Pancreatic Polypeptide の生理作用に関する研究、とくにインスリン分泌調節機構への関与について
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Pancreatic polypeptide (PP) has a broad spectrum of biological actions on gastrointestinal functions including inhibition of pancreatic exocrinc secretion, relaxation of the gallbladder, and contraction of the choledocal sphincter, in men and dogs. However, in regard to the action of PP on pancreatic endocrine secretion, previous reports are conflicting. The present study was, therefore, undertaken to evaluate the effect of intravenously infused PP on insulin secretion in dogs, and, if any, to determine whether it is mediated by nervous system or not. PP used was highly purified porcine PP (pPP) which is identical in structure to canine PP (cPP). pPP was infused intravenously in healthy conscious dogs at a dose of 1 and 2 μg/kg/hr (n=7) producing plasma PP concentrations of 593.8±49.2 pg/ml (mean±S. E. M) and 996.4±102.6 pg/ml, respectively. These levels are similar to and two fold higher than those after a mixed meal in healthy mongrel dogs respectively. Preliminary studies revealed that intravenous infusion of pPP at 1 or 2 μg/kg/hr did not significantly change basal insulin and blood glucose levels over a one-hour period. As stimuli of insulin secretion, modified sham feeding (MSF: sight and smell of a test meal for 5 min.), glucose infusion (0.5 g/kg, intravenously), highly purified porcine secretin infusion (1.5U/kg/5 min, intravenously), and synthetic CCK-octapeptide infusion (0.07 μg/kg/5 min, intravenously) were applied 60 minutes after the start of pPP (1 or 2 pg/kg/hr) or saline infusion on each of three different days. MSF led to a rapid and significant increase in plasma insulin concentration from a basal level of 4.8 ± 0.9 to a peak level of 20.6±3.4 μU/ml at 2.5 min. However, intravenous infusions of pPP (1 and 2 μg/kg/hr.) markedly reduced the peak value of insulin secretion induced by MSF, and suppressed integrated insulin response to MSF by about -15% and 7% at the low and high doses of pPP, respectively. Moreover, these two doses intravenously infused pPP displayed a moderate inhibitory effect on glucose-stimulated insulin release by about 58% and 76%, respectively, whereas it had no effect on insulin secretion induced by secretin and CCK-8. AS a due to elucidate the mechanism of the suppressive action of PP on insulin secretion, the similar tests were performed before and after vagotomy in the same dogs. Four dogs underwent transthoratic bilateral truncal vagotomy with pyloroplasty. Vagotomy has abolished MSF-stimulated insulin release, but not affected on insulin secretion induced by intravenouly injected secretin, CCK-8 and glucose. However, after vagotomy the inhibitory action of pPP on glucouse-stimulated insulin release disappeared. The present results indicate that PP may play a controlling role in postprandial insulin secretion via vagus from the central nervous system.
- 神戸大学の論文
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