Vladimir Grubelnik (Author), Jan Zmazek (Author), Matej Završnik (Author), Marko Marhl (Author)

Abstract

Hyperlipidemia is a common metabolic disorder in modern society and may precede hyperglycemia and diabetes by several years. Exactly how disorders of lipid and glucose metabolism are related is still a mystery in many respects. We analyze the effects of hyperlipidemia, particularly free fatty acids, on pancreatic beta cells and insulin secretion. We have developed a computational model to quantitatively estimate the effects of specific metabolic pathways on insulin secretion and to assess the effects of short- and long-term exposure of beta cells to elevated concentrations of free fatty acids. We show that the major trigger for insulin secretion is the anaplerotic pathway via the phosphoenolpyruvate cycle, which is affected by free fatty acids via uncoupling protein 2 and proton leak and is particularly destructive in long-term chronic exposure to free fatty acids, leading to increased insulin secretion at low blood glucose and inadequate insulin secretion at high blood glucose. This results in beta cells remaining highly active in the “resting” state at low glucose and being unable to respond to anaplerotic signals at high pyruvate levels, as is the case with high blood glucose. The observed fatty-acid-induced disruption of anaplerotic pathways makes sense in the context of the physiological role of insulin as one of the major anabolic hormones.

Keywords

mitohondrijska disfunkcija;diabetes;izločanje inzulina;proteini;sladkorna bolezen;ne zaključna dela;insulin secretion;lipids;PEP cycle;uncoupling proteins;mitochondrial dysfunction;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UM FNM - Faculty of Natural Sciences and Mathematics
Publisher: MDPI
UDC: 577.35:616.151
COBISS: 114930947 Link will open in a new window
ISSN: 2227-9059
Views: 8
Downloads: 0
Average score: 0 (0 votes)
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Other data

Secondary language: Slovenian
Secondary keywords: mitohondrijska disfunkcija;diabetes;izločanje inzulina;proteini;mitohondrijska disfunkcija;sladkorna bolezen;
Type (COBISS): Article
Pages: str. 1-16
Volume: ǂVol. ǂ10
Issue: ǂiss. ǂ7
Chronology: 2022
DOI: 10.3390/biomedicines10071627
ID: 23715945