sincalide and Diabetes-Mellitus--Type-1

Diabetes is associated with the reduction of beta cell mass and activity. Cholecystokinin (CCK) is known to induce growth of the exocrine pancreas and to stimulate insulin secretion.. We investigated the possible role of CCK-octapeptide (CCK-8) in generating islet cell proliferation in type 1 and type 2 diabetic rats.. Streptozotocin-induced type 1 diabetic rats, streptozotocin/nicotinamide-induced type 2 diabetic rats and non-diabetic rats were subjected to CCK-8 (1, 2 and 4 microg/kg) or saline injections (for the control group), three times daily for 8 successive days.. The islets of Langerhans were analyzed morphometrically; the beta-cell function was evaluated by an oral glucose tolerance test, and plasma basal glucose and insulin concentrations.. In type 1 diabetic rats, CCK-8 induced an increase in beta cell surface associated with a marked increase in the mitotic index; this effect appeared at a concentration of 1 microg/kg CCK-8 and was the highest at a concentration of 4 microg/kg CCK-8. In addition, pancreatic- and plasma-insulin concentrations increased while fasting blood glucose concentrations were reduced when compared to saline-treated rats but the glycemic response to an oral glucose challenge did not significantly improve. In type 2 diabetic rats and in non-diabetic rats, CCK-8 treatment did not significantly affect either the structure or the functional state of beta-cells.. CCK-8 could improve blood glucose concentrations in type 1 diabetic rats correlated with an increase in beta cell mass probably potentiated by the chronic hyperglycemic state.

Topics: Animals; Blood Glucose; Cell Division; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Evaluation, Preclinical; Glucose Tolerance Test; Insulin; Insulin Secretion; Islets of Langerhans; Male; Niacinamide; Rats; Rats, Wistar; Sincalide; Streptozocin

To investigate the role of cholecystokinin (ChCK) in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) and to search the ways of its treatment with good prospects we conducted a comparative study of the effects of chronic conjunctive instillations (c.i.)) and intracerebroventricular administrations (i.c.v.) of cholecystokinin octapeptide (ChCK-8) to intact and streptozotocin-induced IDDM rats. The state of alpha- and beta-cells in pancreatic islets was studied by immunocytochemical method with a subsequent quantitative analysis on an automatic image analysis system. Our investigation has shown that in healthy rats both i.c.v. and c.i. administrations of ChCK-8 induced a significant increase in glycemia due to stimulation of alpha-cells and depression of beta-cells. However effects of ChCK-8 on the synthesis and secretion of insulin prevailed at i.c.v. administrations, while ChCK-8 administrated by c.i. was more potent in stimulating alpha-cells. Both ways of ChCK-8 administrations to a IDDM rats caused a positive effect on those animals by inhibiting a destruction of beta-cells, stimulating their function, and decreasing the content of alpha-cells in pancreatic islets which lead to a significant increase in insulin and a decrease in glucose in blood.

Topics: Animals; Conjunctiva; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Injections, Intraventricular; Instillation, Drug; Insulin; Islets of Langerhans; Male; Rats; Rats, Wistar; Sincalide