Oxidative stress and the etiology of insulin resistance and type 2 diabetes

Abstract

The condition of oxidative stress arises when oxidant production exceeds antioxidant activity in cells and plasma. The overabundance of oxidants is mechanistically connected with the multifactorial etiology of insulin resistance, primarily in skeletal muscle tissue, and the subsequent development of type 2 diabetes. Two important mechanisms for this oxidant excess are 1) the mitochondrial overproduction of hydrogen peroxide and superoxide ion in conditions of energy surplus and 2) the enhanced activation of cellular NADPH oxidase via angiotensin II (AT1) receptors. Several recent studies are reviewed that support the concept that direct exposure of mammalian skeletal muscle to an oxidant stress (including hydrogen peroxide) results in stimulation of the serine kinase p38 mitogen-activated protein kinase (p38 MAPK), and that the engagement of this stress-activated p38 MAPK signaling is mechanistically associated with diminished insulin-dependent stimulation of insulin signaling elements and glucose transport activity. The beneficial interactions between the antioxidant α-lipoic acid and the advanced glycation end product inhibitor pyridoxamine to ameliorate oxidant stress-associated defects in whole-body and skeletal muscle insulin action in the obese Zucker rat, a model of pre-diabetes, are also addressed. Overall, this review highlights the importance of oxidative stress in the development of insulin resistance in mammalian skeletal muscle tissue, at least in part via a p38 MAPK-dependent mechanism, and indicates that interventions that reduce this oxidative stress and oxidative damage can improve insulin action in insulin-resistant animal models. Strategies to prevent and ameliorate oxidative stress remain important in the overall treatment of insulin resistance and type 2 diabetes.

In vitro inhibition activity of polyphenol-rich extracts from Syzygium aromaticum (L.) Merr. & Perry (Clove) buds against carbohydrate hydrolyzing enzymes linked to type 2 diabetes and Fe2+-induced lipid peroxidation in rat pancreas

“…About 10 g of the ground leaves was extracted with 80% acetone (1:5, v/v) and filtered (filter paper Whatman no. 2) under vacuum. The filtrate was then evaporated using a rotary evaporator under vacuum at 45 °C until about 90% of the filtrate had been evaporated.…”

“…The DPPH free radical scavenging ability was subsequently calculated with respect to the reference, which contained all the reagents without the test sample. The DPPH radical scavenging ability was calculated using the following formula: DPPH radical scavenging ability (%) = (Abs ref -Abs sam )/Abs ref 暳100% (2) where, Abs ref represents absorbance of reference, while Abs sam represents absorbance of sample.…”

“…This results in disturbances in carbohydrate, fat and protein metabolism. Oxidative stress is known to play a significant role in the development and progression of DM [2] . Excessive generation of free radicals and depleted levels of free radical scavenging enzymes have been demonstrated in animal models of diabetes [3,4] .…”

“…Free radicals are formed disproportionately in diabetes by glucose oxidation, nonenzymatic glycation of proteins, and the subsequent oxidative degradation of glycated proteins. Abnormally high levels of free radicals and the simultaneous decline of antioxidant defense mechanisms can lead to damage of cellular organelles and enzymes and also increase lipid peroxidation and beta-cell apoptotic pathways activation [2,5] .…”

Branched‐chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation

“…Chronic low‐grade inflammation16, 17 and oxidative stress18, 19 are major pathophysiological mechanisms involved in T2DM, obesity and atherosclerosis leading to insulin resistance, endothelial dysfunction and micro‐ and macro‐vascular complications. Increased reactive oxygen species (ROS) generation induces endothelial dysfunction by impairing the bioactivity of endothelial NO and promotes leucocyte adhesion, inflammation, thrombosis and smooth muscle cell proliferation—all processes that exacerbate atherosclerosis.…”