scholarly journals Light at night acutely impairs glucose tolerance in a time-, intensity- and wavelength-dependent manner in rats

Diabetologia ◽  
2017 ◽  
Vol 60 (7) ◽  
pp. 1333-1343 ◽  
Author(s):  
Anne-Loes Opperhuizen ◽  
Dirk J. Stenvers ◽  
Remi D. Jansen ◽  
Ewout Foppen ◽  
Eric Fliers ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Dependent Manner ◽  
Light At Night

scholarly journals 4-Hydroxyisoleucine: experimental evidence of its insulinotropic and antidiabetic properties

1999 ◽  
Vol 277 (4) ◽  
pp. E617-E623 ◽  
Author(s):  
Christophe Broca ◽  
René Gross ◽  
Pierre Petit ◽  
Yves Sauvaire ◽  
Michèle Manteghetti ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Insulin Response ◽  
Oral Glucose ◽  
Dependent Manner ◽  
Insulin Dependent ◽  
Glucose Tolerance Tests ◽  
Insulin Dependent Diabetic ◽  
Single Intravenous Administration

We have recently shown in vitro that 4-hydroxyisoleucine (4-OH-Ile), an amino acid extracted from fenugreek seeds, potentiates insulin secretion in a glucose-dependent manner. The present study was designed to investigate whether 4-OH-Ile could exert in vivo insulinotropic and antidiabetic properties. For this purpose, intravenous or oral glucose tolerance tests (IVGTTs and OGTTs, respectively) were performed not only in normal animals but also in a type II diabetes rat model. During IVGTT in normal rats or OGTT in normal dogs, 4-OH-Ile (18 mg/kg) improved glucose tolerance. The lactonic form of 4-OH-Ile was ineffective in normal rats. In non-insulin-dependent diabetic (NIDD) rats, a single intravenous administration of 4-OH-Ile (50 mg/kg) partially restored glucose-induced insulin response without affecting glucose tolerance; a 6-day subchronic administration of 4-OH-Ile (50 mg/kg, daily) reduced basal hyperglycemia, decreased basal insulinemia, and slightly, but significantly, improved glucose tolerance. In vitro, 4-OH-Ile (200 μM) potentiated glucose (16.7 mM)-induced insulin release from NIDD rat-isolated islets. So, the antidiabetic effects of 4-OH-Ile on NIDD rats result, at least in part, from a direct pancreatic B cell stimulation.

scholarly journals Tamoxifen Improves Glucose Tolerance in a Delivery-, Sex-, and Strain-Dependent Manner in Mice

Endocrinology ◽  
2019 ◽  
Vol 160 (4) ◽  
pp. 782-790 ◽  
Author(s):  
Alexis M Ceasrine ◽  
Nelmari Ruiz-Otero ◽  
Eugene E Lin ◽  
David N Lumelsky ◽  
Erica D Boehm ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Dependent Manner ◽  
Strain Dependent

scholarly journals GPR119 Regulates Murine Glucose Homeostasis Through Incretin Receptor-Dependent and Independent Mechanisms

Endocrinology ◽  
2010 ◽  
Vol 152 (2) ◽  
pp. 374-383 ◽  
Author(s):  
Grace Flock ◽  
Dianne Holland ◽  
Yutaka Seino ◽  
Daniel J. Drucker
Keyword(s):  
Insulin Secretion ◽  
Gastric Emptying ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Peptide Yy ◽  
Cell Receptor ◽  
Dependent Manner ◽  
Glucagon Like Peptide 1

Abstract G protein-coupled receptor 119 (GPR119) was originally identified as a β-cell receptor. However, GPR119 activation also promotes incretin secretion and enhances peptide YY action. We examined whether GPR119-dependent control of glucose homeostasis requires preservation of peptidergic pathways in vivo. Insulin secretion was assessed directly in islets, and glucoregulation was examined in wild-type (WT), single incretin receptor (IR) and dual IR knockout (DIRKO) mice. Experimental endpoints included plasma glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide YY. Gastric emptying was assessed in WT, Glp1r−/−, DIRKO, Glp2r−/−, and GPR119−/− mice treated with the GPR119 agonist AR231453. AR231453 stimulated insulin secretion from WT and DIRKO islets in a glucose-dependent manner, improved glucose homeostasis, and augmented plasma levels of GLP-1, GIP, and insulin in WT and Gipr−/−mice. In contrast, although AR231453 increased levels of GLP-1, GIP, and insulin, it failed to lower glucose in Glp1r−/− and DIRKO mice. Furthermore, AR231453 did not improve ip glucose tolerance and had no effect on insulin action in WT and DIRKO mice. Acute GPR119 activation with AR231453 inhibited gastric emptying in Glp1r−/−, DIRKO, Glp2r−/−, and in WT mice independent of the Y2 receptor (Y2R); however, AR231453 did not control gastric emptying in GPR119−/− mice. Our findings demonstrate that GPR119 activation directly stimulates insulin secretion from islets in vitro, yet requires intact IR signaling and enteral glucose exposure for optimal control of glucose tolerance in vivo. In contrast, AR231453 inhibits gastric emptying independent of incretin, Y2R, or Glp2 receptors through GPR119-dependent pathways. Hence, GPR119 engages multiple complementary pathways for control of glucose homeostasis.

β-Glycosphingolipids improve glucose intolerance and hepatic steatosis of the Cohen diabetic rat

2009 ◽  
Vol 296 (1) ◽  
pp. E72-E78 ◽  
Author(s):  
Ehud Zigmond ◽  
Sarah W. Zangen ◽  
Orit Pappo ◽  
Miriam Sklair-Levy ◽  
Gadi Lalazar ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Immune System ◽  
Glucose Tolerance ◽  
Immune Modulation ◽  
Cell Function ◽  
Liver Steatosis ◽  
Diabetic Rat ◽  
Oral Glucose ◽  
Dependent Manner ◽  
Mri Imaging

A link between altered levels of various gangliosides and the development of insulin resistance was described in transgenic mice. Naturally occurring glycosphingolipids were shown to exert immunomodulatory effects in a natural killer T (NKT) cell-dependent manner. This study examined whether glycosphingolipid-induced modulation of the immune system may reduce pancreatic and liver steatosis and stimulate insulin secretion in the Cohen diabetes-sensitive (CDS) rat, a lean model of non-insulin-resistant, nutritionally induced diabetes. Four groups of CDS rats fed a diabetogenic diet were treated with daily intraperitoneal injections of glycosphingolipids β-glucosylceramide, β-lactosylceramide, a combination of both (IGL), or vehicle (PBS) for up to 45 days. Immune modulation was assessed by fluorescence-activated cell sorting analysis of intrahepatic and intrasplenic lymphocytes. Steatosis was assessed by MRI imaging and histological examination of liver and pancreas, Blood glucose and plasma insulin concentrations were assessed during an oral glucose tolerance test. Administration of glycosphingolipids, particularly IGL, increased intrahepatic trapping of CD8 T and NKT lymphocytes. Pancreatic and liver histology were markedly improved and steatosis was reduced in all treated groups compared with vehicle-treated rats. Insulin secretion was restored after glycosphingolipid treatment, resulting in improved glucose tolerance. The immunomodulatory effect of β-glycosphingolipids improved the β-cell function of the hyperglycemic CDS rat. Thus our results suggest a role for the immune system in the pathogenesis of diabetes in this model.

scholarly journals Meteorin-like (Metrnl) adipomyokine improves glucose tolerance in type 2 diabetes via AMPK pathway

2018 ◽  
Author(s):  
Jung Ok Lee ◽  
Hye Jeong Lee ◽  
Yong Woo Lee ◽  
Jeong Ah Han ◽  
Min Ju Kang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Underlying Mechanism ◽  
Dependent Manner ◽  
Beneficial Effects ◽  
Ampk Pathway

AbstractMeteorin-like (metrnl) is a recently identified adipomyokine that has beneficial effects on glucose metabolism. However, its underlying mechanism of action is not completely understood. In this study, we have shown that a level of metrnl increase in vitro under electrical-pulse-stimulation (EPS) and in vivo in exercise mice, suggesting that metrnl is an exercise-induced myokine. In addition, metrnl increases glucose uptake through the calcium-dependent AMPK pathway. Metrnl also increases the phosphorylation of HDAC5, a transcriptional repressor of GLUT4, in an AMPK-dependent manner. Phosphorylated HDAC5 interacts with 14-3-3 proteins and sequesters them in the cytoplasm, resulting in the activation of GLUT4 transcription. The intraperitoneal injection of recombinant metrnl improves glucose tolerance in mice with high fat-induced obesity or type 2 diabetes (db/db), but this is not seen in AMPK β1β2 muscle-specific null mice (AMPK β1β2 MKO). In conclusion, we have demonstrated that metrnl induces beneficial effects on glucose metabolism via AMPK and is a promising therapeutic candidate for glucose-related diseases such as type 2 diabetes.

scholarly journals Antidiabetic potentials of Syzygium guineense methanol leaf extract

2016 ◽  
Vol 5 (4) ◽  
pp. 150-156
Author(s):  
Ifeoma Chinwude Ezenyi ◽  
◽  
Oluchi Nneka Mbamalu ◽  
Lucy Balogun ◽  
Liberty Omorogbe ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Leaf Extract ◽  
Density Lipoprotein ◽  
Hepatic Glycogen ◽  
Oral Glucose ◽  
Dependent Manner ◽  
Oral Glucose Tolerance ◽  
Control Serum ◽  
Syzygium Guineense ◽  
Alpha Glucosidase

This study examines the effects of a methanol extract of Syzygium guineense leaves in streptozotocin (STZ) - induced diabetes, evaluates its effect on alpha glucosidase and 2, 2-diphenyl-1-picrylhydrazyl radical. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (60 mg/kg). An oral glucose tolerance test was performed after diabetes induction and repeated after 14 days of treatment with the extract. The extract elicited antihyperglycemic action in diabetic rats evidenced by an improved oral glucose tolerance. A dose of 250 mg/kg of extract significantly (P<0.01, 0.001) enhanced glucose clearance at the end of treatment period and was comparable with metformin, the group also showed increase in hepatic glycogen content by 33.9% relative to the diabetic control. Serum biochemical analysis showed that the extract improved indices of renal and hepatic function by reduction in serum albumin, creatinine, liver enzymes, total and direct bilirubin. Similarly, the extract reduced serum cholesterol, triglycerides and high density lipoprotein (HDL) in a non-dose dependent manner; treatment with 250 mg/kg extract caused significant (P<0.05) reduction of HDL. Groups which received 250 and 500 mg/kg of extract showed reversal of glomerular damage compared with the diabetic untreated group. The extract also exhibited concentration-dependent antioxidant activity (EC50= 0.2 mg/ml) and statistically significant (P<0.01, 0.001) alpha glucosidase inhibitory effect (IC50= 6.15 mg/ml). These findings show the antidiabetic potential of S. guineense leaf extract, likely mediated through its ability to inhibit alpha glucosidase, scavenge free radicals and increase intrahepatic glucose uptake and storage.

scholarly journals Partial Blockade of Kv2.1 Channel Potentiates GLP-1's Insulinotropic Effects in Islets and Reduces Its Dose Required for Improving Glucose Tolerance in Type 2 Diabetic Male Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (1) ◽  
pp. 114-123 ◽  
Author(s):  
Rauza Sukma Rita ◽  
Katsuya Dezaki ◽  
Tomoyuki Kurashina ◽  
Masafumi Kakei ◽  
Toshihiko Yada
Keyword(s):  
Protein Kinase ◽  
Adverse Effects ◽  
Glucose Tolerance ◽  
Protein Kinase A ◽  
Insulin Release ◽  
Dependent Manner ◽  
Β Cells ◽  
Type 2 Diabetic ◽  
Kinase A

Abstract Glucagon-like peptide-1 (GLP-1)-based medicines have recently been widely used to treat type 2 diabetic patients, whereas adverse effects of nausea and vomiting have been documented. Inhibition of voltage-gated K+ channel subtype Kv2.1 in pancreatic β-cells has been suggested to contribute to mild depolarization and promotion of insulin release. This study aimed to determine whether the blockade of Kv2.1 channels potentiates the insulinotropic effect of GLP-1 agonists. Kv2.1 channel blocker guangxitoxin-1E (GxTx) and GLP-1 agonist exendin-4 at subthreshold concentrations, when combined, markedly increased the insulin release and cytosolic Ca2+ concentration ([Ca2+]i) in a glucose-dependent manner in mouse islets and β-cells. Exendin-4 at subthreshold concentration alone increased islet insulin release and β-cell [Ca2+]i in Kv2.1+/− mice. The [Ca2+]i response to subthreshold exendin-4 and GxTx in combination was attenuated by pretreatment with protein kinase A inhibitor H-89, indicating the protein kinase A dependency of the cooperative effect. Furthermore, subthreshold doses of GxTx and GLP-1 agonist liraglutide in combination markedly increased plasma insulin and improved glucose tolerance in diabetic db/db mice and NSY mice. These results demonstrate that a modest suppression of Kv2.1 channels dramatically raises insulinotropic potency of GLP-1-based drugs, which opens a new avenue to reduce their doses and associated adverse effects while achieving the same glycemic control in type 2 diabetes.

scholarly journals Evaluation of a Standardized Extract fromMorus albaagainstα-Glucosidase Inhibitory Effect and Postprandial Antihyperglycemic in Patients with Impaired Glucose Tolerance: A Randomized Double-Blind Clinical Trial

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Seung Hwan Hwang ◽  
Hong Mei Li ◽  
Soon Sung Lim ◽  
Zhiqiang Wang ◽  
Jae-Seung Hong ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Clinical Signs ◽  
Inhibitory Effect ◽  
Postprandial Hyperglycemia ◽  
Dependent Manner ◽  
Double Blind ◽  
Double Blind Clinical Trial

To evaluate the antihyperglycemic effect of a standardized extract of the leaves ofMorus alba(SEMA), the present study was designed to investigate theα-glucosidase inhibitory effect and acute single oral toxicity as well as evaluate blood glucose reduction in animals and in patients with impaired glucose tolerance in a randomized double-blind clinical trial. SEMA was found to inhibitα-glucosidase at a fourfold higher level than the positive control (acarbose), in a concentration-dependent manner. Moreover, blood glucose concentration was suppressed by SEMAin vivo. Clinical signs and weight changes were observed when conducting an evaluation of the acute toxicity of SEMA through a single-time administration, with clinical observation conducted more than once each day. After administration of the SEMA, observation was for 14 days; all of the animals did not die and did not show any abnormal symptoms. In addition, the inhibitory effects of rice coated with SEMA were evaluated in a group of impaired glucose tolerance patients on postprandial glucose and a group of normal persons, and results showed that SEMA had a clear inhibitory effect on postprandial hyperglycemia in both groups. Overall, SEMA showed excellent potential in the present study as a material for improving postprandial hyperglycemia.

scholarly journals Dietary supplementation of inulin alleviates metabolism disorders in gestational diabetes mellitus mice via RENT/AKT/IRS/GLUT4 pathway

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Miao Miao ◽  
Yongmei Dai ◽  
Can Rui ◽  
Yuru Fan ◽  
Xinyan Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Gestational Diabetes ◽  
Glucose Tolerance ◽  
Gestational Diabetes Mellitus ◽  
Glucose Homeostasis ◽  
Molecular Mechanisms ◽  
Fasting Blood Glucose ◽  
High Dose ◽  
Dependent Manner

Abstract Background Gestational diabetes mellitus (GDM) has significant short and long-term health consequences for both the mother and child. There is limited but suggestive evidence that inulin could improve glucose tolerance during pregnancy. This study assessed the effect of inulin on glucose homeostasis and elucidated the molecular mechanisms underlying the inulin-induced antidiabetic effects during pregnancy. Method Female C57BL/6 mice were randomized to receive either no treatment, high-dose inulin and low-dose inulin for 7 weeks with measurement of biochemical profiles. A real-time2 (RT2) profiler polymerase chain reaction (PCR) array involved in glycolipid metabolism was measured. Results Inulin treatment facilitated glucose homeostasis in a dose-dependent manner by decreasing fasting blood glucose, advanced glycation end products and total cholesterol, and improving glucose tolerance. Suppressing resistin (RETN) expression was observed in the inulin treatment group and the expression was significantly correlated with fasting blood glucose levels. The ratios of p-IRS to IRS and p-Akt to Akt in liver tissue and the ratio of p-Akt to Akt in adipose tissue as well as the expression level of GLUT4 increased significantly after inulin treatment. Conclusions Our findings indicated improvement of glucose and lipid metabolism by inulin was to activate glucose transport through the translocation of GLUT4 which was mediated by insulin signaling pathway repairment due to decreased expression of RETN and enhanced phosphorylation of IRS and Akt in GDM mice.

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