Regulation and functional effects of ZNT8 in human pancreatic islets

被引：27
作者：
Lefebvre, Bruno [1 ,2 ]
Vandewalle, Brigitte [1 ,2 ]
Balavoine, Anne-Sophie [1 ,2 ]
Queniat, Gurvan [1 ,2 ]
Moerman, Ericka [1 ,2 ]
Vantyghem, Marie-Christine [1 ,2 ]
Le Bacquer, Olivier [1 ,2 ]
Gmyr, Valery [1 ,2 ]
Pawlowski, Valerie [1 ,2 ]
Kerr-Conte, Julie [1 ,2 ]
Pattou, Francois [1 ,2 ,3 ]
机构：
[1] Univ Lille Nord France, F-59000 Lille, France
[2] UMR859, F-59000 Lille, France
[3] CHU Lille, Dept Endocrine Surg, F-59000 Lille, France
来源：
JOURNAL OF ENDOCRINOLOGY | 2012年 / 214卷 / 02期
关键词：
ZINC TRANSPORTER ZNT8; GENOME-WIDE ASSOCIATION; INDUCED INSULIN-RELEASE; BETA-CELLS; DOWN-REGULATION; GLUCOSE-HOMEOSTASIS; GRAFT-SURVIVAL; DIABETIC MICE; DIETARY ZINC; ALPHA-CELLS;
D O I：
10.1530/JOE-12-0071
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Zinc ions are essential for the formation of insulin crystals in pancreatic beta cells, thereby contributing to packaging efficiency of stored insulin. Zinc fluxes are regulated through the SLC30A (zinc transporter, ZNT) family. Here, we investigated the effect of metabolic stress associated with the prediabetic state (zinc depletion, glucotoxicity, and lipotoxicity) on ZNT expression and human pancreatic islet function. Both zinc depletion and lipotoxicity (but not glucotoxicity) downregulated ZNT8 (SLC30A8) expression and altered the glucose-stimulated insulin secretion index (GSIS). ZNT8 overexpression in human islets protected them from the decrease in GSIS induced by tetrakis-(2-pyridylmethyl) ethylenediamine and palmitate but not from cell death. In addition, zinc supplementation decreased palmitate-induced human islet cell death without restoring GSIS. Altogether, we showed that ZNT8 expression responds to variation in zinc and lipid levels in human beta cells, with repercussions on insulin secretion. Prospects for increasing ZNT8 expression and/or activity may prove beneficial in type 2 diabetes in humans. Journal of Endocrinology (2012) 214, 225-232
引用
收藏
页码：225 / 232
页数：8
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