Inflammation and nitric oxide production in skeletal muscle of type 2 diabetic patients

Abstract

An inflammatory process may be involved in nitric oxide production in skeletal muscle of type 2 diabetic patients. Nitric oxide generation in skeletal muscle was assessed in 14 non-complicated type 2 diabetic patients and in 12 healthy subjects. In samples of quadriceps femoris muscle, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), nitrite, nitrate and nitrotyrosine were determined. The macrophage-specific antigen CD163, the T-cell membrane factor CD154 and tumour necrosis factor-alpha (TNF-alpha) were also assayed. In six patients, ultrastructural analysis of muscle was performed. Nitrites and nitrates were increased in patients as compared to controls (22.7+/-4.5 and 32.7+/-7.0 vs 16.0+/-2.9 and 22.8+/-4.0 micromol/mg protein; P<0.001, Mann-Whitney U test). Endothelial NOS was similar in diabetic and control subjects (36.4+/-13.8 vs 36.3+/-6.8 ng/mg protein), contrasting with the significant increase of iNOS recorded in patients (34.3+/-13.0 vs 8.5+/-2.8 ng/mg protein, P<0.00002). Nitrotyrosine levels were higher in the patient than in the control group (42.1+/-24.4 vs 10.3+/-2.5 ng/mg protein, P<0.00002), as were CD163 (10-fold) and TNF-alpha (fourfold) levels. Furthermore, CD154 levels were detectable only in the patient samples (10.2+/-5.3 ng/mg protein). By multiple-regression analysis, changes in glycated haemoglobin values could predict 96% variation in nitrotyrosine. Macrophages were present in all muscle samples analysed by electromicroscopy. The increased levels of CD163, CD154 and TNF-alpha indicate that an inflammatory process occurs in skeletal muscle of type 2 diabetic patients. This may contribute to iNOS induction, muscle damage and insulin resistance.

Skeletal muscle inflammation and nitric oxide in patients with COPD

“…Several studies have reported increased inflammatory markers in the skeletal muscle of patients with different conditions including COPD [6,7,[20][21][22][23]. The results of the present study expand this observation by evaluating several inflammatory nucleus of muscle fibre; C: capillary; NE: nucleus of capillary endothelial cell; P:…”

Nitric oxide inhibits insulin-degrading enzyme activity and function through S-nitrosylation

“…Published by Elsevier Inc. measurement of NO production) are increased in patients with T2DM relative to healthy individuals [1,4]. The actions of NO can be classified as cGMP-dependent actions (such as those related to vascular dilation) or as reactive nitrogen species-mediated (independent of the actions of cGMP).…”

“…The cGMP-independent effects are often mediated by nitrosative posttranslational modifications, such as S-nitrosylation, and are thought to play a role in pathological responses, including insulin resistance [5]. Snitrosylation involves the covalent attachment of a NO moiety to protein sulfhydryls and is increased in the skeletal muscle of patients with T2DM [4]. Insulin signaling molecules, such as the insulin receptor, insulin receptor substrate-1 and Akt/PKB, are S-nitrosylated in the skeletal muscle of obese, diabetic mice [6].…”

Liver Function Status in Male Wister Rats Treated with Ethanol Extract of the Leaves of Nauclea latifolia Owing to Aluminum Chloride-Induced Oxidative Stress

“…Thiobarbituric acid reactive substances (TBARS): Hepatic lipid peroxidation was determined as thiobarbituric acid reactive substances as described by Torres et al [6]. Lipid peroxidation generates peroxide intermediates which upon cleavage release malondialdehyde, a product which react with thiobarbituric acid.…”