Journal Article

Altered Response of Skeletal Muscle to IL-6 in Type 2 Diabetic Patients

Jiang, Lake Q., Duque-Guimaraes, Daniella E., Krook, Anna, Zierath, Juleen R., Machado, Ubiratan F.

2013

Overview

Interleukin-6 (IL-6) has a dual role in modulating insulin sensitivity, with evidence for this cytokine as both an enhancer and inhibitor of insulin action. We determined the effect of IL-6 exposure on glucose and lipid metabolism in cultured myotubes established from people with normal glucose tolerance or type 2 diabetes. Acute IL-6 exposure increased glycogen synthesis, glucose uptake, and signal transducer and activator of transcription 3 (STAT3) phosphorylation in cultured myotubes from normal glucose tolerant subjects. However, in type 2 diabetic patients, IL-6 was without effect on glucose metabolism and STAT3 signaling, concomitant with increased suppressor of cytokine signaling 3 (SOCS3) expression. IL-6 increased fatty acid oxidation in myotubes from type 2 diabetic and normal glucose tolerant subjects. Expression of IL-6, IL-6 receptor (IL-6R), or glycoprotein 130, as well as IL-6 secretion, was unaltered between cultured myotubes from normal glucose tolerant or type 2 diabetic subjects. Circulating serum IL-6 concentration was unaltered between normal glucose tolerant and type 2 diabetic subjects. In summary, skeletal muscle cells from type 2 diabetic patients display selective IL-6 resistance for glucose rather than lipid metabolism. In conclusion, IL-6 appears to play a differential role in regulating metabolism in type 2 diabetic patients compared with normal glucose tolerant subjects.

• Publisher: American Diabetes Association
• Subject: Animals / Biological and medical sciences / Biopsy / Body fat / Cells, Cultured / Cytokines / Diabetes / Diabetes Mellitus, Type 2 - metabolism / Diabetes. Impaired glucose tolerance / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Etiopathogenesis. Screening. Investigations. Target tissue resistance / Fatty Acids - metabolism / Female / Fundamental and applied biological sciences. Psychology / Glucose / Glucose - metabolism / Glycogen - biosynthesis / Glycoproteins / Glycoproteins - biosynthesis / Health aspects / Humans / Insulin resistance / Insulin Resistance - physiology / Interleukin-6 / Interleukin-6 - analysis / Interleukin-6 - pharmacology / Interleukin-6 - physiology / Kinases / Lipids / Male / Medical sciences / Metabolism / Mice / Mice, Inbred C57BL / Middle Aged / Muscle Fibers, Skeletal - drug effects / Muscle, Skeletal - drug effects / Muscle, Skeletal - metabolism / Muscles / Musculoskeletal system / Oxidation / Phosphorylation / Proteins / Receptors, Interleukin-6 - metabolism / Skeletal muscle / STAT3 Transcription Factor - metabolism / Striated muscle. Tendons / Suppressor of Cytokine Signaling 3 Protein / Suppressor of Cytokine Signaling Proteins - biosynthesis / Type 2 diabetes / Vertebrates: osteoarticular system, musculoskeletal system