A computational systems analysis of factors regulating α cell glucagon secretion

Fridlyand, Leonid E.; Philipson, Louis H.

doi:10.4161/isl.22193

Cited by 12Pancreatic function and diabetesIon channel regulation and functionDiabetes Treatment and Management

A computational systems analysis of factors regulating α cell glucagon secretion

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Fridlyand, Leonid E., Philipson, Louis H.·2012·Islets

DOI 10.4161/isl.22193PMC PMC3496652

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Abstract

Glucagon, a peptide hormone secreted from the α-cells of the pancreatic islets, is critical for blood glucose homeostasis. We reviewed the literature and employed a computational systems analysis of intracellular metabolic and electrical regulation of glucagon secretion to better understand these processes. The mathematical model of α-cell metabolic parameters is based on our previous model for pancreatic β-cells. We also formulated an ionic model for action potentials that incorporates Ca ( 2+) , K (+) , Na (+) and Cl (-) currents. Metabolic and ionic models are coupled to the equations describing Ca ( 2+) homeostasis and glucagon secretion that depends on activation of specific voltage-gated Ca ( 2+) channels. Paracrine and endocrine regulations were analyzed with an emphasis on their effects on a hyperpolarization of membrane potential. This general model simulates and gives insight into the mechanisms of regulation of glucagon secretion under a wide range of experimental conditions. We also reviewed and analyzed dysfunctional mechanisms in α-cells to determine key pharmacological targets for modulating glucagon secretion in type 1 and 2 diabetes.

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A relatively large set of mathematical models were developed with focus on glucagon secretion at cellular level.
“A relatively large set of mathematical models were developed with focus on glucagon secretion at cellular level (12–21).”
From Mathematical Model of Glucagon Kinetics for the Assessment of Insulin-Mediated Glucagon Inhibition During an Oral Glucose Tolerance Test (2021) · cites this paper as [21]
Section 2.5 describes this paper’s computational model of glucagon secretion in α-cells, so it is an example of the kind of model cited. But Section 4.6 says the authors found only two earlier intracellular α-cell models and that neither simulated glucagon secretion; this paper does not support the claim that a relatively large set had been developed. (LLM, conf=0.88)
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Authors: Fridlyand, L. E., & Philipson, L. H.
Affiliations: University of Chicago (US)
Corresponding author: Fridlyand, Leonid E.
ORCID: Fridlyand, Leonid E.
Philipson, Louis H.
Venue: Islets
Publisher: Informa UK Limited
Published: 2012-07
Volume: 4
Issue: 4
Pages: 262-283
ISSN: 1938-2014 (ISSN-L)
1938-2022
DOI: 10.4161/isl.22193
PMC: PMC3496652
OpenAlex: W2052359704
Cited by: 12
References: 127
Citations by year: 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 2
FWCI: 0.98
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
Locations: Islets (publishedVersion, cc-by-nc)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (DK-063493, R01DK048494, R01DK063493, DK-48494, P60DK020595)
Topics: Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords: glucagon secretion, alpha cells, pancreatic islets, glucose homeostasis, cellular metabolism, voltage-gated calcium channels, calcium homeostasis, membrane hyperpolarization, paracrine regulation, hormonal regulation, type 1 diabetes, type 2 diabetes, therapeutic target
MeSH terms: Animals, Biological Transport, Calcium, Computer Simulation, Diabetes Mellitus, Glucagon, Glucose, Hormones, Humans, Membrane Potentials, Models, Biological, Calcium Channels, Potassium Channels, Chloride Channels, Paracrine Communication, Systems Biology, Glucagon-Secreting Cells, Electrophysiological Phenomena

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A computational systems analysis of factors regulating α cell glucagon secretion

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