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This Article Full Text Full Text (PDF) All Versions of this Article: 296/6/E1269    most recent 00112.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kelly, K. R. Articles by Kirwan, J. P. PubMed PubMed Citation Articles by Kelly, K. R. Articles by Kirwan, J. P.

The glucose-dependent insulinotropic polypeptide and glucose-stimulated insulin response to exercise training and diet in obesity

¹Department of Pathobiology, Lerner Research Institute; ²Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic; ³Department of Nutrition, School of Medicine, Case Western Reserve University; and ⁴Department of Gastroenterology/Hepatology, Cleveland Clinic, Cleveland, Ohio

Submitted 18 February 2009 ; accepted in final form 2 April 2009

Aging and obesity are characterized by decreased β-cell sensitivity and defects in the potentiation of nutrient-stimulated insulin secretion by GIP. Exercise and diet are known to improve glucose metabolism and the pancreatic insulin response to glucose, and this effect may be mediated through the incretin effect of GIP. The purpose of this study was to assess the effects of a 12-wk exercise training intervention (5 days/wk, 60 min/day, 75% O_{2 max}) combined with a eucaloric (EX, n = 10) or hypocaloric (EX-HYPO, pre: 1,945 ± 190, post: 1,269 ± 70, kcal/day; n = 9) diet on the GIP response to glucose in older (66.8 ± 1.5 yr), obese (34.4 ± 1.7 kg/m²) adults with impaired glucose tolerance. In addition to GIP, plasma PYY_3–36, insulin, and glucose responses were measured during a 3-h, 75-g oral glucose tolerance test. Both interventions led to a significant improvement in O_{2 max} (P < 0.05). Weight loss (kg) was significant in both groups but was greater after EX-HYPO (–8.3 ± 1.1 vs. –2.8 ± 0.5, P = 0.002). The glucose-stimulated insulin response was reduced after EX-HYPO (P = 0.02), as was the glucose-stimulated GIP response (P < 0.05). Furthermore, after the intervention, changes in insulin (I_0–30/G_0–30) and GIP (_0–30) secretion were correlated (r = 0.69, P = 0.05). The PYY_3–36 (_0–30) response to glucose was increased after both interventions (P < 0.05). We conclude that 1) a combination of caloric restriction and exercise reduces the GIP response to ingested glucose, 2) GIP may mediate the attenuated glucose-stimulated insulin response after exercise/diet interventions, and 3) the increased PYY_3–36 response represents an improved capacity to regulate satiety and potentially body weight in older, obese, insulin-resistant adults.

incretins; weight loss; insulin resistance; gut hormones