Exercise with calorie restriction improves insulin sensitivity and glycogen synthase activity in obese postmenopausal women with impaired glucose tolerance - PubMed (original) (raw)

Controlled Clinical Trial

. 2012 Jan 1;302(1):E145-52.

doi: 10.1152/ajpendo.00618.2010. Epub 2011 Oct 18.

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Controlled Clinical Trial

Exercise with calorie restriction improves insulin sensitivity and glycogen synthase activity in obese postmenopausal women with impaired glucose tolerance

Alice S Ryan et al. Am J Physiol Endocrinol Metab. 2012.

Abstract

Our objective was to compare the effects of in vivo insulin on skeletal muscle glycogen synthase (GS) activity in normal (NGT) vs. impaired glucose-tolerant (IGT) obese postmenopausal women and to determine whether an increase in insulin activation of GS is associated with an improvement in insulin sensitivity (M) following calorie restriction (CR) and/or aerobic exercise plus calorie restriction (AEX + CR) in women with NGT and IGT. We did a longitudinal, clinical intervention study of CR compared with AEX + CR. Overweight and obese women, 49-76 yr old, completed 6 mo of CR (n = 46) or AEX + CR (n = 50) with Vo(2 max), body composition, and glucose tolerance testing. Hyperinsulinemic euglycemic (80 mU·m(-2)·min(-1)) clamps (n = 73) and skeletal muscle biopsies (before and during clamp) (n = 58) were performed before and after the interventions (n = 50). After 120 min of hyperinsulinemia during the clamp, GS fractional activity and insulin's effect to increase GS fractional activity (insulin - basal) were significantly lower in IGT vs. NGT (P < 0.01) at baseline. GS total activity increased during the clamp in NGT (P < 0.05), but not IGT, at baseline. CR and AEX + CR resulted in a significant 8% weight loss with reductions in total fat mass, visceral fat, subcutaneous fat, and intramuscular fat. Overall, M increased (P < 0.01), and the change in M (postintervention - preintervention) was associated with the change in insulin-stimulated GS fractional activity (partial r = 0.44, P < 0.005). In IGT, the change (postintervention - preintervention) in insulin-stimulated GS total activity was greater following AEX + CR than CR alone (P < 0.05). In IGT, insulin-stimulated GS-independent (P < 0.005) and fractional activity (P = 0.06) increased following AEX + CR. We conclude that the greatest benefits at the whole body and cellular level (insulin activation of GS) in older women at highest risk for diabetes are derived from a lifestyle intervention that includes exercise and diet.

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Figures

Fig. 1.

Fig. 1.

Basal and insulin-stimulated glycogen synthase (GS) activity by glucose tolerance status [normal (NGT) and impaired glucose tolerance (IGT)] within each intervention [calorie restriction (CR) alone, aerobic exercise training (AEX) + CR]. Top: GS-independent (GSI) activity. Middle: GS total (GST) activity. Bottom: GS fractional (GSF) activity. NGT CR, n = 13; IGT CR, n = 6; NGT AEX + CR, n = 20; IGT AEX + CR, n = 11. a_P_ < 0.05; b_P_ < 0.01; c_P_ < 0.005; d_P_ < 0.001; e_P_ < 0.0005; f_P_ < 0.0001. *P = 0.06 by paired Student's _t_-test. Pre, preintervention; post, postintervention.

Fig. 2.

Fig. 2.

Effect of intervention (CR or AEX + CR) on insulin-stimulated GSI (top), GST (middle), and GSF (bottom) activity in women with NGT and IGT. Comparisons were made with ANOVA adjusted for baseline value, intervention, glucose tolerance status and, when appropriate, an intervention × glucose tolerance status, followed by Tukey-Kramer post hoc tests. Sample size as in Fig. 1.

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References

    1. American Diabetes Association Diagnosis and classification of diabetes mellitus. Diabetes Care 32, Suppl 1: S62–S67, 2009 - PMC - PubMed
    1. Bogardus C, Lillioja S, Stone K, Mott D. Correlation between muscle glycogen synthase activity and in vivo insulin action in man. J Clin Invest 73: 1185–1190, 1984 - PMC - PubMed
    1. Bogardus C, Tataranni PA. Reduced early insulin secretion in the etiology of type 2 diabetes mellitus in Pima Indians. Diabetes 51, Suppl 1: S262–S264, 2002 - PubMed
    1. Bryson JM, King SE, Burns CM, Baur LA, Swaraj S, Caterson ID. Changes in glucose and lipid metabolism following weight loss produced by a very low calorie diet in obese subjects. Int J Obes Relat Metab Disord 20: 338–345, 1996 - PubMed
    1. Christ-Roberts CY, Pratipanawatr T, Pratipanawatr W, Berria R, Belfort R, Kashyap S, Mandarino LJ. Exercise training increases glycogen synthase activity and GLUT4 expression but not insulin signaling in overweight nondiabetic and type 2 diabetic subjects. Metabolism 53: 1233–1242, 2004 - PubMed

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