Cited by 15Pancreatic function and diabetesMetabolism, Diabetes, and CancerDiabetes Treatment and Management

Modelling of energy-driven switch for glucagon and insulin secretion

Grubelnik, Vladimir, Zmazek, Jan, Markovič, Rene, Gosak, Marko, Marhl, Marko·2020·Journal of Theoretical Biology

Abstract

We present a mathematical model of the energy-driven metabolic switch for glucagon and insulin secretion from pancreatic alpha and beta cells, respectively. The energy status related to hormone secretion is studied for various glucose concentrations. Additionally, the physiological response is studied with regards to the presence of other metabolites, particularly the free-fatty acids. At low glucose, the ATP production in alpha cells is high due to free-fatty acids oxidation in mitochondria, which enables glucagon secretion. When the glucose concentration is elevated above the threshold value, the glucagon secretion is switched off due to the contribution of glycolytic ATP production, representing an "anaerobic switch". On the other hand, during hypoglycemia, the ATP production in beta cells is low, reflecting a "waiting state" for glucose as the main metabolite. When glucose is elevated above the threshold value, the oxidative fate of glucose in mitochondria is the main source of energy required for effective insulin secretion, i.e. the "aerobic switch". Our results show the importance of well-regulated and fine-tuned energetic processes in pancreatic alpha and beta cells required for efficient hormone secretion and hence effective blood glucose regulation. These energetic processes have to be appropriately switched on and off based on the sensing of different metabolites by alpha and beta cells. Our computational results indicate that disturbances in cell energetics (e.g. mitochondrial dysfunction), and dysfunctional metabolite sensing and distribution throughout the cell might be related to pathologies such as metabolic syndrome and diabetes.

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Crossref · 10.1016/j.jtbi.2020.110213

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Authors
Grubelnik, V., Zmazek, J., Markovič, R., Gosak, M., & Marhl, M.
Affiliations
University of Maribor (SI)
Corresponding author
Marhl, Marko
Venue
Journal of Theoretical Biology
Publisher
Elsevier BV
Published
2020-05
Volume
493
Pages
110213
ISSN
0022-5193 (ISSN-L)
OpenAlex
W3007379472
Cited by
15
References
110
Citations by year
2026: 1 · 2025: 1 · 2024: 3 · 2022: 4 · 2021: 3 · 2020: 3
FWCI
2.28
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Theoretical Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Javna Agencija za Raziskovalno Dejavnost RS (P1-0055, P3-0396)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
glucagon secretion, insulin secretion, alpha cells, pancreatic beta cells, ATP production, free fatty acid oxidation, glycolysis, glucose threshold, hypoglycemia, mitochondrial dysfunction, blood glucose regulation, metabolic syndrome, diabetes mellitus
MeSH terms
Insulin Secretion, Glucagon, Glucose, Humans, Hypoglycemia, Insulin

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