Antidiabetic Activity of Momordica charantia L. and Mechanism of Insulin Secretion of 1-Butanol Soluble Part on Type 2 Diabetic Model Rats

The in vivo effects of fruit pulp juice (MC-PJ) of Momordica charantia and its 1-butanol soluble part (MC-BP) and aqueous soluble part (MC-AP) on blood glucose of type 2 diabetic rats were studied. In vitro insulin secretion in response to MC-BP and MC-AP from whole perfused pancreas was measured. For elucidating the mechanism of insulinotropic action, the insulin secretory activity of MC-BP in the presence of 11 mM glucose, 50 μM verapamil (Ca++ channel blocker), 8 mM diazoxide (K+ ATP channel opener) and 10 mM theophylline (cAMP phosphodiesterase inhibitor) were studied. Serum glucose was measured by glucose oxidase-peroxidase method and rat insulin was assayed by specific ELISA. In the in vivo study, MC-BP significantly opposed the rise of serum glucose compared to control at 105 min (p<0.05). Although the MC-AP and MC-PJ lowered the serum glucose both at 60 and 105 min, these were not statistically significant. In the in vitro study, only MC-BP produced 22-fold increase in insulin secretion from the perfused pancreas at nonstimulatory glucose level, which was significant (basal vs. MC-BP, 0.071±0.009 vs. 1.563±0.150 ng/ml, p<0.001). The MC-BP also enhanced the insulin secretion from the glucose-stimulated pancreas (p<0.001). The MC-BP induced insulin secretion was not affected in presence of diazoxide and verapamil. The obtained results also showed that MC-BP enhanced the insulin secretory effect of theophylline (p<0.001). The findings indicate that MC-BP has stimulatory effects on physiological pathways of insulin secretion which may underlie its reported antidiabetic action. Dhaka Univ. J. Pharm. Sci. 19(2): 111-117, 2020 (December)

Arginine vasopressin inhibits fluid secretion in guinea pig pancreatic duct cells

The effects of arginine vasopressin (AVP) on pancreatic ductal secretion were studied in guinea pigs. In the isolated vascularly perfused pancreas, AVP reduced secretin-stimulated fluid secretion and increased the vascular resistance when the perfusion rate was held constant. In the isolated interlobular duct segments, AVP inhibited secretin-stimulated fluid secretion, indicating the direct inhibitory action of AVP on the duct cells. AVP affected neither the basal nor the secretin-induced cAMP productions, suggesting that AVP inhibits the fluid secretion at a point distal to the production of cAMP. AVP increased intracellular Ca2+ concentration ([Ca2+]i) in the absence of extracellular Ca2+. When [Ca2+]iwas elevated by the application of thapsigargin, AVP caused a rapid decrease in [Ca2+]i. AVP seems to activate both Ca2+release from intracellular stores and Ca2+ efflux across the plasma membrane, but its relation to the inhibition of fluid secretion remains to be clarified. It is concluded that AVP directly inhibits secretin-stimulated ductal fluid secretion in the guinea pig pancreas.