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Association of Acylated and Nonacylated Ghrelin with Insulin Sensitivity in Overweight and Obese Postmenopausal Women

Département de Nutrition (D.H.S.-P., F.M., J.F., D.M., R.R.-L.) and Médecine (L.C.), Université de Montréal, Montréal, Québec, Canada H3C 3J7; Département de Kinanthropologie (A.D.K.), Université du Québec à Montréal, Montréal, Québec, Canada H3C 3P8; Faculté d’Éducation Physique et Sportive (M.B.), Université de Sherbrooke, Sherbrooke, Québec, Canada J1K 2R1; Institut National de la Santé et de la Recherche Médicale U680 (J.-P.B.), Faculté de Médecine Saint-Antoine et Service de Biochimie et Hormonologie, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Université Pierre et Marie Curie, 75020 Paris, France; Centre de Recherche Hôpital Laval (K.C.), Université Laval, Québec, Canada G1K 7P4; and School of Human Kinetics (E.D., P.I.), Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada K1N 6N5

Address all correspondence and requests for reprints to: Rémi Rabasa-Lhoret, M.D., Ph.D., Faculté de Médecine, Département de Nutrition, Université de Montréal, 2405 Chemin Cote Ste-Catherine, Pavillon Liliane de Stewart, Montréal, Québec, Canada H3T 1A8. E-mail: remi.rabasa-lhoret{at}umontreal.ca.

Objective: Ghrelin [acylated (AG) and nonacylated (NAG)] has been shown to play a pivotal role in the regulation of food intake and insulin sensitivity. It is presently unclear whether variation in insulin sensitivity is related to AG and NAG levels in obese individuals. To address this issue, we determined whether insulin-sensitive overweight or obese (ISO) and insulin-resistant overweight or obese (IRO) individuals display different total ghrelin (TotG), AG, and NAG profiles during a euglycemic/hyperinsulinemic clamp (EHC).

Design: Eighty-nine nondiabetic overweight and obese postmenopausal women underwent EHC to evaluate insulin sensitivity. Body composition and blood lipid profiles were assessed. Subjects within the highest tertile of insulin sensitivity were described as ISO (n = 31), whereas those within the lowest tertile of insulin sensitivity were considered as IRO (n = 29). Plasma TotG, AG, and NAG profiles were assessed by RIA at 0, 60, 160, 170, and 180 min during the EHC.

Results: TotG and NAG levels were significantly decreased for ISO and IRO individuals during the EHC, whereas only ISO subjects displayed a significant reduction of AG concentrations (P < 0.05). AG area under the curve value and the ratio of AG/NAG (fasting and area under the curve) were significantly decreased in ISO individuals. Furthermore, maximal reduction of TotG and AG concentrations was greater in ISO compared with IRO individuals (P < 0.05). Insulin sensitivity was significantly correlated with maximal reduction of TotG (r = 0.36; P < 0.01) and AG (r = 0.36; P < 0.05) concentrations.

Conclusion: The dysregulation of ghrelin secretion profiles during EHC is associated with insulin resistance. AG may contribute to the variation of insulin sensitivity in overweight or obese postmenopausal women.

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