Paper Title
CROCIN STIMULATES INSULIN SECRETION VIA THE ACTIVATION OF K+ AND Ca2+CHANNELS IN PERFUSED RAT PANCREAS AND BRIN-BD11 CELLS AND INHIBITS CARBOHYDRATE DIGESTION AND ABSORPTION IN DIABETIC MODEL RATS

Abstract
The hypoglycemic effects of crocin isolated from Crocus sativus L. have previously been reported in rats and humans. In the present study, the effects of crocin on insulin secretion together with the exploration of its mechanism underlying insulin action were evaluated. To further study, the inhibitory effects of carbohydrate digestion and absorption, DPP-4in diabetic Long-evans rats was assayed.Insulin secretory effects of crocin were evaluated perfused rat pancreas and BRIN-BD11 cells. For the studies on the mechanism underlying the insulin secretory activity, 11 mM glucose,50µM verapamil, 8mM diazoxide, and 200 µM IBMX were used. Sucrose malabsorption was tested in six different segments of the gastrointestinal (GI) tract of the rats following oral sucrose load. To study the effect of crocin on glucose absorption, an in situ intestinal perfusion (from duodenum to 40 cm) was performed. The effect on GI tract motility was assayed using the BaSO4 milk travel test.Crocin produced a 5-fold increase in insulin secretion from perfused pancreas (p<0.01). Perfusion of the pancreas with Crocin and 11 mM glucose caused a significant (P<0.01) steep rise in insulin release. The infusion of diazoxide (8 mM), a KATP channel opener, and Verapamil (50 µM), a voltage-dependent Ca2+ channel blocker in the presence of 11 mM glucose significantly inhibited insulin secretion by Crocin which indicates that the effect was associated with glucose metabolism, Ca2+ signals, and KATP channel activity. The insulin secretion in the presence of a cAMP competitor (IBMX, 200 µM) was not enhanced suggesting that the insulin secretory action of Crocin was not related to the second messenger systems, such as adenylate cyclase-cAMP or phosphatidylinositol pathway, or on exocytosis.Crocin inhibited glucose absorption and increased the remaining sucrose content in the gut after oral sucrose load. It also decreased glucose during in situ intestinal perfusion with glucose and promoted gut motility.In conclusion, crocin could be a potential antidiabetic agent in diabetes therapy. Keywords - Crocin, Diabetes, Insulin secretion, Pancreatic perfusion, Gut perfusion, Sucrose malabsorption.