In beta-cells, mitochondria integrate and generate metabolic signals controlling insulin secretion
Abstract
Pancreatic beta-cells are unique neuroendocrine cells displaying the peculiar feature of responding to nutrients, principally glucose, as primary stimulus. This requires translation of a metabolic substrate into intracellular messengers recognized by the exocytotic machinery. Central to this signal transduction mechanism, mitochondria integrate and generate metabolic signals, thereby coupling glucose recognition to insulin secretion. In response to a glucose rise, nucleotides and metabolites are generated by mitochondria and participate, together with cytosolic calcium, to the stimulation of insulin exocytosis. This review describes the mitochondrion-dependent pathways of regulated insulin secretion. In particular, importance of cataplerotic and anaplerotic processes is discussed, with special attention to the mitochondrial enzyme glutamate dehydrogenase. Mitochondrial defects, such as mutations and reactive oxygen species production, are presented in the context of beta-cell failure in the course of type 2 diabetes.
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Clonal cytosolic hybrid cells harboring mitochondria derived from MIDD patients exhibit impaired calcium handling and elevated ROS under metabolic stress.
“Consistent with this view, clonal cytosolic hybrid cells harboring mitochondria derived from MIDD patients exhibit impaired calcium handling and elevated ROS under metabolic stress (247, 248).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [247]
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The role of mitochondria in the pathogenesis of type 2 diabetes
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Dopamine-mediated autocrine inhibition of insulin secretion
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“Then, we explored the effect of dopamine on insulin secretion induced by glucose and other secreta-gogues acting with different mechanisms (Maechler et al., 2006; Merrins et al., 2022).”
- Authors
- Maechler, P., Carobbio, S., & Rubi, B.
- Affiliations
- University of Geneva (CH)
- Corresponding author
- Maechler, Pierre
- Venue
- The International Journal of Biochemistry & Cell Biology
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 38
- Issue
- 5-6
- Pages
- 696-709
- ISSN
- 1357-2725 (ISSN-L)
- OpenAlex
- W2104595034
- Cited by
- 140
- References
- 153
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 3 · 2017: 6 · 2016: 9 · 2015: 4 · 2014: 10 · 2013: 3 · 2012: 12
- FWCI
- 2.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The International Journal of Biochemistry & Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- pancreatic beta cells, insulin secretion, mitochondria, glucose detection, metabolic signaling, insulin exocytosis, cataplerosis, anaplerosis, glutamate dehydrogenase, intracellular calcium, reactive oxygen species, mitochondrial mutations, type 2 diabetes, beta-cell failure
- MeSH terms
- Insulin Secretion, Adenosine Triphosphate, Animals, Diabetes Mellitus, Type 2, Exocytosis, Glutamate Dehydrogenase, Humans, Insulin, Mitochondria, NAD, Signal Transduction, Pyruvic Acid, Electron Transport Chain Complex Proteins, Insulin-Secreting Cells
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