Vladimir Grubelnik (Author), Jan Zmazek (Author), Rene Markovič (Author), Marko Gosak (Author), Marko Marhl (Author)

Abstract

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.

Keywords

endokrine celice trebušne slinavke;matematični modeli;mitohondrijska disfunkcija;celularna bioenergetika;diabetes;glukagon;inzulin;ne zaključna dela;pancreatic endocrine cells;mathematical model;mitochondrial dysfunction;cellular bioenergetics;glucagon;insulin;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UM FNM - Faculty of Natural Sciences and Mathematics
Publisher: MDPI
UDC: 616.379
COBISS: 43234819 Link will open in a new window
ISSN: 2075-1729
Views: 47
Downloads: 12
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Other data

Secondary language: Slovenian
Secondary keywords: Sladkorna bolezen;Matematični modeli;
Type (COBISS): Scientific work
Pages: str. 1-16
Volume: ǂVol. ǂ10
Issue: ǂno. ǂ12
Chronology: 2020
DOI: 10.3390/life10120348
ID: 24893142