H Laube

Hyperglucagonemia of the isolated perfused pancreas of diabetic mice (db/db)

SummaryDiabetes mellitus is held to be accompanied by inappropriately high levels of plasma glucagon relative to blood glucose concentrations. This has been interpreted as indicating lack of insulin. To establish glucagon release in presence of high levels of endogenous insulin, the effects of both glucose and arginine were studied in the isolated perfused pancreas of genetically diabetic mice (db/db). Stimulation with glucose 2.75 mM or glucose plus arginine 8.25 mM exhibited a pronounced hyperglucagonemia. Following glucose 8.25 mM, however, there was no depression of glucagon secretion. Despite excessive high levels of endogenous insulin, there was a pattern of rather non-suppressible glucagon release. Lack of insulin per se, therefore, is unlikely to be the sole cause of hyperglucagonemia in this type of genetic animal diabetes mellitus.

Insulin secretion and biosynthesis in sucrose fed rats

SummaryLong term feeding of a sucrose rich diet to rats is accompanied by a decreased glucose assimilation rate, despite high plasma insulin levels. Hyperinsulinism is at least partially based on a relative obesity, with increased amounts of abdominal- and retroperitoneal fat tissue, but unchanged total body weight compared to starch fed controls. The secretory pattern of insulin release was studied following glucose, arginine, fructose and sulfonylurea administration in the isolated perfused pancreas of sucrose and isocaloric starch fed rats. In addition, isolated islets of Langerhans were used to demonstrate the effects of glucose on insulin secretion and the incorporation of H-3 leucine into the proinsulin and insulin fraction of islet proteins. Following 11 mM glucose, the dynamics of insulin release in the isolated perfused pancreas of sucrose fed rats is characterized by a markedly elevated, late plateau-like response, usually seen only at higher glucose concentrations. Hyperinsulinism, as compared to starch fed controls, can also be demonstrated following arginine and the sulfonylurea HB-419, whereas fructose has no effect in the presence of low glucose concentrations. During incubation of the pancreatic islets, the hyperinsulinism in sucrose-, compared to starch fed rats, is more pronounced at 11 mM glucose than at 5.5 mM glucose. The incorporation of H-3 leucine into the proinsulin-insulin fraction of islet proteins in sucrose compared to starch fed rats, however, is significantly greater with glucose 5.5 mM than at high glucose level. In sucrose fed rats, secretion and biosynthesis of insulin thus appear to be elevated but closely linked only at physiological glucose concentration.

Influence of atropine on the insulin secretion in man induced by intestinal hormones

Summary and ConclusionsIn 35 metabolically normal subjects the effect of i.v. secretin and cholecystokinin-pancreozymin (CCK/PZ) on the endocrine and exocrine pancreatic function was investigated, before and after atropine. In addition, the effect of oral, intravenous and intraduodenal administration of glucose and amino acids on blood sugar and free fatty acids before and after the injection of atropine was studied.The secretin stimulated endocrine and exocrine pancreas was not affected by atropine. However, atropine inhibited the ecbolic and endocrine pancreatic function after stimulation with CCK/PZ. Therefore, the effect of i.v. CCK/PZ seems to be mediated by the cholinergic system, or even a “neuro-hormonal” system which acts synergically or additively.No influence of atropine on the insulin secretion induced by i.v. glucose or amino acids was observed. On the other hand, atropine inhibited the beta-cytotropic effect of glucose and amino acids after oral or intraduodenal administration.These findings indicate that the release of these intestinal hormones is dependent on the cholinergic or parasympathetic system.Zusammenfassung und SchluβfolgerungBei 35 stoffwechselgesunden freiwilligen Probanden wurde vor sowie nach Atropingabe die Wirkung der intestinalen Hormone Sekretin und Cholecystokinin-Pankreozymin (CCK-PZ) auf die endokrine und exokrine Pankreasfunktion untersucht. Außerdem wurde die Wirkung von intravenös und oral bzw. intraduodenal verabreichter Glucose und Aminosäuren auf die Insulinsekretion, den Blutzucker und die freien Fettsäuren ebenfalls vor und nach Atropinmedikation geprüft.Intravenös verabreichtes Sekretin konnte weder in seiner exokrinen noch endokrinen Pankreasfunktion durch Atropin beeinflußt werden. Intravenös injiziertes CCK-PZ konnte mittels Atropin sowohl in seiner ekbolischen wie auch endokrinen Pankreasfunktion gehemmt werden. Die Wirkung von CCK-PZ ist somit an ein cholinerges System gebunden, so daß es erlaubt erscheint, bezüglich der Pankreozyminwirkung von einem synergistisch bzw. additiv wirksam werdenden „neurohormonalen“ Mechanismus zu sprechen.Die durch parenteral verabreichte Glucose oder Aminosäuren induzierte Insulinsekretion wurde durch Atropin nicht beeinflußt; hingegen hemmte Atropin dieβ-cytotrope Wirkung von oral bzw. intraduodenal verabreichter Glucose oder Aminosäuren. Dies läßt auf eine Abhängigkeit von einem cholinergen oder parasympathischen System in der Freisetzung dieser intestinalen Hormone schließen.