title: Down-regulation of zinc transporter 8 in the pancreas of db/db mice is rescued by Exendin-4 administration.
abstract: Recent human genetic studies have revealed that common variants of the zinc transporter 8 (ZnT-8) gene are strongly associated with type 2 diabetes mellitus (T2DM). ZnT-8 has been suggested as a potential candidate in the regulation of insulin secretion in pancreatic β-cells. In this study, we aimed to explore the expression of ZnT-8 in the development of T2DM. The expression of ZnT-8 was investigated in the pancreas and adipose tissue of homozygous db/db mice compared to heterozygous sibling db/+ mice (n=6-8). Furthermore, the effect of Exendin-4 (an analogue of glucagon-like peptide-1) on ZnT-8 expression was examined in the db/db mice. Exendin-4 or vehicle (control) was administered (i.p., 1 nmol/kg) to diabetic 8-week-old db/db mice daily for 14 days (n=8). The results revealed that ZnT-8 protein levels in the pancreas of db/db mice were reduced, accompanied by a decrease in ZnT-8 mRNA. ZnT-8 mRNA and protein levels were also significantly reduced in the epididymal and visceral fat of the db/db mice. Treatment with Exendin-4 up-regulated ZnT-8 gene expression in the pancreas of the db/db mice, but did not affect its expression in adipose tissue. These findings suggest that ZnT-8 synthesis in the pancreas and adipose tissue is down-regulated in db/db mice. Reduced ZnT-8 production in the pancreas may advance defects in insulin secretion in diabetes. These may be reversed, at least partially, by the administration of Exendin-4.
authors: Department of Endocrinology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors: Bao-Ying
authors: BY
authors: Liu
authors: Youzhao
authors: Y
authors: Jiang
authors: Zhongyan
authors: Z
authors: Lu
authors: Shufa
authors: S
authors: Li
authors: Debing
authors: D
authors: Lu
authors: Bing
authors: B
authors: Chen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects; D000077270:Exenatide; D017353:Gene Deletion; D015870:Gene Expression / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D054411:Receptors, Leptin / Q000235:genetics*; D014688:Venoms / Q000008:administration & dosage / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism; D000075703:Zinc Transporter 8
chemical_list: D027682:Cation Transport Proteins; D007004:Hypoglycemic Agents; D010455:Peptides; D054411:Receptors, Leptin; C516348:Slc30a8 protein, mouse; D014688:Venoms; D000075703:Zinc Transporter 8; D000077270:Exenatide; D015032:Zinc