Abstract
The purpose is to determine the effects of 6 months caloric restriction and aerobic training (3x/wk) (CR+AEX) on c-CBL associated protein (CAP) gene expression in women with a history of GDM. CAP is involved in cell signaling and protein ubiquitination, and is linked to the development of insulin resistance. Obese (BMI=32 ± 1 kg/m2, % fat=46 ± 2, X ± SEM), sedentary (VO2 max=21.2 ± 1.2 ml/kg/min), women aged 52 ± 2 years participated in 6 months D+WL (n=10) with body composition, fitness (VO2 max), and glucose tolerance testing. Insulin sensitivity was assessed during the last 30 min of 2-hour hyperinsulinemic-euglycemic clamps (40 mU.m-2.min-1) pre and post interventions. Vastus lateralis skeletal muscle biopsies (n=7) were conducted and CAP, GLUT4 and glycogen synthase (GS) gene expression measured by RT-PCR. No change in FFM by DXA was observed, but body weight decreased 8% with losses of total body fat mass (P<0.05) and a 10% increase in VO2 max (P<0.01). Glucose and insulin areas under the curve by OGTT decreased (P<0.05). Glucose utilization during the clamp increased 27% (23.1 ± 3.8 vs. 29.4 ± 3.6 umol.kg.min-1, P<0.05). Vastus lateralis skeletal muscle CAP expression increased 21% (P<0.05) but GLUT4 did not. Results suggest that changes in CAP could be involved in the improvement in glucose metabolism with caloric restriction and aerobic training in women with a history of gestational diabetes.
Highlights
Women with a previous diagnosis of gestational diabetes mellitus (GDM) have defects in insulin secretion and action [1,2,3,4,5]; placing these women at elevated risk for obesity and the development of type 2 diabetes mellitus (T2DM) [6,7,8,9,10]
Our prior data indicate that considerable insulin resistance is present in older overweight and sedentary women with a previous diagnosis of GDM [21] and that six-months of caloric restriction and aerobic exercise reduces body weight, abdominal fat, and improves insulin sensitivity in older women with previously diagnosed GDM [13]
We demonstrate that increased skeletal muscle cbl associated protein (CAP) and glycogen synthase (GS) expression following CR+AEX may be a potential mechanism for these observed improvements in glucose metabolism
Summary
Women with a previous diagnosis of gestational diabetes mellitus (GDM) have defects in insulin secretion and action [1,2,3,4,5]; placing these women at elevated risk for obesity and the development of type 2 diabetes mellitus (T2DM) [6,7,8,9,10]. Does increased postpartum physical activity in women with previous GDM halve subsequent risk of developing T2DM [11], modest weight loss within the first year post-partum is associated with. The intent of this study is to build upon our previous work that a diet with and without aerobic exercise reduces body weight and visceral and subcutaneous abdominal fat and improves insulin sensitivity in women with a previous diagnosis of GDM [13], by examining a potential mechanism for this improvement in glucose homeostasis. In animal models, it appears that modification of diet and physical activity can influence CAP, with associated improvements in insulin sensitivity [15]. We hypothesized that in middle-aged and older women who had a previous diagnosis of GDM, caloric restriction and exercise would upregulate skeletal muscle CAP gene expression and improve insulin sensitivity
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