Cited by 53Pancreatic function and diabetesDiabetes Treatment and ManagementDiabetes and associated disorders

Paracrine regulation of glucagon secretion: the β/α/δ model

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Watts, Margaret, Ha, Joon, Kimchi, Ofer, Sherman, Arthur·2016·American Journal of Physiology-Endocrinology and Metabolism

Abstract

The regulation of glucagon secretion in the pancreatic α-cell is not well understood. It has been proposed that glucose suppresses glucagon secretion either directly through an intrinsic mechanism within the α-cell or indirectly through an extrinsic mechanism. Previously, we described a mathematical model for isolated pancreatic α-cells and used it to investigate possible intrinsic mechanisms of regulating glucagon secretion. We demonstrated that glucose can suppress glucagon secretion through both ATP-dependent potassium channels (K ATP ) and a store-operated current (SOC). We have now developed an islet model that combines previously published mathematical models of α- and β-cells with a new model of δ-cells and use it to explore the effects of insulin and somatostatin on glucagon secretion. We show that the model can reproduce experimental observations that the inhibitory effect of glucose remains even when paracrine modulators are no longer acting on the α-cell. We demonstrate how paracrine interactions can either synchronize α- and δ-cells to produce pulsatile oscillations in glucagon and somatostatin secretion or fail to do so. The model can also account for the paradoxical observation that glucagon can be out of phase with insulin, whereas α-cell calcium is in phase with insulin. We conclude that both paracrine interactions and the α-cell's intrinsic mechanisms are needed to explain the response of glucagon secretion to glucose.

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Authors
Watts, M., Ha, J., Kimchi, O., & Sherman, A.
Affiliations
  • National Institutes of Health (US)
  • Princeton University (US)
Corresponding author
Sherman, Arthur
Venue
American Journal of Physiology-Endocrinology and Metabolism
Published
2016-04-15
Volume
310
Issue
8
Pages
E597-E611
ISSN
  • 0193-1849 (ISSN-L)
  • 1522-1555
OpenAlex
W2300512885
Cited by
53
References
84
Citations by year
2026: 5 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 9 · 2021: 9 · 2020: 7 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 1
FWCI
4.80
Type
journal article
Language
en
Open access
Locations
  • American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
  • PubMed Central (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, paracrine regulation, delta cells, pancreatic beta cells, ATP-sensitive potassium channels, insulin, somatostatin, pulsatile secretion, mathematical model
MeSH terms
Calcium, Glucagon, Glucose, Humans, Insulin, Models, Theoretical, Somatostatin, Somatostatin-Secreting Cells, Paracrine Communication, Glucagon-Secreting Cells, Insulin-Secreting Cells

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