Reduction Levels and the Effects of High-Molecular-Weight Adiponectin via AMPK/eNOS in Chinese Type 2 Diabetes

Abstract

This study was to investigate the change of high-molecula-weight (HMW) adiponectin (APN) isoform, the association between type 2 diabetes mellitus (T2DM) and HMW APN isoform, the variation of Disulfide-bond A oxidoreductase-like protein (DsbA-L), the effect of HMW APN isoform on AMP-dependent protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) in Chinese T2DM. 169 patients aged at (48.7±9.4) years and 107 healthy control subjects aged at (42.6±7.8) years took part in this study. Anthropometric measures of the characters were assayed and different APN isoforms, DsbA-L, AMPK and eNOS levels were determined. Ln(sRAGE) and Ln(Adiponectin) were significantly lower and significantly higher for the other characteristics in T2DM. Ln(Adiponectin) was negatively and significantly correlated with WHR, Ln(triglycerides), fasting plasma glucose, HbA1c (%) in control subjects and T2DM patients. Plasma and adipose tissue total APN and HMW APN were significantly reduced in newly diagnosed T2DM patients. DsbA-L was markedly down-regulated in diabetic adipose tissue. HMW APN caused significant decreases in AMPK and eNOS phosphorylation levels of human umbilical vein endothelial cells (HUVECs). Our results demonstrated that total APN levels was closely related to the risk of T2DM and HMW APN reduction was involved in the diabetic vascular AMPK/eNOS signal pathway. The findings will provide insight into novel therapeutic approaches for reducing the elevated cardiovascular risk associated with T2DM.

Potential Protective Function of Adiponectin in Diabetic Retinopathy

“…It regulates glucolipid and energy metabolism via adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) [ 12 ]. Extensive research has been conducted on the relationship between plasma APN levels and various metabolic diseases, such as type 2 diabetes mellitus (T2DM) [ 13 , 14 ], atherosclerosis, inflammation, obesity, insulin resistance [ 15 ], cardiovascular disease [ 16 , 17 ], and many others. Few studies, however, have concentrated on the causes of the association between plasma APN levels and DR, the impact of APN on DR, and the role APN plays in the pathogenesis of DR.…”

Ginsenoside CK ameliorates hepatic lipid accumulation via activating the LKB1/AMPK pathway in vitro and in vivo

“…41,42 AMPK acts as a key sensor in maintaining energy homeostasis and is an important regulator of lipid and glucose metabolism, and thus, is considered as a potential target for the treatment of T2DM, obesity, and other related metabolic diseases. 43 AMPK exists as a heterotrimer complex containing an α subunit with catalytic activity and β and γ subunits in charge of regulation. The complex could be modified and activated by a phosphorylated substrate at residue Thr 172 of the α subunit when combined with AMP at the γ subunit.…”

Association of blood endothelial dysfunction markers with type 2 diabetes mellitus complications

“…NO Також у наших дослідженнях визначено, що у міру збільшення тяжкості ЦД2 гальмувалась експресія eNOS та прогресивно знижувався її рівень в крові, що відповідає даним [21]. Зниження вмісту eNOS можна розглядати як біомаркер оксидантного стресу [22].…”