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Am J Physiol Endocrinol Metab (April 7, 2009). doi:10.1152/ajpendo.00112.2009
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Submitted on February 18, 2009
Revised on April 2, 2009
Accepted on April 2, 2009

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

Karen R Kelly1, Latina M Brooks1, Thomas P.J. Solomon1, Sangeeta Kashyap2, Valerie B O'Leary1, and John P. Kirwan2*

1 Cleveland Clinic
2 Cleveland Clinic Foundation

* To whom correspondence should be addressed. E-mail: kirwanj{at}ccf.org.

Aging and obesity are characterized by decreased {beta}-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-week exercise training intervention (5 days/wk, 60 min/day, 75% VO2max), combined with a eucaloric (EX, N=10), or hypocaloric (EX-HYPO, pre: 1945±190, post: 1269±70, kcal/d, N=9) diet on the GIP response to glucose in older (66.8±1.5 y), obese (34.4±1.7 kg/m2) adults with impaired glucose tolerance. In addition to GIP, plasma PYY3-36, insulin, and glucose responses were measured during a 3-h 75-g oral glucose tolerance test. Both interventions led to a significant improvement in VO2max (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 both interventions (P=0.02). The glucose-stimulated GIP response was significantly reduced after EX-HYPO (P=0.02), as was the glucose-stimulated GIP response (P<0.05). Further, after the intervention, changes in insulin ({Delta}I0-30/{Delta}G0-30) and GIP ({Delta}0-30) secretion were correlated (r=0.69, P=0.05). The PYY3-36 ({Delta}0-30) response to glucose was increased after both interventions (P<0.05). We conclude that 1) the 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 PYY3-36 response represents improved capacity to regulate satiety and potentially body weight in older, obese, insulin resistant adults.







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