Mitochondrial Dysfunction in Pancreatic Alpha and Beta Cells Associated with Type 2 Diabetes Mellitus
Type 2 diabetes mellitus is a complex multifactorial disease of epidemic proportions. It involves genetic and lifestyle factors that lead to dysregulations in hormone secretion and metabolic homeostasis. Accumulating evidence indicates that altered mitochondrial structure, function, and particularly...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/10/12/348 |
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| author | Vladimir Grubelnik Jan Zmazek Rene Markovič Marko Gosak Marko Marhl |
| author_facet | Vladimir Grubelnik Jan Zmazek Rene Markovič Marko Gosak Marko Marhl |
| author_sort | Vladimir Grubelnik |
| collection | DOAJ |
| description | Type 2 diabetes mellitus is a complex multifactorial disease of epidemic proportions. It involves genetic and lifestyle factors that lead to dysregulations in hormone secretion and metabolic homeostasis. Accumulating evidence indicates that altered mitochondrial structure, function, and particularly bioenergetics of cells in different tissues have a central role in the pathogenesis of type 2 diabetes mellitus. In the present study, we explore how mitochondrial dysfunction impairs the coupling between metabolism and exocytosis in the pancreatic alpha and beta cells. We demonstrate that reduced mitochondrial ATP production is linked with the observed defects in insulin and glucagon secretion by utilizing computational modeling approach. Specifically, a 30–40% reduction in alpha cells’ mitochondrial function leads to a pathological shift of glucagon secretion, characterized by oversecretion at high glucose concentrations and insufficient secretion in hypoglycemia. In beta cells, the impaired mitochondrial energy metabolism is accompanied by reduced insulin secretion at all glucose levels, but the differences, compared to a normal beta cell, are the most pronounced in hyperglycemia. These findings improve our understanding of metabolic pathways and mitochondrial bioenergetics in the pathology of type 2 diabetes mellitus and might help drive the development of innovative therapies to treat various metabolic diseases. |
| first_indexed | 2024-03-10T14:05:29Z |
| format | Article |
| id | doaj.art-0056af75bf114277afecbe6e67ef26c6 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T14:05:29Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-0056af75bf114277afecbe6e67ef26c62023-11-21T00:42:00ZengMDPI AGLife2075-17292020-12-01101234810.3390/life10120348Mitochondrial Dysfunction in Pancreatic Alpha and Beta Cells Associated with Type 2 Diabetes MellitusVladimir Grubelnik0Jan Zmazek1Rene Markovič2Marko Gosak3Marko Marhl4Faculty of Electrical Engineering and Computer Science, University of Maribor, SI-2000 Maribor, SloveniaFaculty of Natural Sciences and Mathematics, University of Maribor, SI-2000 Maribor, SloveniaFaculty of Electrical Engineering and Computer Science, University of Maribor, SI-2000 Maribor, SloveniaFaculty of Natural Sciences and Mathematics, University of Maribor, SI-2000 Maribor, SloveniaFaculty of Natural Sciences and Mathematics, University of Maribor, SI-2000 Maribor, SloveniaType 2 diabetes mellitus is a complex multifactorial disease of epidemic proportions. It involves genetic and lifestyle factors that lead to dysregulations in hormone secretion and metabolic homeostasis. Accumulating evidence indicates that altered mitochondrial structure, function, and particularly bioenergetics of cells in different tissues have a central role in the pathogenesis of type 2 diabetes mellitus. In the present study, we explore how mitochondrial dysfunction impairs the coupling between metabolism and exocytosis in the pancreatic alpha and beta cells. We demonstrate that reduced mitochondrial ATP production is linked with the observed defects in insulin and glucagon secretion by utilizing computational modeling approach. Specifically, a 30–40% reduction in alpha cells’ mitochondrial function leads to a pathological shift of glucagon secretion, characterized by oversecretion at high glucose concentrations and insufficient secretion in hypoglycemia. In beta cells, the impaired mitochondrial energy metabolism is accompanied by reduced insulin secretion at all glucose levels, but the differences, compared to a normal beta cell, are the most pronounced in hyperglycemia. These findings improve our understanding of metabolic pathways and mitochondrial bioenergetics in the pathology of type 2 diabetes mellitus and might help drive the development of innovative therapies to treat various metabolic diseases.https://www.mdpi.com/2075-1729/10/12/348pancreatic endocrine cellsmathematical modelmitochondrial dysfunctioncellular bioenergeticsdiabetesglucagon |
| spellingShingle | Vladimir Grubelnik Jan Zmazek Rene Markovič Marko Gosak Marko Marhl Mitochondrial Dysfunction in Pancreatic Alpha and Beta Cells Associated with Type 2 Diabetes Mellitus Life pancreatic endocrine cells mathematical model mitochondrial dysfunction cellular bioenergetics diabetes glucagon |
| title | Mitochondrial Dysfunction in Pancreatic Alpha and Beta Cells Associated with Type 2 Diabetes Mellitus |
| title_full | Mitochondrial Dysfunction in Pancreatic Alpha and Beta Cells Associated with Type 2 Diabetes Mellitus |
| title_fullStr | Mitochondrial Dysfunction in Pancreatic Alpha and Beta Cells Associated with Type 2 Diabetes Mellitus |
| title_full_unstemmed | Mitochondrial Dysfunction in Pancreatic Alpha and Beta Cells Associated with Type 2 Diabetes Mellitus |
| title_short | Mitochondrial Dysfunction in Pancreatic Alpha and Beta Cells Associated with Type 2 Diabetes Mellitus |
| title_sort | mitochondrial dysfunction in pancreatic alpha and beta cells associated with type 2 diabetes mellitus |
| topic | pancreatic endocrine cells mathematical model mitochondrial dysfunction cellular bioenergetics diabetes glucagon |
| url | https://www.mdpi.com/2075-1729/10/12/348 |
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