Insulin within islets is a physiologic glucagon release inhibitor.
Reads0
Chats0
TLDR
It is concluded that insulin maintains an ongoing restraint upon alpha cell secretion and in its absence causes hectic hypersecretion of glucagon, which probably occurs largely in the intravascular compartment.Abstract:
To determine if glucagon secretion is under physiological control of intra-islet insulin, pancreata from normal rats were perfused at a 100 mg/dl glucose concentration with either guinea pig antiinsulin serum or normal guinea pig serum in a nonrecirculating system. Perfusion of antiserum was followed within 3 min by a significant rise in glucagon that reached peak levels three times the base-line values and assumed a hectic pattern that returned rapidly to base-line levels upon termination of the antiserum perfusion. Nonimmune guinea pig serum had no effect. To gain insight into the probable site of insulin neutralization, 125I-labeled human gamma-globulin was added to antiserum or nonimmune serum and perfused for 3 min. More than 83% of the radioactivity was recovered in the effluent within 3 min after termination of the infusion, and only 0.05 +/- 0.015% of the radioactivity injected was present in the pancreas 10 min after the perfusion. The maximal amount of insulin that could be completely bound to insulin antibody at a dilution and under conditions simulating those of the perfusion experiments was 20 mU/min. It is concluded that insulin maintains an ongoing restraint upon alpha cell secretion and in its absence causes hectic hypersecretion of glucagon. This restraint probably occurs largely in the intravascular compartment. Loss of this release-inhibiting action of insulin may account for initiation of hyperglucagonemia in insulin-deficient states.read more
Citations
More filters
Journal ArticleDOI
Endocrine Regulation of Energy Metabolism by the Skeleton
Na Kyung Lee,Hideaki Sowa,Eiichi Hinoi,Mathieu Ferron,Jong Deok Ahn,Cyrille Confavreux,Romain Dacquin,Patrick J. Mee,Marc D. McKee,Dae Young Jung,Zhiyou Zhang,Jason K. Kim,Franck Mauvais-Jarvis,Patricia Ducy,Gerard Karsenty +14 more
TL;DR: It is shown that mice lacking the protein tyrosine phosphatase OST-PTP are hypoglycemic and are protected from obesity and glucose intolerance because of an increase in beta-cell proliferation, insulin secretion, and insulin sensitivity, and in vivo osteocalcin can improve glucose tolerance.
Journal ArticleDOI
Mechanisms of Insulin Action and Insulin Resistance
TL;DR: This work aims to develop an integrated physiological perspective, placing the intricate signaling effectors that carry out the cell-autonomous response to insulin in the context of the tissue-specific functions that generate the coordinated organismal response.
Journal ArticleDOI
Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients
Ele Ferrannini,Elza Muscelli,Silvia Frascerra,Simona Baldi,Andrea Mari,Tim Heise,Uli C. Broedl,Hans-Juergen Woerle +7 more
TL;DR: In patients with type 2 diabetes, empagliflozin-induced glycosuria improved β cell function and insulin sensitivity, despite the fall in insulin secretion and tissue glucose disposal and the rise in EGP after one dose, thereby lowering fasting and postprandial glycemia.
Journal ArticleDOI
Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover.
TL;DR: It is concluded that glucose-responsive β cells normally regulate juxtaposed α cells and that without intraislet insulin, unregulated α cells hypersecrete glucagon, which directly causes the symptoms of diabetes, indicating that glucagon suppression or inactivation may provide therapeutic advantages over insulin monotherapy.
Journal ArticleDOI
Alpha-cells of the endocrine pancreas: 35 years of research but the enigma remains.
TL;DR: The islet cell composition and organization are described in different species and serve as a basis for understanding how the numerous paracrine, hormonal, and nervous signals fine-tune glucagon secretion under different physiological conditions.
References
More filters
Journal ArticleDOI
Coated charcoal immunoassay of insulin.
TL;DR: The procedure here described yields a straight line graph when insulin added is plotted against insulin recovered, and makes simpler and more rapid the immunoassay of insulin in biologic fluids, using radioisotope dilution with 131I-insulin and "biopsy" of the insulin pool by antibody to insulin.
Journal ArticleDOI
Immunoassay of endogenous plasma insulin in man
TL;DR: The insulin concentration in plasma has been estimated from the degree of hypoglycemia produced in hypophysectomized, adrenalectomization, alloxan-diabetic rats, and from the increased oxidation of glucose-1-C14 by the rat epididymal fat pad.
Journal ArticleDOI
Studies of pancreatic alpha cell function in normal and diabetic subjects
TL;DR: The findings suggest that alpha cell function is inappropriately increased in diabetes mellitus and could play a significant role in the diabetic syndrome.
Journal ArticleDOI
New Perspectives on the Microvasculature of the Islets of Langerhans in the Rat
Susan Bonner-Weir,L Orci +1 more
TL;DR: The vasculature of the islets of Langerhans was studied in rats using methacrylate corrosion casts and islet reconstructions from stained serial paraffin sections as discussed by the authors.
Journal ArticleDOI
The effect of experimental insulin deficiency on glucagon secretion
TL;DR: It is concluded that normal suppression of glucagon secretion by hyperglycemia does not occur when glucose metabolism is blocked or when severe insulin deficiency is produced, and it is suggested that normal glucose metabolism within the alpha cell may be an insulin-requiring process without which hyperglycemic suppressed glucagon release cannot occur.
Related Papers (5)
New Perspectives on the Microvasculature of the Islets of Langerhans in the Rat
Susan Bonner-Weir,L Orci +1 more