Leptin is able to stimulate pancreatic enzyme secretion via activation of duodeno-pancreatic reflex and CCK release

Leptin, 16- kDa protein produced and secreted from white adipocytes is known to regulate food intake and energy expenditure. Leptin receptors have been detected in the pancreas and it has been shown that systemic application of this protein diminished postprandial pancreatic secretion. Leptin is also produced in the stomach and released into the gastrointestinal lumen but the implication of luminal Leptin in the regulation of pancreatic Enzyme secretion has not been elucidated. The aim of our study was to evaluate the effects of intraduodenal (i.d.) Leptin administration on pancreatic Enzyme secretion and to assess the involvement of afferent nerves and CCK in above effects. The secretory studies were carried out on anaesthetized Wistar rats with acute pancreatic fistulae. Leptin was administered to the Animals at doses of 0.1 1.0 or 10.0 microg/kg i.d. Tarazepide (2.5 mg/kg i.d.), a CCK(1) receptor antagonist, was given to the rats prior to the application of Leptin. Rats with capsaicin deactivated sensory nerves were used in part of the study. Samples of pancreatic juice were taken at 15 min intervals to measure the volume flow and protein and amylase concentrations. CCK plasma level was measured by radioimmunoassay (RIA) following administration of Leptin to the rats. Intraduodenal administration of Leptin (1.0 or 10.0 microg/kg) to the fasted rats significantly and dose-dependently increased pancreatic protein and amylase outputs. Pancreatic secretory responses to Leptin were totally abolished by prior capsaicin deactivation of sensory nerves or by pretreatment of the rats with tarazepide. Under basal conditions plasma CCK level averaged about 15.46 +/- 1,4 pg/ml. Exogenous Leptin, given i.d. at doses of 0.1 1.0 or 10.0 microg/kg i.d. to the rats with intact or capsaicin-deactivated sensory nerves resulted in dose-dependent rise of plasma CCK level, reaching the highest value at the dose of 10.0 microg/kg i.d. We conclude that Leptin given i.d. stimulates pancreatic Enzyme secretion and this effect could be related to the stimulation of CCK release and activation of duodeno-pancreatic reflexes.