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ZB-16, a Novel GPR119 Agonist, Relieves the Severity of Streptozotocin-Nicotinamide-Induced Diabetes in Rats.

ABSTRACT: GPR119 is involved in the regulation of incretin and insulin secretion, so the GPR119 agonists have been suggested as novel antidiabetic medications. The purpose of this work was to assess the influence of novel GPR119 agonist ZB-16 on the glucose utilization, insulin, and glucagon-like peptide-1 (GLP-1) secretion and the morphology of pancreas in rats with streptozotocin-nicotinamide-induced diabetes. 45 male Wistar rats were used in the study. The criteria of streptozotocin-nicotinamide-induced diabetes were blood glucose levels of 9-14?mmol/l measured in fasting conditions on the third day since administration of streptozotocin (65?mg/kg) and nicotinamide (230?mg/kg). Animals failed to reach the criteria were excluded from the experiment. The substances were administered per os once per day for 28?days. Measurements included blood glucose monitoring (every 7?days), glucose tolerance test (every 14?days), the assessment of insulin and GLP-1 levels in blood plasma (28?days after beginning), and the results of immunohistochemical staining of pancreas. It was found that ZB-16 (1?mg/kg per os, once a day) decreases the blood glucose levels under fasting conditions and improves the glucose utilization. These changes were associated with the increase in stimulated secretion of GLP-1 and insulin, accompanied by the growth of insulin-positive cells in pancreas. Thus, ZB-16 could be a promising antidiabetic drug for oral administration.

SUBMITTER: Tyurenkov IN

PROVIDER: S-EPMC5500613 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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ZB-16, a Novel GPR119 Agonist, Relieves the Severity of Streptozotocin-Nicotinamide-Induced Diabetes in Rats.

Tyurenkov Ivan N IN Kurkin Denis V DV Bakulin Dmitry A DA Volotova Elena V EV Chafeev Mikhail A MA Smirnov Alexey V AV Smirnov Alexey V AV Morkovin Evgeny I EI

Frontiers in endocrinology 20170707

GPR119 is involved in the regulation of incretin and insulin secretion, so the GPR119 agonists have been suggested as novel antidiabetic medications. The purpose of this work was to assess the influence of novel GPR119 agonist ZB-16 on the glucose utilization, insulin, and glucagon-like peptide-1 (GLP-1) secretion and the morphology of pancreas in rats with streptozotocin-nicotinamide-induced diabetes. 45 male Wistar rats were used in the study. The criteria of streptozotocin-nicotinamide-induce ...[more]

PMID: 28736546

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Project description:BackgroundPolysaccharides decrease the glucose level by inhibiting α-glucosidase enzyme which further increases the level of GLP-1 (Glucagon-like peptide 1) to increase the insulin level as per earlier reports.ObjectiveSimilar hypothesis was designed in present study to investigate the α-glucosidase enzyme inhibition and involvement of GLP-1 in antidiabetic mechanism of Acacia tortilis polysaccharides (AEATP) in diabetic rats. Isolated polysaccharides were analyzed for their chemical nature by using HPLC and FTIR method.Materials and methodsMale albino wistar rats were divided into control, diabetic, diabetic + voglibose, diabetic + glimepiride, diabetic+250, 500, 1000 mg/kg of AEATP, diabetic + glimepiride + voglibose, diabetic + glimepiride+ 250, 500 and 1000 mg/kg AEATP, diabetic + GLP-1 antagonist+250, 500 and 1000 mg/kg AEATP. Plasma glucose, insulin and active GLP-1 levels were measured 15 min after OGTT. Fasting blood glucose, Plasma triglycerides, glycated hemoglobin (HbA1c), Fasting insulin, pancreatic insulin content, ileum and colon GLP-1 content were assessed at 5th week. Association of alpha-glucosidase was also assessed with GLP-1 and insulin.ResultsAEATP significantly attenuated hyperglycemia by increasing insulin level in plasma and pancreas and increased active GLP-1 as well as insulin level in diabetic rats after OGTT. GLP-1 content was significantly increased in ileum and colon by inhibiting alpha-glucosidase. Involvement of GLP-1 in antihyperglycemic effect of AEATP was confirmed by using GLP-1 antagonist. Moreover, AEATP significantly improved dyslipidemia in diabetic rats. HPLC analysis of A. tortilis polysaccharide comprised four specific monosaccharides (Rhamnose, Glucuronic acid, glucose and galactose) and FTIR spectrum shown band at 3430.6 cm-1 (O-H stretching), 2940.3 cm-1 (C-H linkage), 1630.4 cm-1 (carbonyl stretching), 1410 cm-1 (uronic acid) and 1030.5 cm-1 (glycosidic linkage).ConclusionIt can be concluded that antidiabetic effect of AEATP is through the modulation of GLP-1 level in plasma and intestinal tissue via alpha glucosidase inhibition.

Project description:IntroductionIncrease in the prevalence of type-2 diabetes in Sub-Sahara Africa has created the need for robust treatment and management programs. However, an effective diabetes management program requires a high annual budget that most countries in this region cannot afford. That said, various plants and plant products in this region have either been confirmed and/or ethnopharmacologically used for the management of type-2 diabetes.AimTo investigate the antidiabetic and insulin secretory effects of an alkaloidal extract derived from Zanthoxylum zanthoxyloides in normoglycemic and experimental diabetic rats.Materials and methodsAlkaloidal extract was prepared from leaves of Z anthoxylum zanthoxyloides (ZZAE). Nicotinamide/streptozotocin-induced type-2 diabetes was modeled in male Sprague Dawley rats weighing between 130 to 150 g. The experimental diabetic rats were grouped into six treatment groups [Model, 20% Tween20, chlorpropamide, and ZZAE (50, 100, and 150 mg/kg)], and one control group. Fasting blood glucose (FBG), and body weight were measured weekly. Rats were sacrificed 2 days after treatment under chloroform anesthesia to collect blood samples and to isolate major organs for biochemical, and histological analyses respectively. Islets of Langerhans were isolated from normoglycemic rats and co-cultured with ZZAE and chlorpropamide (10 μg/mL) to assess the insulin secretory effect of ZZAE.ResultsZZAE improved glucose kinetics curve in normoglycemic (p < 0.001) and experimental diabetic rats (p < 0.05) compared to the model. ZZAE (100 and 150 mg/kg) restored islets population, and improved kidney, and liver, histoarchitecture. ZZAE (150 mg/kg) improved post-treatment serum insulin levels compared to the model group (p < 0.001) and the Chlorpropamide group (p < 0.05). ZZAE also restored glycogen synthesis in skeletal muscles of experimental diabetic rats and stimulated insulin secretion in pancreatic islets of Langerhans isolated from normoglycemic rats.ConclusionThese results showed that ZZAE has active alkaloids that can be explored for diabetes management.

Dataset Information

ZB-16, a Novel GPR119 Agonist, Relieves the Severity of Streptozotocin-Nicotinamide-Induced Diabetes in Rats.

Publications

ZB-16, a Novel GPR119 Agonist, Relieves the Severity of Streptozotocin-Nicotinamide-Induced Diabetes in Rats.

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