The Effect of Acute Exercise on Undercarboxylated Osteocalcin and Insulin Sensitivity in Obese Men

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.

Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle

“…The ϳ6% impairment in the postexercise enhancement of insulin sensitivity is a small yet statistically significant effect determined via the hyperinsulinemic euglycemic clamp, a technique commonly used as a gold-standard measurement of IS. Although we did not measure resting vs. postexercise IS, it has been shown previously that whole body IS was elevated by 32% 18 h after exercise in sheep (24) and to a similar degree 3 h postexercise in an older overweight population (19). Since exercise is an effective means of improving IS for not only healthy individuals but those with insulin resistance (36), it can be suggested that any impairment to this beneficial effect is clinically relevant.…”

“…Muscle samples were obtained from the middle third of the vastus lateralis muscle using the percutaneous needle biopsy technique (19). After injection of a local anaesthetic into the skin and fascia (1% Xylocaine; Astra Zeneca), a small incision was made and a muscle sample taken (ϳ100 -200 mg) using a Bergström biopsy needle with suction.…”

“…IS was determined using a hyperinsulinemic euglycemic insulin clamp, as described previously (16,19). Briefly, 3 h after the exercise bout, insulin (Actrapid; Novo Nordisk, Bagsvaerd, Denmark) was infused (initial bolus 9 mU/kg and then continuously at 40 mU·m 2 ·min Ϫ1 ) for ϳ120 min, with plasma glucose maintained at ϳ5 mmol/l, using variable infusion rates of 25% vol/vol glucose.…”

Mechanisms for greater insulin-stimulated glucose uptake in normal and insulin-resistant skeletal muscle after acute exercise

“…Insulin-stimulated AS160 phosphorylation (p-AS160) and glucose uptake have been studied in humans after onelegged exercise (86,118 (118). However, high-intensity interval cycle ergometry led to greater glucose disposal during a euglycemic hyperinsulinemic clamp without elevated muscle p-AS160 Thr 642 at 3 h postexercise (72). Greater AS160 phosphorylation has often, but not always, been found after exercise that improved insulin sensitivity.…”

The effect of hyperinsulinaemic-euglycaemic clamp and exercise on bone remodeling markers in obese men

“…11,12 Acute exercise also increases OC and the undercarboxylated form of OC in obese men, and this increase is related to a reduction in serum glucose levels and higher insulin sensitivity as measured by the use of an hyperinsulinaemic-euglycaemic clamp (HEC). 13,14 Using these same patients, we now hypothesise that, (a) at rest, BRMs will be suppressed during a 2 h HEC in obese men, and (b) exercise prior to insulin clamping will increase BRMs and that in turn will prevent the predicted suppression of BRMs in response to the HEC. In the current study, we therefore use the HEC as a tool to deliver and then examine the effects of insulin and glucose on BRMs.…”