oral anti-diabetic drugs(OAD)monotherapy,n=321;insulin plus OAD,n=319]had their baseline and follow-upβ-cell function assessed during a median observation period of 4.5 years(range,3.0-7.2 years).Overall,isletβ-cell function(HOMA-β,fasting Cpeptide,fasting insulin,AUCc-pep,AUCins,AUCc-pep/AUCglu,AUCins/AUCglu)consistently deteriorated over time regardless of the three different antidiabetic treatments.No statistical differences in decrement were observed among the three groups regarding the isletβ-cell function indices.All three groups showed an increased ratio of delayed insulin secretion response after 4.5 years of observation.CONCLUSION In Chinese elderly patients with T2DM,isletβ-cell function progressively declines regardless of insulin supplement or insulin plus OAD treatments.

γ-aminobutyric acid secreted from isletβ-cells modulates exocrine secretion in rat pancreas

AIM： To investigate the role of endogenous γ-aminobutyric acid （GABA） in pancreatic exocrine secretion. METHODS： The isolated, vascularly perfused rat pancreas was employed in this study to eliminate the possible influences of extrinsic nerves and hormones. Cholecystokinin （CCK; 10 pmol/L） was intra-arterially given to stimulate exocrine secretion of the pancreas. RESULTS： Glutamine, a major precursor of GABA, which was given intra-arterially at concentrations of 1, 4 and 10 mmol/L, dose-dependently elevated the CCK-stimulated secretions of fluid and amylase in the normal pancreas. Bicuculline （10 μmol/L）, a GABAA receptor antagonist, blocked the enhancing effect of glutamine （4 mmol/L） on the CCK-stimulated exocrine secretions. Glutamine, at concentrations of 1, 4 and 10 mmol/L, dose-dependently increased the GABA concentration in portal effluent of the normal pancreas. The effects of glutamine on the CCK-stimulated exocrine secretion as well as the GABA secretion were markedly reduced in the streptozotocintreated pancreas. CONCLUSION： GABA could be secreted from β-cells into the isletoacinar portal system after administration of glutainine, and could enhance the CCK-stimulated exocrine secretion through GABAA receptors. Thus, GABA in islet β-cells is a hormone modulating pancreatic exocrine secretion.

Huanglian-Renshen-Decoction Maintains Isletβ-Cell Identity in T2DM Mice through Regulating GLP-1 and GLP-1R in Both Islet and Intestine

To elucidate the effect of Huanglian-Renshen-Decoction(HRD)on ameliorating type 2 diabetes mellitus by maintaining isletβ-cell identity through regulating paracrine and endocrine glucagon-like peptide-1(GLP-1)/GLP-1 receptor(GLP-1R)in both islet and intestine.Methods The db/db mice were divided into the model(distilled water),low-dose HRD(LHRD,3 g/kg),high-dose HRD(HHRD,6 g/kg),and liraglutide(400µg/kg)groups using a random number table,8 mice in each group.The db/m mice were used as the control group(n=8,distilled water).The entire treatment of mice lasted for 6 weeks.Blood insulin,glucose,and GLP-1 levels were quantified using enzyme-linked immunosorbent assay kits.The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry(IHC)and immunofluorescence(IF)staining.Then,GLP-1,GLP-1R,prohormone convertase 1/3(PC1/3),PC2,v-maf musculoaponeurotic fibrosarcoma oncogene homologue A(MafA),and pancreatic and duodenal homeobox 1(PDX1)were detected by Western blot,IHC,IF,and real-time quantitative polymerase chain reaction,respectively.Results HRD reduced the weight and blood glucose of the db/db mice,and improved insulin sensitivity at the same time(P<0.05 or P<0.01).HRD also promoted mice to secrete more insulin and less glucagon(P<0.05 or P<0.01).Moreover,it also increased the number of isletβcell and decreased isletαcell mass(P<0.01).After HRD treatment,the levels of GLP-1,GLP-1R,PC1/3,PC2,MafA,and PDX1 in the pancreas and intestine significantly increased(P<0.05 or P<0.01).Conclusion HRD can maintain the normal function and identity of isletβcell,and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.

2型糖尿病合并亚临床甲状腺功能减退症患者HOMA-IR HOMA-ISLET与TSH水平的关系研究

目的:探究2型糖尿病合并亚临床甲状腺功能减退症(甲减)患者的胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-ISLET)与促甲状腺激素(TSH)水平的关系。方法:选取102例在我院治疗的2型糖尿病合并亚临床甲减患者,收治时间为2019年10月至2024年10月,根据TSH水平分为正常组(n=49)和升高组(n=53),正常组:TSH(0.3-3.6)mIU/L,升高组:TSH>3.6mIU/L。收集两组患者的基本资料,检测所有患者血糖指标,计算HOMA-IR、HOMA-ISLET值。比较两组基本资料、HOMA-IR、HOMA-ISLET水平;采用Spearman法分析HOMA-IR、HOMA-ISLET与TSH水平的相关性;ROC曲线分析HOMA-IR、HOMA-ISLET对TSH水平的预测价值。结果:两组基本资料比较差异无统计学意义,具有可比性(P>0.05);与正常组相比,升高组HOMA-IR水平更高,HOMA-ISLET水平更高(P<0.05);HOMA-IR、HOMA-ISLET与TSH水平呈正相关(P<0.05);ROC曲线分析显示,HOMA-IR对TSH升高的预测特异度高,HOMA-ISLET的曲线下面积和灵敏度高。结论:2型糖尿病合并亚临床甲减患者HOMA-IR、HOMA-ISLET与TSH水平呈正相关,HOMA-IR、HOMA-ISLET对TSH升高具有一定的预测价值,HOMA-ISLET的预测效能更高。

Relationship between imaging changes of the pancreas and islet beta-cell function

Imaging changes in the pancreas can provide valuable information about the status of islet beta-cell function in different pancreatic diseases,such as diabetes,pancreatitis,pancreatic cancer,fatty pancreas,and insulinoma.While imaging cannot directly measure beta-cell function;it can be used as a marker of disease progression and a tool to guide therapeutic interventions.As imaging techno-logies continue to advance,they will likely play an increasingly important role in diagnosing,monitoring,and managing diabetes.

Plantamajoside improves type 2 diabetes mellitus pancreaticβ-cell damage by inhibiting endoplasmic reticulum stress through Dnajc1 up-regulation

BACKGROUND Plantamajoside(PMS)has shown potential in mitigating cell damage caused by high glucose(HG)levels.Despite this,the precise therapeutic effects of PMS on type 2 diabetes mellitus(T2DM)and the underlying regulatory mechanisms require further exploration.AIM To investigate PMS therapeutic effects on T2DM in mice and elucidate its mechanisms of action through in vivo and in vitro experiments.METHODS An in vitro damage model of MIN6 cells was established using HG and palmitic acid(PA).PMS's protective effect on cell damage was assessed.Next,transcriptomics was employed to examine how PMS treatment affects gene expression of MIN6 cells.Furthermore,the effect of PMS on protein processing in endoplasmic reticulum and apoptosis pathways was validated.A T2DM mouse model was used to validate the therapeutic effects and mechanisms of PMS in vivo.RESULTS PMS intervention ameliorated cell injury in HG+PA-induced MIN6 cell damage.Transcriptomic analysis revealed that protein processing in the endoplasmic reticulum and apoptosis pathways were enriched in cells treated with PMS,with significant downregulation of the gene Dnajc1.Further validation indicated that PMS significantly inhibited the expression of apoptosis-related factors(Bax,CytC)and endoplasmic reticulum stress(ERS)-related factors[ATF6,XBP1,Ddit3(CHOP),GRP78],while promoting the expression of Bcl-2 and Dnajc1.Additionally,the inhibitory effects of PMS on ERS and apoptosis were abolished upon Dnajc1 silencing.Furthermore,in vivo experiments demonstrated that PMS intervention effectively improved pancreatic damage,suppressed the expression of apoptosis-related factors(Bax,CytC),and ERS-related factors[ATF6,XBP1,Ddit3(CHOP),GRP78],while promoting the expression of Bcl-2 and Dnajc1 in a T2DM model mice.CONCLUSION PMS intervention could alleviate pancreatic tissue damage effectively.The mechanism of action involves Dnajc1 activation,which subsequently inhibits apoptosis and ERS,ameliorating damage to pancreaticβ-cells.

Fentanyl inhibits glucose-stimulated insulin release from β-cells in rat pancreatic islets

AIM： TO explore the effects of fentanyl on insulin release from freshly isolated rat pancreatic islets in static culture. METHODS： Islets were isolated from the pancreas of mature Sprague Dawley rats by common bile duct intraductal collagenase V digestion and were purified by discontinuous Ficoll density gradient centrifugation. The islets were divided into four groups according to the fentanyl concentration： control group （0 ng/mL）, group I （0.3 ng/mL）, group I （3.0 ng/mL）, and group III （30 ng/mL）. In each group, the islets were co-cultured for 48 h with drugs under static conditions with fentanyl alone, fentanyl ＋ 0.1 μg/mL naloxone or fentanyl ＋ 1.0 μg/mL naloxone. Cell viability was assessed by the MTT assay. Insulin release in response to low and high concentrations （2.8 mmol/L and 16.7 mmol/L, respectively） of glucose was investigated and electron microscopy morphological assessment was performed. RESULTS： Low- and high-glucose-stimulated insulin release in the control group was significantly higher than in groups I and II （62.33 ± 9.67 μIU vs 47.75 ± 8.47 μIU, 39.67 ± 6.18 μIU and 125.5 ± 22.04 μIU vs 96.17 ± 14.17 μIU, 75.17 ± 13.57 μIU, respectively, P 〈 0.01） and was lowest in group III （P 〈 0.01）. After adding 1 μg/mL naloxone, insulin release in groups II and II was not different from the control group. Electron microscopy studies showed that the islets were damaged by 30 ng/ml fentanyl. CONCLUSION： Fentanyl inhibited glucose-stimulated insulin release from rat islets, which could be prevented by naloxone. Higher concentrations of fentanyl significantly damaged β-cells of rat islets.

Intra-islet endothelial cell and β-cell crosstalk: Implication for islet cell transplantation

The intra-islet microvasculature is a critical interface between the blood and islet endocrine cells governing a number of cellular and pathophysiological processes associated with the pancreatic tissue. A growing body of evidence indicates a strong functional and physical interdependency of β-cells with endothelial cells(ECs), the building blocks of islet microvasculature. Intra-islet ECs, actively regulate vascular permeability and appear to play a role in fine-tuning blood glucose sensing and regulation. These cells also tend to behave as "guardians", controlling the expression and movement of a number of important immune mediators, thereby strongly contributing to the physiology of islets. This review will focus on the molecular signalling and crosstalk between the intra-islet ECs and β-cells and how their relationship can be a potential target for intervention strategies in islet pathology and islet transplantation.

Relationship between Free Thyroxine and Islet Beta-cell Function in Euthyroid Subjects

Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and non-treated type 2 diabetes mellitus(T2DM)patients.A total of 5089 euthyroid participants(including 4601 general population and 488 non-treated T2DM patients)were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016.Anthropometric indices,biochemical parameters,and thyroid hormones were measured.Compared with general population,non-treated T2DM patients exhibited higher total thyroxine(TT4)and free thyroxine(FT4)levels but lower ratio of free triiodothyronine(T3):T4(P<0.01).HOMA-βhad prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age,body mass index(BMI)and smoking.When analyzed by quartiles of FT4 or free T3:T4,there were significantly decreased trend of HOMA-β going with the higher FT4 and lower free T3:T4 in both groups.Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-β no matter in general population or T2DM patients,which was independent of age,BMI,smoking,hypertension and lipid profiles.FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects.Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.

Implanting 1.1B4 human β-cell pseudoislets improves glycaemic control in diabetic severe combined immune deficient mice

AIM To investigate the potential of implanting pseudoislets formed from human insulin-releasing β-cell lines as an alternative to islet transplantation. METHODS In this study, the anti-diabetic potential of novel human insulin releasing 1.1B4 β-cells was evaluated by implanting the cells, either as free cell suspensions, or as three-dimensional pseudoislets, into the subscapular region of severe combined immune deficient mice rendered diabetic by single high-dose administration of streptozotocin. Metabolic parameters including food and fluid intake, bodyweight and blood glucose were monitored throughout the study. At the end of the study animals were given an intraperitoneal glucosetolerance test. Animals were then culled and blood and tissues were collected for analysis. Insulin and glucagon contents of plasma and tissues were measured by insulin radioimmunoassay and chemiluminescent enzyme-linked immunosorbance assay respectively. Histological analyses of pancreatic islets were carried out by quantitative fluorescence immunohistochemistry staining. RESULTS Both pseudoislet and cell suspension implants yielded well vascularised β-cell masses of similar insulin content. This was associated with progressive amelioration of hyperphagia(P < 0.05), polydipsia(P < 0.05), body weight loss(P < 0.05), hypoinsulinaemia(P < 0.05), hyperglycaemia(P < 0.05- P < 0.001) and glucose tolerance(P < 0.01). Islet morphology was also significantly improved in both groups of transplanted mice, with increased β-cell(P < 0.05- P < 0.001) and decreased alpha cell(P < 0.05- P < 0.001) areas. Whereas mice receiving 1.1B4 cell suspensions eventually exhibited hypoglycaemic complications, pseudoislet recipients displayed a more gradual amelioration of diabetes, and achieved stable blood glucose control similar to non-diabetic mice at the end of the study. CONCLUSION Although further work is needed to address safety issues, these results provide proof of concept for possible therapeutic applicability of human β-cell line pseudoislets in diabetes.

Circulating exosome-like vesicles of humans with nondiabetic obesity impaired isletβ-cell proliferation,which was associated with decreased Omentin-1 protein cargo

The regulation ofβ-cell mass in the status of nondiabetic obesity remains not well understood.We aimed to investigate the role of circulating exosome-like vesicles(ELVs)isolated from humans with simple obesity in the regulation of isletβ-cell mass.Between June 2017 and July 2019,81 subjects with simple obesity and 102 healthy volunteers with normal weight were recruited.ELVs were isolated by ultra-centrifugation.The proliferations ofβ-cells and islets were measured by 5-ethynl-2′-deoxyuridine(EdU).Protein components in ELVs were identified by Quantitative Proteomic Analysis and verified by Western blot and ELISA.The role of specific exosomal protein was analyzed by gain-of-function approach in ELVs released by 3T3-L1 preadipocytes.Circulating ELVs from subjects with simple obesity inhibitedβ-cell proliferation in vitro without affecting its apoptosis,secretion,and inflammation.The protein levels of Rictor and Omentin-1 were downregulated in circulating ELVs from subjects with simple obesity and associated with the obesity-linked pathologic conditions.The ELV-carried Omentin-1 and Omentin-1 protein per se were validated to increaseβ-cell proliferation and activate Akt signaling pathway.Moreover,Omentin-1 in ELVs was downregulated by insulin.The circulating ELVs may act as a negative regulator forβ-cell mass in nondiabetic obesity through inhibitingβ-cell proliferation.This effect was associated with downregulated Omentin-1 protein in ELVs.This newly identified ELV-carried protein could be a mediator linking insulin resistance to impairedβ-cell proliferation and a new potential target for increasingβ-cell mass in obesity and T2DM.

1.3 GHz 9-cell高性能超导腔高阶模耦合器电磁及热分析研究

中国科学院高能物理研究所于2023年6月完成了高品质因数1.3 GHz超导加速模组研发,在国际上率先实现了中温退火高品质因数超导腔模组技术路线。模组中集成了八只经过中温退火工艺处理的1.3 GHz9-cell超导腔,在模组的测试过程中超导腔的高阶模耦合器温升异常,导致超导腔无法在高梯度下稳定工作。通过HFSS软件和CST软件中的微波仿真模块对高阶模耦合器进行电磁分析,再通过理论和Ansys Workbench软件对高阶模耦合器进行热仿真分析,并结合模组的高功率实验,找到了超导腔性能异常的原因,并对超导腔高阶模耦合器的冷却方式进行了进一步的优化,解决了模组中超导腔高梯度下的不稳定性。

Regeneration of islet β-cells in tree shrews and rats

Backgroud: Current understanding of injury and regeneration of islet β-cells in diabetes is mainly based on rodent studies. The tree shrew is now generally accepted as being among the closest living relatives of primates, and has been widely used in animal experimentation. However, there are few reports on islet cell composition and regeneration of β-cells in tree shrews.Methods: In this study, we examined the changes in islet cell composition and regeneration of β-cells after streptozotocin(STZ) treatment in tree shrews compared with Sprague-Dawley rats. Injury and regeneration of islet β-cells were observed using hematoxylin and eosin(HE) staining and immunohistochemical staining for insulin, glucagon, somatostatin and PDX-1.Results: Our data showed that in rats islet injury was most obvious on day 3 after injection, and islet morphologies were significantly restored by day 21. Regeneration of islet β-cells was very pronounced in rats, and mainly involved regeneration of centro-acinar cells and transformation of extra-islet ductal cells. In tree shrews, the regeneration of islet β-cells was not as significant. On days 3 and 7, only scattered regenerated cells were observed in the remaining islets. Further, no regeneration of centro-acinar cells was observed.Conclusion: The results suggest that the repair mechanism of islet β-cells in tree shrews is similar to that of humans.

Upregulation of α-ENaC induces pancreatic β-cell dysfunction,ER stress,and SIRT2 degradation

Islet beta cells(β-cells)produce insulin in response to high blood glucose levels,which is essential for preserving glucose homeostasis.Voltage-gated ion channels inβ-cells,including Na+,K+,and Ca2+channels,aid in the release of insulin.The epithelial sodium channel alpha subunit(α-ENaC),a voltage-independent sodium ion channel,is also expressed in human pancreatic endocrine cells.However,there is no reported study on the function of ENaC in theβ-cells.In the current study,we found thatα-ENaC was expressed in human pancreatic glandule and pancreatic isletβ-cells.In the pancreas of db/db mice and high-fat diet-induced mice,and in mouse isletβ-cells(MIN6 cells)treated with palmitate,α-ENaC expression was increased.Whenα-ENaC was overexpressed in MIN6 cells,insulin content and glucose-induced insulin secretion were significantly reduced.On the other hand,palmitate injured isletβ-cells and suppressed insulin synthesis and secretion,but increasedα-ENaC expression in MIN6 cells.However,α-ENaC knockout(Scnn1a−/−)in MIN6 cells attenuatedβ-cell disorder induced by palmitate.Furthermore,α-ENaC regulated the ubiquitylation and degradation of sirtuin 2 inβ-cells.α-ENaC also modulatedβ-cell function in correlation with the inositol-requiring enzyme 1 alpha/X-box binding protein 1(IRE1α/XBP1)and protein kinase RNA-like endoplasmic reticulum kinase/C/EBP homologous protein(PERK/CHOP)endoplasmic reticulum stress pathways.These results suggest thatα-ENaC may play a novel role in insulin synthesis and secretion in theβ-cells,and the upregulation ofα-ENaC promotes isletβ-cell dysfunction.In conclusion,α-ENaC may be a key regulator involved in isletβ-cell damage and a potential therapeutic target for type 2 diabetes mellitus.

Insufficient TRPM5 Mediates Lipotoxicity-induced Pancreaticβ-cell Dysfunction

Objective:While the reduction of transient receptor potential channel subfamily M member 5(TRPM5)has been reported in islet cells from type 2 diabetic(T2D)mouse models,its role in lipotoxicity-induced pancreaticβ-cell dysfunction remains unclear.This study aims to study its role.Methods:Pancreas slices were prepared from mice subjected to a high-fat-diet(HFD)at different time points,and TRPM5 expression in the pancreaticβcells was examined using immunofluorescence staining.Glucose-stimulated insulin secretion(GSIS)defects caused by lipotoxicity were mimicked by saturated fatty acid palmitate(Palm).Primary mouse islets and mouse insulinoma MIN6 cells were treated with Palm,and the TRPM5 expression was detected using qRT-PCR and Western blotting.Palm-induced GSIS defects were measured following siRNA-based Trpm5 knockdown.The detrimental effects of Palm on primary mouse islets were also assessed after overexpressing Trpm5 via an adenovirus-derived Trpm5(Ad-Trpm5).Results:HFD feeding decreased the mRNA levels and protein expression of TRPM5 in mouse pancreatic islets.Palm reduced TRPM5 protein expression in a time-and dose-dependent manner in MIN6 cells.Palm also inhibited TRPM5 expression in primary mouse islets.Knockdown of Trpm5 inhibited insulin secretion upon high glucose stimulation but had little effect on insulin biosynthesis.Overexpression of Trpm5 reversed Palm-induced GSIS defects and the production of functional maturation molecules unique toβcells.Conclusion:Our findings suggest that lipotoxicity inhibits TRPM5 expression in pancreaticβcells both in vivo and in vitro and,in turn,drivesβ-cell dysfunction.

Dietary Green Tea Extract and Antioxidants Improve Insulin Secretory Functions of Pancreatic β-Cells in Mild and Severe Experimental Rodent Model of Chronic Pancreatitis

Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (EGCG) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EGCG dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EGCG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EGCG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.

The Effect of Tuberculosis Infection on Pancreatic Beta-Cell Function in Patients with Type 2 Diabetes Mellitus

Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The study group consisted of 89 patients with type 2 diabetes mellitus and tuberculosis infection who were admitted to Jingzhou Chest Hospital between March 2019 and March 2021. Gender and duration of diabetes were matching conditions. The control group was made up of 89 patients with type 2 diabetes who were admitted to Jingzhou Central Hospital’s endocrinology department during the same period. The two patient groups provided general information such as gender, age, length of diabetes, and blood biochemical indexes such as glycosylated hemoglobin (HbA1c), fasting glucose (FPG), and fasting C-peptide (FC-P). The HOMA calculator was used to calculate the HOMA-β and the HOMA-IR, and intergroup comparisons and correlation analyses were carried out. Results: Regarding gender, age, disease duration, FC-P, and HbA1c, the differences between the two groups were not statistically significant (P > 0.05). However, BMI, FPG, HOMA-β, and HOMA-IR showed statistically significant differences (P < 0.05). In comparison to the control group, the study group’s HOMA-β was lower and its HOMA-IR was greater. According to Spearman’s correlation analysis, HOMA-β had a negative association (P th FPG, HbA1c, and the length of the disease, and a positive correlation with BMI and FC-P. A positive correlation was found between HOMA-IR and BMI, FPG, and FC-P (P < 0.01), as well as a correlation with the length of the disease (P > 0.05) and HbA1c. Conclusions: In type 2 diabetes mellitus combined with tuberculosis infection, the patients had higher FPG levels and lower FC-P levels, the secretory function of pancreatic β-cells was more severely impaired, and insulin resistance was more obvious.

Mannogalactoglucan from mushrooms protects pancreatic islets via restoring UPR and promotes insulin secretion in TIDM mice

Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.

μ-cell法测定农药对男性精子机能影响的分析

目的研究农药对生育生殖的影响。方法采用μ－ｃｅｌ测定方法。结果暴露组精子的质量与数量都受到了影响，均呈下降趋势。结论长期暴露于农药污染，可能引起生育生殖功能的下降。

小鼠Islet-1基因慢病毒表达载体的构建及其诱导C_3H_(10)T1/2细胞向心肌样细胞特异性分化

目的研究Islet-1对干细胞分化的影响。方法用PCR钓取目的基因,将目的基因与pLenO-WPI载体连接,选取阳性质粒,与辅助质粒共同感染293T细胞生产出慢病毒载体。感染C3H10T1/2细胞,实时荧光定量PCR及Western blot检测Islet-1和心肌、肝脏、骨骼及神经各系统相关标志物的表达,免疫荧光检测心肌肌钙蛋白T(cTnT)表达部位。结果 PCR及测序显示目的片段正确插入,实验组有Islet-1表达;心肌早期发育相关基因GATA-4、MEF2C、NKx2.5在检测到荧光蛋白1周后升高,2周到达高峰,3周后可检测到心肌特异性蛋白cTnT(0.582±0.0576),其时序性表达呈随时间增强趋势;cTnT表达于胞质;肝脏系统特异性标志AFP及ALB、骨骼系统特异性标志BGP及BALP、神经系统特异性标志Nestin及GFAP均未表达。结论 Islet-1具有特异性促进干细胞向心肌样细胞分化的作用。