Lipotoxicity in a vicious cycle of pancreatic beta cell exhaustion

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

Povzetek

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.

Ključne besede

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

Podatki

Jezik:	Angleški jezik
Leto izida:	2022
Tipologija:	1.01 - Izvirni znanstveni članek
Organizacija:	UM FNM - Fakulteta za naravoslovje in matematiko
Založnik:	MDPI
UDK:	577.35:616.151
COBISS:	114930947
ISSN:	2227-9059
Št. ogledov:	8
Št. prenosov:	0
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Slovenski jezik
Sekundarne ključne besede:	mitohondrijska disfunkcija;diabetes;izločanje inzulina;proteini;mitohondrijska disfunkcija;sladkorna bolezen;
Vrsta dela (COBISS):	Članek v reviji
Strani:	str. 1-16
Letnik:	ǂVol. ǂ10
Zvezek:	ǂiss. ǂ7
Čas izdaje:	2022
DOI:	10.3390/biomedicines10071627
ID:	23715945