Deficiency of Clusterin Exacerbates High-Fat Diet-Induced Insulin Resistance in Male Mice

Title
Deficiency of Clusterin Exacerbates High-Fat Diet-Induced Insulin Resistance in Male Mice
Author(s)
박소영권민정[권민정]주태진[주태진]허정윤김용운김종연원규장김재룡배영경박인선[박인선]민본홍[민본홍]이인규[이인규]
Keywords
TYPE-2 DIABETES-MELLITUS; APOLIPOPROTEIN-J CLUSTERIN; GASTRIC BYPASS-SURGERY; CORONARY-HEART-DISEASE; OXIDATIVE STRESS; SKELETAL-MUSCLE; CLUSTERIN/APOLIPOPROTEIN-J; PROSTATE-CANCER; MESSENGER-RNA; A-I
Issue Date
201406
Publisher
ENDOCRINE SOC
Citation
ENDOCRINOLOGY, v.155, no.6, pp.2089 - 2101
Abstract
The present study examined the role of clusterin in insulin resistance in high fat-fed wild-type and clusterin knockout (KO) mice. The plasma levels of glucose and C-peptide and islet size were increased in clusterin KO mice after an 8-week high-fat diet. In an ip glucose tolerance test, the area under the curve for glucose was not different, whereas the area under the curve for insulin was higher in clusterin KO mice. In a hyperinsulinemic-euglycemic clamp, the clamp insulin levels were higher in clusterin KO mice after the high-fat diet. After adjusting for the clamp insulin levels, the glucose infusion rate, suppression of hepatic glucose production, and glucose uptake were lower in clusterin KO mice in the high fat-fed group. The plasma levels of clusterin and clusterin mRNA levels in the skeletal muscle and liver were increased by the high-fat diet. The mRNA levels of the antioxidant enzymes were lower, and the mRNA levels of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 1 and cytokines and protein carbonylation were higher in the skeletal muscle and liver in clusterin KO mice after the high-fat diet. Palmitate-induced gene expressions of NOX1 and cytokines were higher in the primary cultured hepatocytes of clusterin KO mice compared with the wild-type mice. Clusterin inhibited the gene expression and reactive oxygen species generation by palmitate in the hepatocytes and C2C12. AKT phosphorylation by insulin was reduced in the hepatocytes of clusterin KO mice. These results suggest that clusterin plays a protective role against high-fat diet-induced insulin resistance through the suppression of oxidative stress and inflammation.
URI
http://hdl.handle.net/YU.REPOSITORY/32078http://dx.doi.org/10.1210/en.2013-1870
ISSN
0013-7227
Appears in Collections:
의과대학 > 생리학교실 > Articles
의과대학 > 영상의학과학교실 > Articles
의과대학 > 내과학교실 > Articles
의과대학 > 생화학.분자생물학교실 > Articles
의과대학 > 병리학교실 > Articles
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