title: A hypothetical model to solve the controversy over the involvement of UCP2 in palmitate-induced β-cell dysfunction.
abstract: The aim of this article is to solve an existing controversy over the involvement of uncoupling protein-2 in the impairment of glucose-stimulated insulin secretion induced by chronic exposure of β-cells to palmitate. We analyzed and compared the results of studies that support and that deny the involvement of uncoupling protein-2 in this impairment. We observed that this impairment could occur in multiple stages. We provide a model in which palmitate-induced impairment of glucose-stimulated insulin secretion is proposed to occur in two stages, early stage and late stage, depending on the integrity of electron supply (glycolysis and Krebs cycle) and transport system through electron transport chain after palmitate treatment. Prolonged exposure of β-cells to palmitate can impair this system. Early-stage impairment occurs due to uncoupling by uncoupling protein-2 when this system is still intact. When this system becomes impaired, late-stage impairment occurs mainly due to reduced glucose-stimulated adenosine triphosphate production independent of uncoupling by uncoupling protein-2. The change in glucose-stimulated oxygen uptake after palmitate treatment reflects the integrity of this system and can be used to differentiate between the two stages. Some β-cells lines and islets appear to be more resistant to palmitate-induced impairment of electron supply and transport system than others, and therefore early stage is prominent in the more resistant cell lines and less prominent or absent in the less resistant cell lines. This may help to resolve the pathogenesis of diabetes and to monitor the progression of palmitate-induced β-cell dysfunction.
authors.affiliation: Kafr El-Sharakwa Medical Center, Kafr El-Sharakwa, Aga, Dakahlia, Egypt. alaa-shaheen@outlook.com.
authors.forename: Alaa
authors.initials: A
authors.lastname: Shaheen
authors.affiliation: Department of Zoology, Faculty of Science, Omar Al Mukhtar University, Bayda, Libya.
authors.forename: Ahmad M A
authors.initials: AM
authors.lastname: Aljebali
mesh_terms: D000818:Animals; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008962:Models, Theoretical; D019308:Palmitic Acid / Q000494:pharmacology*; D000071246:Uncoupling Protein 2 / Q000378:metabolism*
chemical_list: D007328:Insulin; D000071246:Uncoupling Protein 2; D019308:Palmitic Acid
keywords: Electron transport chain; Glucose-stimulated insulin secretion; Oxygen uptake; Palmitate; Uncoupling protein-2; β-cells