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Glucose controls glucagon secretion by directly modulating cAMP in alpha cells
Qian Yu1, Hongyan Shuai1, Parvin Ahooghalandari1
1Department of Medical Cell Biology, Biomedical Centre, Uppsala University, Box 571, SE-751 23, Uppsala, Sweden.
Diabetologia
|April 7, 2019
Summary
Low glucose directly increases cyclic AMP (cAMP) in alpha cells, stimulating glucagon secretion independently of other hormones. This mechanism is vital for preventing hypoglycemia and may be impaired in diabetes.
Area of Science:
- Endocrinology
- Metabolism
- Cell Biology
Background:
- Glucagon is essential for glucose homeostasis, but its secretion regulation by glucose in pancreatic alpha cells is not fully understood.
- Aberrant glucagon secretion contributes to poor glucose control in diabetes.
Purpose of the Study:
- To investigate the role of cyclic AMP (cAMP) in alpha cell-intrinsic glucose regulation of glucagon release.
- To elucidate the mechanisms by which glucose controls glucagon secretion.
Main Methods:
- Measured subplasmalemmal cAMP and Ca2+ concentrations in isolated alpha cells using fluorescent reporters and total internal reflection microscopy.
- Quantified glucagon secretion from mouse islets using ELISA.
Main Results:
- Glucose induced Ca2+-independent changes in alpha cell cAMP that correlated with glucagon release.
- Elevated cAMP, independent of paracrine signals, stimulated glucagon secretion and overrode glucose inhibition.
- Protein kinase A inhibition mimicked glucose-induced suppression of glucagon release.
Conclusions:
- Hypoglycemic glucose levels directly regulate glucagon secretion by modulating alpha cell cAMP, independent of paracrine factors.
- This novel mechanism is crucial for recovery from hypoglycemia and may be disrupted in diabetes.
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