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

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 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 , 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.