Article

Improved pancreatic beta-cell function in type 2 diabetic patients after lifestyle-induced weight loss is related to glucose-dependent insulinotropic polypeptide.

Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio, USA.
Diabetes care (Impact Factor: 7.74). 03/2010; 33(7):1561-6. DOI: 10.2337/dc09-2021
Source: PubMed

ABSTRACT Restoration of insulin secretion is critical for the treatment of type 2 diabetes. Exercise and diet can alter glucose-induced insulin responses, but whether this is due to changes in beta-cell function per se is not clear. The mechanisms by which lifestyle intervention may modify insulin secretion in type 2 diabetes have also not been examined but may involve the incretin axis.
Twenty-nine older, obese (aged 65 +/- 1 years; BMI 33.6 +/- 1.0 kg/m(2)) subjects, including individuals with newly diagnosed type 2 diabetes (obese-type 2 diabetic) and individuals with normal glucose tolerance (obese-NGT), underwent 3 months of nutritional counseling and exercise training. beta-Cell function (oral glucose-induced insulin secretion corrected for insulin resistance assessed by hyperinsulinemic-euglycemic clamps) and the role of glucose-dependent insulinotropic polypeptide (GIP) were examined.
After exercise and diet-induced weight loss (-5.0 +/- 0.7 kg), oral glucose-induced insulin secretion was increased in the obese-type 2 diabetic group and decreased in the obese-NGT group (both P < 0.05). When corrected for alterations in insulin resistance, the change in insulin secretion remained significant only in the obese-type 2 diabetic group (1.23 +/- 0.26 vs. 2.04 +/- 0.46 arbitrary units; P < 0.01). Changes in insulin secretion were directly related to the GIP responses to oral glucose (r = 0.64, P = 0.005), which were augmented in the obese-type 2 diabetic group and only moderately suppressed in the obese-NGT group.
After lifestyle-induced weight loss, improvements in oral glucose-induced insulin secretion in older, obese, nondiabetic subjects seem to be largely dependent on improved insulin sensitivity. However, in older obese diabetic patients, improved insulin secretion is a consequence of elevated beta-cell function. We demonstrate for the first time that changes in insulin secretion after lifestyle intervention may be mediated via alterations in GIP secretion from intestinal K-cells.

0 Bookmarks
 · 
116 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite positive effects of incretins on insulin secretion, little is known about the effect of exercise on these hormones. Metformin can affect incretin concentrations and is prescribed to a large proportion of people with diabetes. We, therefore, examined the effects of aerobic exercise and/or metformin on incretin hormones. Ten participants with type 2 diabetes were recruited for this randomized crossover study. Metformin or placebo was given for 28 days, followed by the alternate treatment for 28 days. On the last 2 days of each condition, participants were assessed during a non-exercise day and a subsequent exercise day. Aerobic exercise took place in the morning and blood samples were taken in the subsequent hours (before and after lunch). Aerobic exercise did not increase total plasma glucagon-like peptide-1 (GLP-1) or glucose-dependent insulinotropic polypeptide (GIP) in the pre- or post-lunch periods (all p>0.1). GLP-1 was higher in the pre-lunch (p=0.016) and post-lunch (p=0.018) periods of the metformin conditions compared with the placebo. Total plasma GIP was higher in the pre-lunch period (p=0.05), but not in the post-lunch period (p=0.95), with metformin compared with placebo. In contrast to our hypothesis, aerobic exercise did not acutely increase total GLP-1 and GIP levels in patients with type 2 diabetes. Metformin, independent of exercise, significantly increased total plasma GLP-1 and GIP concentrations in these patients.
    Canadian Journal of Diabetes 12/2013; 37(6):375-80. · 0.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have shown that exercise could improve β-cell function in humans or animal models of type 2 diabetes. However, whether it can prevent the progression of pre-diabetes to diabetes remains unclear. To study the effects of exercise on glycolipid metabolism, β-cell function, and insulin resistance in the non-diabetic young offsprings of diabetic patients. One hundred and eighty-two normal glucose tolerance young offsprings of type 2 diabetic parents were enrolled. Individuals with fasting insulin ≥12.0 mU/L were assigned to hyperinsulinemia group (n = 72) and those with fasting insulin <12.0 mU/L were assigned to normal group (n = 110). The subjects in hyperinsulinemia group received 12-week exercise intervention. A 75-g oral glucose tolerance test and insulin release test were conducted before and after intervention. The area under curve of glucose (AUCglu), area under curve of insulin (AUCINS), HOMA insulin resistance index (HOMA-IR), HOMA β-cell function (HOMA-β), and early insulin secretion index (ΔI 30/ΔG 30) were calculated. Body composition was measured by dual energy X-ray absorptiometry. At baseline, AUCINS and HOMA-β in hyperinsulinemia group were significantly higher compared with the normal group (P < 0.05). After the 12-week exercise intervention, no significant changes in blood pressure, body mass index, blood glucose, serum lipids, and percentage of body fat were found in hyperinsulinemia group; however, AUCINS, HOMA-β, HOMA-IR (P < 0.05) and ΔI 30/ΔG 30 (P < 0.01) were significantly decreased. Exercise is effective for preventing pre-diabetic insulin resistance and β-cell dysfunction in non-diabetic young offsprings of diabetic patients.
    Journal of endocrinological investigation 01/2014; · 1.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: After food ingestion, the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted by the intestines into circulation where they act on the pancreas to promote insulin secretion. We evaluated the hypothesis that low postprandial plasma insulin levels in lean exercise-trained individuals are associated with low concentrations of incretin hormones. A cross-sectional study was performed to compare postprandial incretin hormone levels in lean endurance exercise-trained individuals (EX; n = 14, ≥ 40 yr) and age- and sex-matched, non-obese, sedentary control subjects (CON, n = 14). The main outcome measures were GLP-1, GIP, insulin, and glucose incremental areas under the curve (AUC) as measured in plasma samples collected during a 2-hr,75-g oral glucose tolerance test (OGTT). The EX group had lower body fat percentage (14.6 ± 1.1% vs. 23.3 ± 1.7%, p = 0.0002) and higher maximal oxygen uptake (53 ± 2 vs. 34 ± 2, p < 0.0001) than CON. Glucose AUC did not differ between groups (p = 0.20). Insulin AUC was lower in EX (2.5 ± 0.5 vs. 4.2 ± 1.2 μU/mL·min·1000, p = 0.02). No differences were observed between groups (EX and CON, respectively) for GLP-1 AUC (3.5 ± 0.7 vs. 4.1 ± 1.1 pmol·min/L·100, p = 0.61) or GIP AUC (19.2 ± 1.4 vs. 18.0 ± 1.4 pg·min/mL·1000; p = 0.56). In CON, insulin AUC was correlated with AUCs for GLP-1 (r = 0.53, p = 0.05) and GIP (r = 0.71, p = 0.004) but no such correlations were observed in EX (both p ≥ 0.67). Low postprandial insulin levels in lean exercise-trained individuals are not attributable to lower incretin hormone concentrations. However, exercise may decrease the dependency of postprandial insulin levels on incretin hormones.
    Medicine and science in sports and exercise 02/2014; · 4.48 Impact Factor

Full-text (2 Sources)

View
65 Downloads
Available from
Jun 3, 2014