title: Interleukin-22 restored mitochondrial damage and impaired glucose-stimulated insulin secretion through down-regulation of uncoupling protein-2 in INS-1 cells.
abstract: Defective glucose-stimulated insulin secretion (GSIS) induced by chronic exposure to fatty acids is a hallmark of type 2 diabetes (T2D). Interleukin-22 (IL-22) has been shown to exert beneficial effects on insulin secretion and to protect pancreatic β-cells from stress. Moreover, uncoupling protein-2 (UCP-2) plays a central role in the regulation of GSIS and β-cell dysfunction, whereas the role of UCP-2 in IL-22-enhanced glycemic control under conditions of lipotoxicity remains unclear. In this present study, we investigated the effects of IL-22 on rat insulin-secreting cells (INS-1 cells) and the mechanisms that underlie IL-22 and lipotoxicity-impaired GSIS in vitro. Chronic palmitate (PA) treatment impaired insulin secretion and activated UCP-2 expression in INS-1 cells. Furthermore, in INS-1 cells, both reduced mitochondrial membrane potential (ΔΨm) and impaired GSIS induced by PA treatment were effectively reversed by an inhibitor of UCP-2 (genipin). Additionally, compared with the PA-treated group, INS-1 cells treated with IL-22 down-regulated UCP-2 expression, increased mitochondrial membrane potential, and restored GSIS. Together, our findings indicate that chronic exposure to PA could activate UCP-2, resulting in mitochondrial damage and impaired GSIS in INS-1 cells. We also suggest that IL-22 plays a protective role in this process via the down-regulation of UCP-2.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou 510080, China.
authors.forename: Minling
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Nutrition, Guangzhou First People's Hospital, Guangzhou Medical University, 602 Ren Min Bei Road, Guangzhou 510180, P.R. China.
authors.forename: Hanxiao
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, S253 Industry Boulevard, Guangzhou 510282, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, S253 Industry Boulevard, Guangzhou 510282, China.
authors.forename: Yanzhen
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, S253 Industry Boulevard, Guangzhou 510282, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D051381:Rats; D000071246:Uncoupling Protein 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D005947:Glucose; D007328:Insulin; D007378:Interleukins; D000071246:Uncoupling Protein 2; D000097043:Interleukin-22
keywords: glucose-stimulated insulin secretion; interleukin-22; mitochondrial membrane potential; palmitate; uncoupling protein-2