Control of Pancreatic Glucagon Secretion by Glucose

Abstract

Recent questions concerning the role of glucagon as a hormone of “glucose need” prompted this evaluation of glucose-glucagon relationships. To obviate certain problems relating to the sensitivity and specificity of the glucagon radioimmunoassay of peripheral venous plasma, glucagon was assayed in pancreatic venous effluent plasma obtained from conscious dogs with indwelling catheters in the pancreaticoduodenal vein. The effect of change in glucose concentration upon the pancreaticoduodenal vein glucagon concentration was determined. Insulin induced hypoglycemia was uniformly associated with a rise in pancreaticoduodenal vein glucagon concentration to a peak of 5.7 mμg./ml. at thirty minutes. The hyperglucagonemia continued intermittently during the hypoglycemic period but fell promptly during hyperglycemia induced by rapid injection of glucose. Hyperglycemia, induced in fifteen dogs by glucose infusion, was accompanied by a decline of glucagon from 2.7 to 1.8 mμg./ml. Cataglycemia, induced by rapid termination of a glucose infusion, produced a rise of glucagon in three of six dogs. Stimulation of glucagon secretion by hyperaminoacidemia was blocked by hyperglycemia induced by glucose infusion. The effect of starvation upon twenty-four-hour secretion of glucagon could not be determined in these studies. Wide variations in pancreaticoduodenal vein glucagon concentration made meaningful comparison of day-to-day changes impossible. A statistically significant negative correlation was observed between rapidly induced change in plasma glucose concentration and change in pancreaticoduodenal vein glucagon levels. The findings are compatible with the view that glucagon is a hormone of glucose need, which probably functions in the moment-to-moment regulation of blood glucose homeostasis and the maintenance of the so-called “normal” blood glucose limits.

The Effects of Glucagon on Plasma Concentrations of Insulin. Growth Hormone, Glucose and Free Fatty Acids in Sheep: Comparison with the Effects of Catecholamines

“…However, an understanding of the role of glucagon in sheep and in other ruminants must await information about the way the blood glucagon level is regulated. In man and dog, glucagon secretion is stimulated by fasting, hypoglycaemia, hyperaminoacidaemia, and by the gastrointestinal hormone pancreozymin (Unger and Eisentraut 1964;Ohneda et al 1968;Buchanan et al 1969;Ohneda et al 1969;Unger et al 1969) and clearly plays an important role in glucose homeostasis. There have, however, been no comparable studies on ruminants.…”

“…Plasma concentrations of FF A, insulin, and growth hormone were transformed to logarithms (base 10) before calculation of means (Patterson et al 1964;Welborn et al 1966;Wallace and Bassett 1970). For clarity, antilogs of means are used in the presentation of results.…”

Response of extrapancreatic glucagon to glycemic changes under chronic insulin deficiency in dogs.

“…Since hypoglycemia is known to elicit glucagon extrapancreatic glucagon secretion (Ohneda et al 1969), insulin was administered to a group of 5 pancreatectomized dogs in a priming dose of 0.4 U/kg and constant infusion of 0.04 U/kg/min for 120 min followed by a bolus dose of insulin, if necessary. The changes in blood glucose and plasma IRG are shown in Fig, 1.…”

“…There have been, however, a few reports on the secretion of extrapancreatic glucagon, whose presence was demonstrated in 1974. The secretion of pancreatic glucagon is affected by changes in blood glucose (Ohneda et al 1969), and glycemic changes are the most important among the various factors influencing the secretion of pancreatic glucagon. Therefore, we have studied the effect of glycemic changes upon the secretion of extrapancreatic glucagon in animals.…”

Stimulatory and inhibitory effects of cyclic AMP on pancreatic glucagon release from monolayer cultures and the controlling role of calcium

“…The release of the catabolic hormone glucagon is stimulated by stress-associated states [1,2,3,4], physical exercise [5,6,7] and hypoglycemia [8,9,10,11], as well as during infections [12], diabetic ketoacidosis [13,14] and starvation [15,16]. This stimulation of release is caused, at least in part, by activation of the autonomic nervous system.…”