UNIGE document Professional Article
previous document  unige:55460  next document
add to browser collection
Title

Glycoprotein 130 receptor signaling mediates α-cell dysfunction in a rodent model of type 2 diabetes

Authors
Chow, Samuel Z
Speck, Madeleine
Yoganathan, Piriya
Nackiewicz, Dominika
Hansen, Ann Maria
Ladefoged, Mette
Rabe, Björn
Rose-John, Stefan
show hidden authors show all authors [1 - 14]
Published in Diabetes. 2014, vol. 63, no. 9, p. 2984-95
Abstract Dysregulated glucagon secretion accompanies islet inflammation in type 2 diabetes. We recently discovered that interleukin (IL)-6 stimulates glucagon secretion from human and rodent islets. IL-6 family cytokines require the glycoprotein 130 (gp130) receptor to signal. In this study, we elucidated the effects of α-cell gp130 receptor signaling on glycemic control in type 2 diabetes. IL-6 family cytokines were elevated in islets in rodent models of this disease. gp130 receptor activation increased STAT3 phosphorylation in primary α-cells and stimulated glucagon secretion. Pancreatic α-cell gp130 knockout (αgp130KO) mice showed no differences in glycemic control, α-cell function, or α-cell mass. However, when subjected to streptozotocin plus high-fat diet to induce islet inflammation and pathophysiology modeling type 2 diabetes, αgp130KO mice had reduced fasting glycemia, improved glucose tolerance, reduced fasting insulin, and improved α-cell function. Hyperinsulinemic-euglycemic clamps revealed no differences in insulin sensitivity. We conclude that in a setting of islet inflammation and pathophysiology modeling type 2 diabetes, activation of α-cell gp130 receptor signaling has deleterious effects on α-cell function, promoting hyperglycemia. Antagonism of α-cell gp130 receptor signaling may be useful for the treatment of type 2 diabetes.
Keywords AnimalsCytokine Receptor gp130/antagonists & inhibitors/metabolismDiabetes Mellitus, Experimental/physiopathologyDiabetes Mellitus, Type 2/physiopathologyDiet, High-FatGlucagon/secretionGlucagon-Secreting Cells/metabolismInterleukin-6/metabolism/pharmacologyMaleMiceMice, KnockoutPhosphorylationRatsSTAT3 Transcription Factor/metabolism
Identifiers
PMID: 24812426
Full text
Article (Published version) (2.1 MB) - public document Free access
Structures
Research group Types cellulaires pancréatiques pendant l'ontogénèse (522)
Citation
(ISO format)
CHOW, Samuel Z et al. Glycoprotein 130 receptor signaling mediates α-cell dysfunction in a rodent model of type 2 diabetes. In: Diabetes, 2014, vol. 63, n° 9, p. 2984-95. https://archive-ouverte.unige.ch/unige:55460

91 hits

184 downloads

Update

Deposited on : 2015-04-13

Export document
Format :
Citation style :