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Acute Effects of Ghrelin on Insulin Secretion and Glucose Disposal Rate in Gastrectomized Patients

Institutes of Endocrinology, Diabetes, and Diseases of Metabolism (S.S.D., N.M.L., M.S.P., A.J., D.M., K.S.L., L.L., M.D.), Digestive Diseases (P.M.P.), and Otorhinolaryngology (V.B.D.), Belgrade University School of Medicine, 11000 Belgrade, Serbia

Address all correspondence and requests for reprints to: Svetozar S. Damjanovic, Institute of Endocrinology, Diabetes, and Diseases of Metabolism, Dr Subotica 13, 11000 Beograd, Serbia. E-mail: sova{at}net.yu.

Context: Plasma ghrelin concentration is diminished in gastrectomized patients. Acute ghrelin administration reduces insulin secretion, whereas insulin infusion has been shown to decrease ghrelin levels. Whether ghrelin has any effect on glucose utilization in humans is unknown.

Objective: Our objective was to reveal the effect of ghrelin on insulin-mediated glucose disposal in gastrectomized patients.

Study and Setting: We conducted a double-blind, randomized, placebo-controlled, hospital-based study.

Patients: Seven men and three women who all had a previous total gastrectomy and truncal vagotomy entered and completed the study.

Intervention: Each individual received infusion of saline alone or saline with ghrelin (5.0 pmol/kg·min) during a 5-h hyperinsulinemic (80 mU/m²·min) euglycemic clamp on 2 separate days.

Main Outcome Measures: We assessed glucose disposal rate and concentrations of C-peptide, ghrelin, GH, IGF-I, IGF-binding protein (IGFBP)-3 and -1, cortisol, leptin, and adiponectin.

Results: Glucose disposal rate decreased during ghrelin infusion (control study 8.6 ± 0.2 vs. 7.2 ± 0.1 mg/kg·min P < 0.001). In experiments with saline infusion, levels of ghrelin (P < 0.001), C-peptide (P < 0.001), glucagon (P < 0.001), adiponectin (P = 0.005), cortisol (P = 0.012), IGF-I (P < 0.001), IGFBP-3 (P = 0.038), and IGFBP-1 (P = 0.001) fell in response to euglycemic hyperinsulinemia. GH concentration maintained at baseline, whereas leptin significantly rose (P < 0.001). In the ghrelin infusion study, the plateau level of ghrelin concentration (6963.6 ± 212.9 pg/ml) was maintained from 90 min throughout the experiment. GH (P < 0.001) and cortisol (P = 0.04) concentrations rose, whereas C-peptide levels were more suppressed than in the control study (P < 0.001). Other hormones and IGFBPs changed similarly as in the study with saline infusion.

Conclusion: It appears that ghrelin might be involved in the negative control of insulin secretion and glucose consumption in gastrectomized patients, at least after acute administration.

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