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Albert Salehi

S Albert Salehi

Research team manager

Albert Salehi

Paradoxical stimulation of glucagon secretion by high glucose concentrations

Author

  • S Albert Salehi
  • Elaine Vieira
  • Erik Gylfe

Summary, in English

Hypersecretion of glucagon contributes to the dysregulation of glucose homeostasis in diabetes. To clarify the underlying mechanism, glucose-regulated glucagon secretion was studied in mouse pancreatic islets and clonal hamster In-R1-G9 glucagon-releasing cells. Apart from the well-known inhibition of secretion with maximal effect around 7 mmol/l glucose, we discovered that mouse islets showed paradoxical stimulation of glucagon release at 25-30 mmol/l and In-R1-G9 cells at 12-20 mmol/l sugar. Whereas glucagon secretion in the absence of glucose was inhibited by hyperpolarization with diazoxide, this agent tended to further enhance secretion stimulated by high concentrations of the sugar. Because U-shaped dose-response relationships for glucose-regulated glucagon secretion were observed in normal islets and in clonal glucagon-releasing cells, both the inhibitory and stimulatory components probably reflect direct effects on the a-cells. Studies of isolated mouse a-cells indicated that glucose inhibited glucagon secretion by lowering the cytoplasmic Ca2+ concentration. However, stimulation of glucagon release by high glucose concentrations did not require elevation of Ca2+, indicating involvement of novel mechanisms in glucose regulation of glucagon secretion. A U-shaped dose-response relationship for glucose-regulated glucagon secretion may explain why diabetic patients with pronounced hyperglycemia display paradoxical hyperglucagonemia.

Department/s

  • Islet cell physiology

Publishing year

2006

Language

English

Pages

2318-2323

Publication/Series

Diabetes

Volume

55

Issue

8

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Islet cell physiology

ISBN/ISSN/Other

  • ISSN: 1939-327X