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.
Highlights
Incretins are metabolic hormones which decrease the blood glucose level
Based on the previous studies of ZB-16 [7], this stage aims to estimate the hypoglycemic action of the GPR119 receptor agonist in animals with type 2 diabetes mellitus during a 28-day treatment
The new GPR119 agonist ZB-16 demonstrated the mild hypoglycemic activity on glucose-loaded animals with the experimental type 2 diabetes mellitus caused by streptozotocin and nicotinamide administration
Summary
Incretins are metabolic hormones which decrease the blood glucose level This effect is provided by the increase in the amount of insulin released from pancreatic β-cells. They slow down the rate of absorption of nutrients into the blood stream by reducing gastric emptying and may directly reduce food intake. They inhibit glucagon release from the alpha cells of the islets of Langerhans. GLP-1, one of the main candidate molecules, is rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). This requires the continuous subcutaneous infusion, which is not convenient for patients. Drugs acting via the incretin system are DPP-4 inhibitors
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