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.

Epinephrine also acts on beta cells and insulin secretion

In a recent review examining neurotransmitter modulation of insulin secretion,the significant impact of epinephrine was not addressed.Its primary action involves inhibiting insulin release via alpha-adrenergic receptors,thereby reducing the response to insulin secretion stimulators,through the activation of K+channels and resulting in membrane hyperpolarization in beta cells.

Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion

BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass(DJB)surgery is not clear.AIM To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model.METHODS DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model.All adipose tissue was weighed and observed under microscope.Use inguinal fat to represent subcutaneous adipose tissue(SAT)and mesangial fat to represent visceral adipose tissue.RNA-sequencing was utilized to evaluate gene expression alterations adipocytes.The hematoxylin and eosin staining,reverse transcription-quantitative polymerase chain reaction,western blot,and enzyme-linked immunosorbent assay were used to study the changes.Insulin resistance was evaluated by immunofluorescence.RESULTS After DJB,whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved.Fat cell volume in both visceral adipose tissue(VAT)and SAT increased.Compared to SAT,VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone(GH)pathway and downstream adiponectin secretion were involved in metabolic regulation.The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased.Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity.CONCLUSION GH improves insulin resistance in VAT in male diabetic rats after receiving DJB,possibly by increasing adiponectin secretion.

The Effect of Umami Stimulation on Salivary Secretion Rate and Duration

Purpose: Umami reportedly promotes salivation. We aimed to investigate the effects of taste stimuli on slow and fast salivary secretion in humans using umami, sweet, and sour stimuli. Methods: Eight healthy women participated between 14:00 and 15:00, taking the circadian rhythm of salivary secretion into account. The types and concentrations of the taste solutions were glutamic acid (1.7 × 10−3 M), inosinic acid (9.8 × 10−3 M), and guanylic acid (9.8 × 10−3 M) for umami stimulation, citric acid (6.5 × 10−3 M) for acidity stimulation, and sucrose (1.6 × 10−2 M) for sweetness stimulation. First, the unstimulated salivary flow rate was measured. Then, 3 ml of a flavor solution was dropped under the tongue using a syringe. The saliva was expelled into an aluminum cup every minute and weighed. The first minute’s value minus 3 ml flavor solution was the stimulated salivary secretion rate produced by each flavor. The time-to-return to the initial unstimulated salivary flow rate was the duration of the stimulated saliva secretion rate. Results: The mean unstimulated salivary flow rate across participants was 0.64 ± 0.25 ml/min (range: 0.23 - 1.03 ml/min). The highest amount of saliva was induced by citric acid. There were significant differences between citric acid and the other flavor solutions (p < 0.05 for glutamic acid, inosinic acid, and sucrose;p < 0.01 for guanylic acid). There were no significant differences in duration of salivation between the flavor solutions. When the participants were divided into slow (0.45 ± 0.16 ml/min) and fast groups (0.83 ± 0.15 ml/min) based on their median resting salivary secretion rate, there were no significant differences between the two groups in the amount of saliva secreted at 1 minute after stimulation and the duration of the salivary secretion rate. Conclusion: Umami stimulation was effective in slowing salivary secretion and sustaining salivary secretion after stimulation.

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.

Neurotransmitters regulateβcells insulin secretion:A neglected factor

βcells are the main cells responsible for the hypoglycemic function of pancreatic islets,and the insulin secreted by these cells is the only hormone that lowers blood glucose levels in the human body.βcells are regulated by various factors,among which neurotransmitters make an important contribution.This paper discusses the effects of neurotransmitters secreted by various sympathetic and parasympathetic nerves onβcells and summarizes the mechanisms by which various neurotransmitters regulate insulin secretion.Many neurotransmitters do not have a single source and are not only released from nerve terminals but also synthesized byβcells themselves,allowing them to synergistically regulate insulin secretion.Almost all of these neurotransmitters depend on the presence of glucose to function,and their actions are mostly related to the Ca^(2+)and cAMP concentrations.Although neurotransmitters have been extensively studied,many of their mechanisms remain unclear and require further exploration by researchers.

Vitamin D, Parathyroid Hormone, Insulin Sensitivity and Islet β-Cell Secretory Function in Diabetic Patients from South Kivu in the Democratic Republic of Congo: Cross-Sectional Study

Background: The role of vitamin D and parathyroid hormone in the metabolic profile of type 2 diabetes mellitus in sub-Saharan Africa has not been adequately assessed. The aim of this study was to determine the prevalence of low vitamin D level and secondary hyperparathyroidism and their association with insulin sensitivity and β-cell secretory function among Congolese type 2 diabetics. Methodology: Fasting glycaemia, fasting insulin, 25OH D3 and human parathyroid hormone (hPTH) were measured in one hundred and eighty-four type 2 diabetic patients followed as outpatients in South Kivu. Levels of 25OH D3 65 pg/ml defined low vitamin D and elevated parathyroid hormone levels, respectively. The HOMA model was used to measure insulin sensitivity and β-cell secretory function. Results: Medians (IQR) were 25.3 (20.4 - 32.4) ng/ml for 25OH D3 and 53.7 (38.4 - 115.7) pg/ml for hPTH. 58.7% of diabetics had insulin resistance, 126 (68.5%) had low vitamin D and 80 (43.5%) had hyperparathyroidism. In multivariate analysis, hPTH (partial r = −0.28;p = 0.0002) and 25OH D3 (partial r = 0.16;p = 0.03) showed an independent association with insulin sensitivity after adjustment for body mass index and waist circumference. Finally, hPTH (partial r = 0.27;p = 0.0002) was the sole determinant of β-cell secretory function. Conclusions: This study confirms the high prevalence of low vitamin D level and secondary hyperparathyroidism and their association with insulin resistance and impaired islet β-cell secretory function among Congolese with type 2 diabetes mellitus. Vitamin D and calcium supplementation should be envisaged for cases of deficiency in this region.

Role of selenium in type 2 diabetes,insulin resistance and insulin secretion

Selenium is a trace mineral essential for life that acts physiologically through selenoproteins.Among other actions,the endogenous antioxidant selenoprotein glutathione peroxidase and the selenium transporter in blood,selenoprotein P,seem to play an important role in type 2 diabetes mellitus and insulin resistance by weakening the insulin signaling cascade through different mechanisms.Recent findings also suggest that selenoproteins also affect insulin biosynthesis and insulin secretion.This review discussed the role of selenium in type 2 diabetes and the complex interplay between selenoproteins and insulin pathways.

Short-Term Effects of Liraglutide versus Vildagliptin on Insulin Secretion and Sensitivity in Type 2 Diabetes: A Single Blinded Randomized Controlled Trial (LIRAVIS Study)

Background: We aimed to evaluate the short-term metabolic effects of a GLP-1a, (liraglutide) versus a DPP-4i, (vildagliptin) in a group of sub-Saharan type 2 diabetes patients. Methods: We conducted a randomized controlled single blinded clinical trial in 14 uncontrolled type 2 diabetes patients (HbA1c ≥ 53 mmol/mol) with mean duration of diabetes of 8 [1 - 12] years and median age of 57 [49 - 61] years. Baseline treatment consisted of metformin in monotherapy or metformin plus sulfonylureas. Participants were randomly allocated to 2 groups of add-on 1.2 mg/day subcutaneous liraglutide in group 1 or 100 mg/day of oral vildagliptin in group 2 for 2 weeks. In all participants, insulin secretion in response to mixed meal tolerance test, insulin sensitivity by 80 mU/m2/min hyperinsulinemic-euglycemic clamp, body composition, and lipid profile were measured before and after intervention. Results: At the end of intervention, insulin sensitivity remained unchanged both with liraglutide from 6.6 [4.2 - 7.9] to 6.9 [4.3 - 10.8] mg/kg/min;p = 0.61 and vildagliptin from 7.1 [5.3 - 9.0] to 6.5 [5.6 - 9.4] mg/kg/min (p = 0.86). The area under the C-peptide curve varied from 5.5 [1.0 - 10.9] to 14.9 [10.8 - 17.2] nmol/L/120min, p = 0.09 in group 1 and from 1.1 [0.5 - 14.1] to 13.0 [9.6 - 16.9] nmol/L/120min (p = 0.17) in group 2. LDL Cholesterol levels decreased significantly with liraglutide from 0.85 g/L [0.51 - 1.02] to 0.54 g/L [0.50 - 0.73] (p = 0.04) but not with Vildagliptin. Body weight tended to decrease in group 1 (−0.6 kg) versus modest increase in group 2 (+1.1 kg). Conclusion: Short-term metabolic effects of Liraglutide and Vildagliptin add-on therapy are comparable in sub-Saharan type 2 diabetes patients with a more favorable trend for Liraglutide on body weight, lipid profile, and insulin secretion.

Vascular endothelial growth factor B improves impaired glucose tolerance through insulin-mediated inhibition of glucagon secretion

BACKGROUND Impaired glucose tolerance(IGT)is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes.When IGT occurs,insulin sensitivity decreases,causing a reduction in insulin secretion and an increase in glucagon secretion.Recently,vascular endothelial growth factor B(VEGFB)has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity.Therefore,we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion,thus contributing to the prevention and cure of prediabetes.AIM To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT.METHODS We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression.Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay,and the protein expression of phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)was determined using western blot.Further,mRNA expression of forkhead box protein O1,phosphoenolpyruvate carboxykinase,and glucose-6 phosphatase was detected via quantitative polymerase chain reaction,and the correlation between the expression of proteins was analyzed via bioinformatics.RESULTS In mice with IGT and VEGFB knockout,glucagon secretion increased,and the protein expression of PI3K/AKT decreased dramatically.Further,in mice with VEGFB overexpression,glucagon levels declined,with the activation of the PI3K/AKT signaling pathway.CONCLUSION VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.

Long-Term Persistent Absolute Insulin Secretion Deficiency in Diabetes Induced by Immune Checkpoint Inhibitors

Immune checkpoint inhibitors are today an immense hope in the management of cancers. However, since their widespread use, many cases of insulin-requiring diabetes appearing suddenly, as fulminant diabetes have been reported. Here, we describe 4 cases that occurred at different times after the beginning of immune checkpoint inhibitor therapy with Nivolumab alone or associated with Ipilimumab. There are 3 cases of newly diagnosed diabetes and 1 case of known type 2 diabetes formerly quite well balanced with Metformin. The clinical and biological characteristics of these patients are quite similar. They were all insulin-requiring at the discovery of diabetes and remained so throughout their follow-up. This type of diabetes which looks like type 1 diabetes seems rather to be a new entity.

Anti-diabetic effects of Caulerpa lentillifera:stimulation of insulin secretion in pancreatic β-cells and enhancement of glucose uptake in adipocytes

Objective:To evaluate anti-diabetic effect of Caulrpa kntillifera(C.lentillifera).Methods:The inhibitory effect of C.lentillifera extract on dipeptidyl peptidase-IV and a-glucosidase enzyme was measured in a cell free system.Then,interleukin-1βand interferon-γinduced cell death and insulin secretion were measured in rat insulinoma(RIN)cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ELISA kit,respectively.Glucose uptake and glucose transporter expression were measured by fluorometry and western blotting,using 3T3-Ll adipocytes.Results:C.lentillifera extract significantly decreased dipeptidyl peptidase-IV and a-glucosidase enzyme activities,and effectively inhibited cell death and iNOS expression in interleukin-1βand interfcron-γinduced RIK cells.Furthermore,C.lntillifera extract significantly enhanced insulin secretion in RTN cells and glucose transporter expression and glucose uptake in 3T3-L1adipocytes.Conclusions:Thus,our results suggest that C.lentillifera could be used as a potential antidiabetic agenl.

Roles of sulfonylurea receptor 1 and multidrug resistance protein 1 in modulating insulin secretion in human insulinoma

BACKGROUND:Sulfonylurea receptor 1(SUR1)and multidrug resistance protein 1(MRP1)are two prominent members of multidrug resistance proteins associated with insulin secretion. The aims of this study were to investigate their expression in insulinomas and their sole and synergistic effects in modulating abnormal insulin secretion. METHODS:Fasting glucose,insulin and C-peptide were measured in 11 insulinoma patients and 11 healthy controls. Prolonged oral glucose tolerance tests were performed in 6 insulinoma patients.Insulin content,SUR1 and MRP1 were detected in 11 insulinoma patients by immunohistochemistry. SUR1 and MRP1 were also detected in 6 insulinoma patients by immunofluorescence. RESULTS:Insulinoma patients presented the typical demons-trations of Whipple’s triad.Fasting glucose of each insulinoma patient was lower than 2.8 mmol/L,and simultaneous insulin and C-peptide were increased in insulinoma patients. Prolonged oral glucose tolerance tests showed that insulin secretion in insulinoma patients were also stimulated by high glucose.Immunohistochemistry and immunofluorescence staining showed that SUR1 increased,but MRP1 decreased in insulinoma compared with the adjacent islets. CONCLUSIONS:The hypersecretion of insulin in insulinomas might be,at least partially,due to the enrichment of SUR1. In contrast,MRP1,which is down-regulated in insulinomas, might reflect a negative feedback in insulin secretion.

Early postprandial Insulin secretion: Its relation to Insulin sensitivity

Background: Lack of first phase insulin secretion during oral glucose tolerance test [OGTT] in Type 2 Diabetes Mellitus (DM) is attributed to glucose toxicity. Alternatively, the role of insulin resistance in impaired insulin release secondary to lack of glucose entry into β cells may be responsible, but is not examined. Aim: The role of insulin sensitivity in 1st phase insulin secretion was assessed. Material and Methods: Plasma glucose (G) and insulin (I) concentrations were determined after an overnight fast (F) and upto 60 minutes during OGTT with glucose 75g in 12 normal (N), 14 with impaired glucose tolerance (IGT) and 41 subjects with Type 2 DM. First phase insulin secretion (Δ Insulin) was determined as a percentage rise from baseline 100x (Peak-Basal)/Basal. Insulin sensitivity was determined as FI x FG (mUxmM/L). Results: FG were normal (7.0 mM/L in Type 2 DM. FI x FG and ? insulin were 35 ± 4 and 389 ± 89% in N;77 ± 5 and 254 ± 65% in IGT;and 235 ± 19 and 95 ± 15% in Type 2 DM. Significant negative correlations were noted between ? insulin one hand and FI x FG on the other amongst all subjects [p < 0.0001 for all correlations]. Conclusion: Decline of 1st phase insulin secretion in IGT and Type 2 DM may be attributed to inhibited release of depleted insulin stores in the β Cells induced by impaired glucose entry due to insulin resistance, and is unlikely to be caused by glucose toxicity in IGT in presence of fasting euglycemia.

Vascular endothelial growth factor B inhibits insulin secretion in MIN6 cells and reduces Ca2+ and cyclic adenosine monophosphate levels through PI3K/AKT pathway

BACKGROUND Type 2 diabetes(T2 D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance,resulting in an increase in blood glucose.However,the mechanism involved in this lack of insulin secretion is unclear.The level of vascular endothelial growth factor B(VEGF-B) is significantly increased in T2 D patients.The inactivation of VEGF-B could restore insulin sensitivity in db/db mice by reducing fatty acid accumulation.It is speculated that VEGF-B is related to pancreatic β-cell dysfunction and is an important factor affecting β-cell secretion of insulin.As an in vitro model of normal pancreatic β-cells,the MIN6 cell line can be used to analyze the mechanism of insulin secretion and related biological effects.AIM To study the role of VEGF-B in the insulin secretion signaling pathway in MIN6 cells and explore the effect of VEGF-B on blood glucose regulation.METHODS The MIN6 mouse pancreatic islet β-cell line was used as the model system.By administering exogenous VEGF-B protein or knocking down VEGF-B expression in MIN6 cells,we examined the effects of VEGF-B on insulin secretion,Ca2+ and cyclic adenosine monophosphate(cAMP) levels,and the insulin secretion signaling pathway.RESULTS Exogenous VEGF-B inhibited the secretion of insulin and simultaneously reduced the levels of Ca2+ and cAMP in MIN6 cells.Exogenous VEGF-B also reduced the expression of phospholipase C gamma 1(PLCγ1),phosphatidylinositol 3-kinase(PI3 K),serine/threonine kinase(AKT),and other proteins in the insulin secretion pathway.Upon knockdown of VEGF-B,MIN6 cells exhibited increased insulin secretion and Ca2+ and cAMP levels and upregulated expression of PLCγ1,PI3 K,AKT,and other proteins.CONCLUSION VEGF-B can regulate insulin secretion by modulating the levels of Ca2+ and cAMP.VEGF-B involvement in insulin secretion is related to the expression of PLCγ1,PI3 K,AKT,and other signaling proteins.These results provide theoretical support and an experimental basis for the study of VEGF-B in the pathogenesis of T2 D.

A paradox:Insulin inhibits expression and secretion of resistin which induces insulin resistance

AIM: To confirm whether insulin regulates resistinexpression and secretion during differentiation of 3T3-L1preadipocytes and the relationship of resistin with insulinresistance both in vivo and in vitro.METHODS: Supernatant resistin was measured duringdifferentiation of 3T3-L1 preadipocytes. L6 rat myoblastsand hepatoma cell line H4IIE were used to confirm thecellular function of resistin. Diet-induced obese ratswere used as an insulin resistance model to study therelationship of resistin with insulin resistance.RESULTS: Resistin expression and secretion wereenhanced during differentiation 3T3-L1 preadipocytes.This cellular differentiation stimulated resistin expressionand secretion, but was suppressed by insulin. Resistinalso induced insulin resistance in H4IIE hepatocytes andL6 myoblasts. In diet-induced obese rats, serum resistinlevels were negatively correlated with insulin sensitivity,but not with serum insulin.CONCLUSION: Insulin can inhibit resistin expressionand secretion in vitro, but insulin is not a major regulatorof resistin in vivo . Fat tissue mass affects insulinsensitivity by altering the expression and secretion ofresistin.

Insulin Sensitivity and Insulin Secretion Estimated by Homeostatic Model Assessment (HOMA) in Gestational Diabetes Mellitus

Background: Progressive insulin resistance (IR) is an important pathophysiologic mechanism of gestational diabetes mellitus (GDM). Homeostatic model assessment (HOMA) is commonly used as a parameter of the severity of insulin resistance. Aims: To determine indices of insulin resistance (IR) and β-cell function in gestational diabetes mellitus (GDM). Methods: This cross sectional study was conducted from March 2017 to September 2018 at Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. The study was performed with 41 GDM and equal number of pregnant women with normal glucose tolerance (NGT) diagnosed on basis of WHO criterion-2013 during 24 - 40 weeks of gestation. Serum glucose was measured by glucose oxidase method and fasting serum insulin was measured by chemiluminescent immunoassay. Equations of homeostatic model assessment (HOMA) were used to calculate insulin indices like-insulin resistance (HOMA-IR), β-cell function (HOMA-B) and insulin sensitivity (HOMA-%S). Data were analyzed and compared by statistical tests. Results: A total of eighty-two (82) subjects [41 women with GDM (age: 28.29 ± 3.79 years, BMI: 27.16 ± 4.13 kg/m2) and 41 women with NGT (age: 26.22 ± 5.13 years, BMI: 25.27 ± 3.01 kg/m2)] were included in this study. It was observed that GDM women were significantly older (p = 0.041) and had significantly higher BMI (p = 0.020) than pregnant women with NGT. The GDM group had significantly higher IR as indicated by higher fasting insulin value [GDM vs. NGT;10.19 (7.71 - 13.34) vs. 6.88 (5.88 - 8.47) μIU/ml, median (IQR);p = 0.001] and HOMA-IR [GDM vs. NGT;2.31 (1.73 - 3.15) vs. 1.42 (1.15 - 1.76), median (IQR);p < 0.001], poor β-cell secretory capacity [GDM vs. NGT;HOMA-B: 112.63 (83.52 - 143.93) vs. 128.60 (108.77 - 157.58), median (IQR);p = 0.04] and low insulin sensitivity [GDM vs. NGT;HOMA-%S: 43.29 (31.77 - 57.98) vs. 70.42 (56.86 - 86.59), median (IQR);p < 0.001]. Conclusions: GDM is associated with both insulin resistance and inadequate insulin secretion.

A Novel Insulinotropic Peptide from the Skin Secretions of Amolops loloensis Frog

Various kinds of biologically active peptides have previously been isolated from the skin secretions of Amolops loloensis frog,such as antimicrobial peptides,bradykinin-like peptides and algesic peptides.A novel insulinotropic peptide named amolopin was identified in A.loloensis frog’s skin secretion.Its primary structure sequence was determined by Edman degradation as:FLPIVGKSLSGLSGKL-NH2.BLAST search indicates that the amino acid sequence of amolopin is quite different from other known insulin secretagogues,including mastoparan,exendins and a-latrotoxin,nor does it like incretins(e.g.glucagons like peptide-1 and glucose-dependent insulinotropic ploypeptide)either.However,amolopin shows certain structural similarity with amphibian antimicrobial temporins and vespid chemotactic peptides isolated from Vespa magnifica.Amolopin can stimulate insulin release in INS-1 cells in a dose-dependent manner.Primary investigation on its action mechanisms reveals that amolopin does not increase the influx of Ca2?.In conclusion,a novel 16-amino acid peptide with insulin-releasing activity is initially discovered from the skin secretion of A.loloensis frog.Further work is necessary to evaluate its potential as novel anti-diabetic candidate.

Association of TCF7L2 and GCG Gene Variants with Insulin Secretion,Insulin Resistance,and Obesity in New-onset Diabetes

This cohort study was designed to evaluate the association of transcription factor 7-like 2 （TCF7L2） and proglucagon gene （GCG） variants with disordered glucose metabolism and the incidence of type 2 diabetes mellitus （T2DM） in a rural adult Chinese population. A total of 7,751 non-T2DM participants 〉18 years old genotyped at baseline were recruited. The same questionnaire interview and physical and blood biochemical examinations were performed at both baseline and follow-up. During a median 6 years of follow-up, T2DM developed in 227 participants. After adjustment for potential contributory factors, nominally significant associations were seen between 3T genotype and the recessive model of TCFTI.2 rs7903146 and increased risk of T2DM [hazard ratio （HR）=4.068, 95% confidence interval （CI）： 1.270-13.026; HR=4.051, 95% CI： 1.268-12.946, respectively]. The TT genotype of rs7903146 was also significantly associated with higher fasting plasma insulin level and the homeostasis model assessment of insulin resistance in case of new-onset diabetes. In addition, the TCF7L2 rs290487 TT genotype was associated with abdominal obesity and the GCG rs12104705 CC genotype was associated with both general obesity and abdominal obesity in case of new-onset diabetes.

Efficacy of tolvaptan in an infant with syndrome of inappropriate antidiuretic hormone secretion associated with holoprosencephaly:A case report

BACKGROUND Holoprosencephaly(HPE)is a congenital malformation with various degrees of incomplete separation of the cerebral hemispheres due to differentiation disorders of the forebrain.Although HPE with diabetes insipidus due to associated pituitary dysfunction has been reported,HPE with the syndrome of inappropriate antidiuretic hormone secretion(SIADH)is very rare.Tolvaptan,a vasopressin V2 receptor antagonist,is effective in adults with SIADH.However,there is no report of its efficacy in infants with SIADH.The purpose of this report is to demonstrate that tolvaptan is effective for SIADH in infants and that administration of tolvaptan eliminates the need for restriction of water intake and sodium administration.CASE SUMMARY A 2414-g female infant was born at 38 wk by normal vaginal delivery.Facial anomalies and head magnetic resonance imaging indicated semilobar HPE.After birth,she had hyponatremia due to SIADH and was treated using water and sodium restriction.However,she developed an exaggerated response to the fluid restrictions,resulting in large fluctuations in serum sodium levels.Subsequent administration of tolvaptan improved the fluctuations in serum sodium levels without the need for adjustment of water or sodium administration.Serum sodium was maintained within the normal range after discontinuation of tolvaptan at 80 d of life.There were no side effects,such as hypernatremia or liver dysfunction,during the administration of tolvaptan.CONCLUSION This is the first report on the safety and efficacy of tolvaptan in an infant with SIADH associated with HPE.