EFFECTS OF LONG-TERM GLICLAZIDE TREATMENT ON PANCREATIC HORMONE-RELEASE AND ENTEROPANCREATIC HORMONE CONTENT IN NORMAL RATS

We assessed the effects of two months gliclazide administration in nor mal rats on pancreatic alpha- and beta-cell response to a glucose stim ulus (11.1 mM) using the standard model of the isolated perfused pancr eas. We also determined fasting plasma glucose and pancreatic hormone levels as well as pancreatic and gut hormone tissue concentrations. Tw enty-four rats received therapeutic dosages (2.5 mg/kg/daily) gliclazi de and 24 received a high, largely supra-therapeutic dosage (15 mg/kg/ daily), Twelve rats in each group received one week's post-treatment w ith placebo, A control group of 12 rats received only placebo througho ut the study, In the perfused pancreata of rats on 2.5 mg/kg/daily gli clazide insulin secretory response to a glycaemic stimulus was not sig nificantly reduced. In animals on 15 mg/kg/daily gliclazide the insuli n secretory response to the glycaemic stimulus was significantly reduc ed in both the first and second phases of insulin release (p<0.01 and p<0.002, respectively), Post-treatment with placebo completely reverse d gliclazide's inhibition of the beta-cell function, No changes were o bserved in pancreatic release of glucagon, Although basal glucose and fasting pancreatic hormone levels were not modified by gliclazide at e ither dosage, pancreatic insulin and glucagon tissue contents were red uced in the rats treated with the 2.5 mg/kg/daily (p<0.05 for both); t he reductions were more marked in the group treated with 15 mg/kg/dail y (p<0.005 and p<0.01, respectively). The drop in somatostatin never r eached statistical significance, All reductions in pancreatic hormone content were fully reversed by placebo treatment, The 2.5 mg/kg/daily gliclazide dosage reduced gut hormone content of glucagon (p<0.025), s omatostatin (p<0.025) and vasoactive intestinal peptide (VIP) (p<0.05) and reductions were more marked after administration at high doses. N o effect was observed on gut content of gastric inhibitory peptide (GI P) after either dosage of gliclazide, Placebo administration completel y reversed all effects of gliclazide, Diab. Nutr. Metab. 11: 104-113, 1998. (C) 1998, Editrice Kurtis.