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Involvement of senescence marker protein‐30 in glucose metabolism disorder and non‐alcoholic fatty liver disease
Author(s) -
Kondo Yoshitaka,
Ishigami Akihito
Publication year - 2016
Publication title -
geriatrics and gerontology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 57
eISSN - 1447-0594
pISSN - 1444-1586
DOI - 10.1111/ggi.12722
Subject(s) - endocrinology , steatohepatitis , medicine , oxidative stress , fatty liver , glucose metabolism disorder , insulin , insulin resistance , disease
Senescence marker protein‐30 ( SMP 30) was found to decrease in the liver, kidneys and lungs of mice during aging. SMP 30 is a pleiotropic protein that acts to protect cells from apoptosis by enhancing plasma membrane Ca 2+ ‐pump activity and is bona fide gluconolactonase ( EC 3.1.1.17) that participates in the penultimate step of the vitamin C biosynthetic pathway. For the past several years, we have obtained strong evidence showing the close relationship between SMP 30, glucose metabolism disorder and non‐alchoholic fatty liver disease in experiments with SMP 30 knockout mice. Emerging proof links the following abnormalities: (i) the reduction of SMP 30 by aging and/or excessive dietary fat or genetic deficiency causes a loss of Ca 2+ pumping activity, which impairs acute insulin release in pancreatic β‐cells, initiates inflammatory responses with oxidative stress and endoplasmic reticulum stress in non‐alchoholic steatohepatitis, exacerbates renal tubule damage, and introduces tubulointerstitial inflammation and fibrosis in diabetic nephropathy; (ii) vitamin C insufficiency also impairs acute insulin secretion in pancreatic β‐cells by a mechanism distinct from that of the SMP 30 deficiency; and (iii) the increased oxidative stress by concomitant deficiencies of SMP 30, superoxide dismutase 1 and vitamin C similarly causes hepatic steatosis. Here, we review recent advances in our understanding of SMP 30 in glucose metabolism disorder and non‐alchoholic fatty liver disease. G eriatr G erontol I nt 2016; 16 (Suppl. 1): 4–16.