The present study was undertaken to examine the effect of prolonged running on monocyte intracellular cytokine production and plasma cytokine concentration. Blood samples were collected 1 h before, immediately after, 2 h after, and 24 h after a competitive marathon run. There was no change in the number of cells spontaneously producing tumor necrosis factor (TNF)-alpha; however, there was a decrease in the number of cells producing interleukin (IL)-1alpha and IL-6 (P < 0.01) postexercise. In contrast, there was an increase in the number of monocytes that responded to lipopolysaccharide stimulation by producing IL-1alpha, TNF-alpha, and IL-6 (P < 0.01) immediately and 2 h postexercise; however, these cells contained less cytokine (P < 0.05). Plasma IL-6, TNF-alpha, epinephrine, norepinephrine, and cortisol concentrations were markedly increased (P < 0.01) postexercise. These data demonstrate that circulating monocytes are not the source of elevated levels of plasma IL-6 and TNF-alpha after prolonged running. In addition, it is likely that stress hormones result in a decrease in the amount of cytokine produced by LPS-stimulated cells postexercise.

We determined whole-body insulin sensitivity, long-chain fatty acyl coenzyme A (LCACoA) content, skeletal muscle triglyceride (TG(m)) concentration, fatty acid transporter protein content, and oxidative enzyme activity in eight patients with type 2 diabetes (TYPE 2); six healthy control subjects matched for age (OLD), body mass index, percentage of body fat, and maximum pulmonary O(2) uptake; nine well-trained athletes (TRAINED); and four age-matched controls (YOUNG). Muscle biopsies from the vastus lateralis were taken before and after a 2-h euglycemic-hyperinsulinemic clamp. Oxidative enzyme activities, fatty acid transporters (FAT/CD36 and FABPpm), and TG(m) were measured from basal muscle samples, and total LCACoA content was determined before and after insulin stimulation. Whole-body insulin-stimulated glucose uptake was lower in TYPE 2 (P < 0.05) than in OLD, YOUNG, and TRAINED. TG(m) was elevated in TYPE 2 compared with all other groups (P < 0.05). However, both basal and insulin-stimulated skeletal muscle LCACoA content were similar. Basal citrate synthase activity was higher in TRAINED (P < 0.01), whereas beta-hydroxyacyl CoA dehydrogenase activity was higher in TRAINED compared with TYPE 2 and OLD. There was a significant relationship between the oxidative capacity of skeletal muscle and insulin sensitivity (citrate synthase, r = 0.71, P < 0.001; beta-hydroxyacyl CoA dehydrogenase, r = 0.61, P = 0.001). No differences were found in FAT/CD36 protein content between groups. In contrast, FABPpm protein was lower in OLD compared with TYPE 2 and YOUNG (P < 0.05). In conclusion, despite markedly elevated skeletal muscle TG(m) in type 2 diabetic patients and strikingly different levels of whole-body glucose disposal, both basal and insulin-stimulated LCACoA content were similar across groups. Furthermore, skeletal muscle oxidative capacity was a better predictor of insulin sensitivity than either TG(m) concentration or long-chain fatty acyl CoA content.

These data show that the increased circulating IL-6 concentrations seen in patients with Type 2 diabetes are strongly related to fat mass and not insulin responsiveness, and suggest that neither IL-6 nor TNFalpha are indicative of insulin resistance.

No abstract

Acute exercise improves insulin sensitivity for hours after the exercise is ceased. The skeleton contributes to glucose metabolism and insulin sensitivity via osteocalcin (OC) in its undercarboxylated (ucOC) form in mice. We tested the hypothesis that insulin sensitivity over the hours after exercise is associated with circulating levels of ucOC. Eleven middle-aged (58.1 AE 2.2 years mean AE SEM), obese (body mass index [BMI] ¼ 33.1 AE 1.4 kg/m 2 ) nondiabetic men completed a euglycemic-hyperinsulinemic clamp at rest (rest-control) and at 60 minutes after exercise (4 Â 4 minutes of cycling at 95% of HR peak ). Insulin sensitivity was determined by glucose infusion rate relative to body mass (GIR, mL/kg/min) as well as GIR per unit of insulin (M-value). Blood samples and five muscle biopsies were obtained; two at the resting-control session, one before and one after clamping, and three in the exercise session, at rest, 60 minutes after exercise, and after the clamp. Exercise increased serum ucOC (6.4 AE 2.1%, p ¼ 0.013) but not total OC (p > 0.05). Blood glucose was $6% lower and insulin sensitivity was $35% higher after exercise compared with control (both p < 0.05). Phosphorylated (P)-AKT (Ak thymoma) was higher after exercise and insulin compared with exercise alone (no insulin) and insulin alone (no exercise, all p < 0.05). In a multiple-linear regression including BMI, age, and aerobic fitness, ucOC was associated with whole-body insulin sensitivity at rest (b ¼ 0.59, p ¼ 0.023) and after exercise (b ¼ 0.66, p ¼ 0.005). Insulin sensitivity, after acute exercise, is associated with circulating levels of ucOC in obese men. Whether ucOC has a direct effect on skeletal muscle insulin sensitivity after exercise is yet to be determined.