Cholecystokinin octapeptide: a potential growth factor for pancreatic beta cells in diabetic rats.

CONTEXT 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. OBJECTIVE We investigated the possible role of CCK-octapeptide (CCK-8) in generating islet cell proliferation in type 1 and type 2 diabetic rats. METHODS 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. MAIN OUTCOME MEASURES 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. RESULTS 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. CONCLUSIONS 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.