Glucose or Insulin, but not Zinc Ions, Inhibit Glucagon Secretion From Mouse Pancreatic α-Cells
Abstract
The mechanisms by which hypoglycemia stimulates glucagon release are still poorly understood. In particular, the relative importance of direct metabolic coupling versus paracrine regulation by β-cell secretory products is unresolved. Here, we compare the responses to glucose of 1) α-cells within the intact mouse islet, 2) dissociated α-cells, and 3) clonal αTC1-9 cells. Free cytosolic concentrations of ATP ([ATP]c) or Ca2+ ([Ca2+]c) were imaged using α-cell–targeted firefly luciferase or a green fluorescent protein–based Ca2+ probe (“pericam”), respectively. Consistent with a direct effect of glucose on α-cell oxidative metabolism, an increase in glucose concentration (from 0 or 3 mmol/l to 20 mmol/l) increased [ATP]c by 7–9% in α-cells within the intact islet and by ∼4% in αTC1-9 cells. Moreover, glucose also dose-dependently decreased the frequency of [Ca2+]c oscillations in both dissociated α-cells and αTC1-9 cells. Although the effects of glucose were mimicked by exogenous insulin, they were preserved when insulin signaling was blocked with wortmannin. Addition of ZnCl2 slightly increased the frequency of [Ca2+]c oscillations but failed to affect glucagon release from either islets or αTC1-9 cells under most conditions. We conclude that glucose and insulin, but not Zn2+ ions, independently suppress glucagon secretion in the mouse.
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Glucose inhibits glucagon secretion from clonal glucagon-releasing cells.
“Glucose inhibits glucagon secretion from clonal glucagonreleasing cells [5,11,17]”
From Glucose inhibits glucagon secretion by a direct effect on mouse pancreatic alpha cells (2007) · cites this paper as [17]
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- Authors
- Ravier, M. A., & Rutter, G. A.
- Affiliations
- University of Bristol (GB)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2005-06-01
- Volume
- 54
- Issue
- 6
- Pages
- 1789-1797
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2166243077
- Cited by
- 264
- References
- 55
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 8 · 2022: 9 · 2021: 17 · 2020: 10 · 2019: 8 · 2018: 9 · 2017: 11 · 2016: 14 · 2015: 9 · 2014: 20 · 2013: 16 · 2012: 16
- FWCI
- 14.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- glucagon secretion, alpha cells, glucose, insulin, zinc ions, hypoglycemia, calcium oscillations, ATP, wortmannin, insulin signaling, islets, paracrine regulation, metabolic coupling
- MeSH terms
- Adenosine Triphosphate, Animals, Calcium, Cell Line, Cells, Cultured, Clone Cells, Glucagon, Glucose, Insulin, Islets of Langerhans, Zinc, Mice
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