The Effect of Secretin on the Exocrine and Endocrine Pancreas

Abstract

Previous animal experiments have given contradictory results concerning the effect of secretin on insulin release. The conflicting results are probably due to the fact that the injected hormone was administered in pharmacological amounts not usually attained under physiological conditions in vivo and that the preparation of the secretin used was an extraction which might have contained some other hormones. Moreover, small changes in insulin secretion are reported to remain undetected as the result of hepatic insulin clearance and of the dilution in the peripheral circulation. We have, therefore, investigated the effect of endogenous secretin released by the intraduodenal instillation of HC1 and 1-phenyl-1- hydroxy-n-pentane (PHP), and intravenously infused synthetic secretin in doses which raised portal plasma immunoreactive secretin (IRS) concentrations to those obtained after HC1 and PHP administration on portal plasma immunoreactive insulin (IRI), glucagon (IRG) and glucose concentration. In addition, the effect of somatostatin on IRI and IRG concentrations following acid and PHP administration was investigated by infusing synthetic cyclic somatostatin at the dose of 5 μg/kg/h.Male Wistar rats weighing 240-270g and fasted overnight were used in all experiments. The rats were anesthetized with sodium pentobarbital by a subcutaneous injection. The body temperature was held at 37°C by a heating pad. One of the following solutions was infused into the duodenum at a rate of 2 ml/min for 2 min by means of a micro-tubing pump : 0.1 mo1/1 HC1,200 mg/kg/2 ml PHP and 2.5% arabic gum solution.Blood samples were collected through an indwelling needle inserted into the portal vein in the direction of the venous blood flow at 0, 5, 10, 15, 20 and 30 min after the initiation of the infusion. The samples were centrifuged at 4°C, and plasma was stored at - 20°C until assayed.IRI was measured by polyethylene glycol radioimmunoassay. IRG was determined by radioimmunoassay by means of a talc absorption technique using antiserum 30K. Rat insulin and porcine glucagon were used as standards in the IRI and IRG assay, respectively. Glucose concentrations were measured by the glucose oxidase method with a Toshiba LAC-02A glucose analyzer.Although there was a rapid rise in serum IRS concentrations at 5 min after the administration of HCl and PHP, no significant changes in IRI concentrations were elicited by these stimuli. By contrast, IRG concentrations were significantly increased at 30 min after the intraduodenal infusion of HC1.Constant infusion of somatostatin did not influence either IRI or IRG levels during intraduodenal stimulation with HCl and PHP, but it profoundly inhibited the HC1-induced IRG increase.When synthetic secretin was infused to elevate the portal plasma IRS levels up to the same levels as those after HCl or PHP, no changes in the levels of IRI and IRG in the portal venous blood were observed.The present observations with direct intraduodenal instillation of acid and PHP in quantitites sufficient to produce significant elevations of portal venous IRS concentrations did not result in an elevation of portal plasma IRI levels. In addition, the administration of physiological quantities of synthetic secretin failed to elicite any effect on portal IRI levels. It is therefore unlikely that secretin is responsible for entero-insular axis.