Effect of Glucose and Insulin on Glucagon Secretion in Alloxan Diabetic Rats

Abstract

Plasma glucagon (IRG) response to different glucose levels in alloxan diabetic rats was studied. Glucose was given to normal and diabetic rats orally and then by infusion, and the amount of IRG secreted was measured. The experiment was also done on isolated rat pancreas which was perfused with glucose. Oral glucose load (0.3 g/100 g) produced a paradoxical rise in IRG in alloxan diabetic rats while no significant change was observed in normal rats. When glucose was infused (0.15 g/100 g as a bolus + 0.006 g/100 g/min) IRG secretion was inhibited over the entire period of the test in both normal and diabetic rats, but the inhibition observed in diabetic rats was weaker. However, in the isolated rat pancreas perfusion experiment, alloxan diabetic rat pancreas responded normally to increasing glucose concentration resulting in a decrease of IRG in the perfusate. When insulin was infused in vivo into diabetic rats that were given glucose orally, the paradoxical rise in IRG was prevented. In the case of rats that were given glucose by infusion, the addition of insulin lowered IRG levels. On the other hand, when glucose level was decreased to the state of hypoglycemia, a significant increase in IRG was observed in both normal and diabetic rats. From these results it is concluded that 1) paradoxical rise of IRG during oral glucose load is related to IRG secreted from gut in addition to that secreted from pancreas, 2) excess glucagon secretion from pancreas in alloxan diabetic rats can be inhibited by administrating large amount of insulin, however, 3) in the in vitro perfusion system, glucagon secretion was not influenced by insulin deficiency.

Effect of Diabetes Mellitus on the Regulation of Enzyme Secretion by Isolated Rat Pancreatic Acini

“…Thus, many of the exocrine pancreatic abnormalities in diabetes may be directly due to insulin deficiency. However, the role of structural changes in either the pancreatic vasculature or pancreatic parenchymal tissue (6-8, 35, 36), and changes in other hormones such as glucagon (37,38), somatostatin (39,40), and pancreatic polypeptide (41,42) remain to be assessed. Furthermore, the reduced output of pancreatic bicarbonate in human diabetic (3,4) suggests that pancreatic ductular functions as well as acinar function are abnormal.…”