20.500.12556/DKUM-90137 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 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. pancreatic endocrine cells mathematical model mitochondrial dysfunction cellular bioenergetics diabetes glucagon insulin endokrine celice trebušne slinavke matematični model mitohondrijska disfunkcija celična bioenergetika diabetes glukagon inzulin true true true MDPI Angleški jezik Slovenski jezik Znanstveno delo 2024-08-23 04:16:10 2024-09-03 08:38:16 2025-01-23 11:01:25 0000-00-00 00:00:00 2020 0 0 Str. 1-16 št. 12, št. članka 348 Letn. 10 2020 0000-00-00 Zaloznikova Objavljeno apc 2020-10-23 2020-12-10 2020-12-14 616.379 43234819 10.3390/life10120348 2075-1729 RAZ_Grubelnik_Vladimir_2020.pdf RAZ_Grubelnik_Vladimir_2020.pdf 1 715A06CE86DE8D71511B4477A6F3222E 2900be563684ab9ee9c8ff26eee91ff6c80a63e6742a951dad56a81995f39124 890d7dea-69be-11ef-af22-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=184155 https://doi.org/10.3390/life10120348 0 b451d07d-60f5-11ef-84e9-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=183131 Fakulteta za elektrotehniko, računalništvo in informatiko Fakulteta za naravoslovje in matematiko Medicinska fakulteta Pedagoška fakulteta 0 0 0