title: Skeletal muscle interleukin-6 and tumor necrosis factor-alpha release in healthy subjects and patients with type 2 diabetes at rest and during exercise.
abstract: To examine the influence of type 2 diabetes on cytokine release from the leg at rest and during exercise, 9 male type 2 diabetics (D) and 8 age-, gender-, Vo2peak-, weight- and body mass index (BMI)-matched control subjects (C) were studied before and after 25 minutes of supine bicycle exercise at 60% Vo2peak. Blood samples were obtained from a femoral artery and vein from 1 limb, and plasma was analyzed for glucose and the cytokines, interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. Leg blood flow (LBF) was measured by thermodilution in the femoral vein, and net leg IL-6, TNF-alpha, and glucose balance were calculated as the product of LBF and femoral arteriovenous (fa-v) glucose, IL-6, and TNF-alpha difference. Arterial plasma glucose and IL-6 were higher (P<.05) at rest in D compared with C, but there were no differences in arterial TNF-alpha concentrations at rest when comparing groups. Despite measurable arterial levels of both IL-6 and TNF-alpha in both groups at rest, there was not net leg release of either cytokine at rest. Exercise increased (P<.05) IL-6 release and glucose uptake in both D and C, and contracting leg glucose uptake was similar when comparing D with C. While not significant, there was a trend (P=.1) for augmented exercise-induced IL-6 release in D compared with C. In contrast, exercise did not result in TNF-alpha release in either D or C. These data demonstrate that basal circulating TNF-alpha is not elevated in patients with type 2 diabetes when matched for BMI with control subjects. The results also suggest that neither type 2 diabetic nor healthy skeletal muscle releases these cytokines at rest, indicating that organs other than skeletal muscle contribute to the elevated basal IL-6 in type 2 diabetics. In contrast with IL-6, exercise does not result in the release of TNF-alpha from the contracting limbs of either healthy subjects or patients with type 2 diabetes.
authors.affiliation: Skeletal Muscle Research Laboratory, School of Medical Sciences, RMIT University, Bundoora, Victoria, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Febbraio
authors.forename: Adam
authors.initials: A
authors.lastname: Steensberg
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Starkie
authors.forename: Glenn K
authors.initials: GK
authors.lastname: McConell
authors.forename: Bronwyn A
authors.initials: BA
authors.lastname: Kingwell
mesh_terms: D000328:Adult; D001642:Bicycling; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D015444:Exercise; D005260:Female; D005263:Femoral Artery; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism*; D007866:Leg; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D010101:Oxygen Consumption; D012146:Rest; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha