Suppressor of Cytokine Signaling 3 Expression and Insulin Resistance in Skeletal Muscle of Obese and Type 2 Diabetic Patients

Abstract

Interleukin-6 (IL-6) could be a possible mediator of insulin resistance. We investigated whether IL-6 could inhibit insulin signaling in human skeletal myotubes and whether suppressor of cytokine signaling 3 (SOCS-3) could be related to insulin resistance in vivo in humans. IL-6 inhibited insulin signaling and induced SOCS-3 expression in differentiated myotubes. SOCS-3 mRNA levels were significantly increased in the skeletal muscle of type 2 diabetic patients compared with control subjects and correlated with reduced insulin-stimulated glucose uptake. In contrast, SOCS-3 mRNA levels were reduced in muscle of obese nondiabetic subjects compared with type 2 diabetic patients, despite similar circulating concentrations of IL-6. Increased SOCS-3 mRNA levels in diabetes were not attributable to hyperglycemia, as type 1 diabetic patients had normal SOCS-3 mRNA expression in muscle. However, the combination of high glucose and IL-6 levels in type 2 diabetic patients may induce SOCS-3 expression, as has been seen in human muscle cells. In subcutaneous adipose tissue, SOCS-3 mRNA levels were increased in obese individuals and strongly correlated with IL-6 expression, supporting a paracrine effect of IL-6 on SOCS-3 expression in fat. Taken together, our results showed that SOCS-3 expression in human skeletal muscle in vivo is not related to insulin resistance in the presence of elevated IL-6 concentrations and suggest that cytokine action could differ in type 2 diabetic patients and nondiabetic obese subjects. Diabetes 53

Activation of liver X receptors promotes lipid accumulation but does not alter insulin action in human skeletal muscle cells

“…The patients with type 2 diabetes were treated with oral hypoglycaemic agents (metformin and sulfonylurea). [23][24][25][26], the rates of myoblasts' growth and fusion into myotubes were similar, and there was no apparent morphological difference, among cultured skeletal muscle cells from control subjects and patients with type 2 diabetes.…”

“…Proteins (40 μg) were separated by SDS-PAGE. After transfer, phosphorylated protein kinase B (PKB) was detected using an antiphospho-Ser 473 antibody (Upstate Biotechnology, Lake Placid, NY, USA) as previously described [24]. To normalise for equal protein amount, the blots were stripped and probed again with anti-PKB antibody (Upstate Biotechnology).…”

Soluble CD163: a biomarker linking macrophages and insulin resistance

“…Furthermore, recent studies have shown that adipose tissue in obese individuals is inflamed and infiltrated by macrophages that secrete proinflammatory cytokines such as TNF-α and IL-6 [3]. These cytokines promote insulin resistance and are thought to be directly involved in the development of obesity-related disease [4][5][6].…”

Discordant gene expression in skeletal muscle and adipose tissue of patients with type 2 diabetes: effect of interleukin-6 infusion

“…On the other hand, muscle contraction can initiate gene transcription within the cell as a result of factors such as elevated cytosolic calcium levels, factors that would have no effect on adipocyte gene transcription [8] and that lead to discordant gene expression when comparing the two tissue types. Indeed, in a recent study, mRNA gene expression of suppressor of cytokine signalling (SOCS) 3 was found to be discordantly regulated; it was reduced in skeletal muscle but increased in adipose tissue when comparing obese with lean subjects [9]. Since therapeutics for insulin resistance are now being developed in a tissue-specific manner [10], it is important to compare metabolic gene expression in insulin-sensitive tissue from patients with type 2 diabetes.…”