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Submitted on July 5, 2005
Accepted on April 10, 2006
Institute 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.), Institute of Digestive Diseases (P.M.P.) and Institute of Otorhinolaryngology (V.B.D.), Belgrade University School of Medicine, Dr Subotica 13, 11000 Belgrade, Serbia
* To whom correspondence should be addressed. 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: To reveal the effect of ghrelin on insulin-mediated glucose disposal in gastrectomized patients.
Study: Double-blind randomized placebo-controlled study.
Setting: Hospital based study.
Patients: Seven men and three women who all had a previous total gastrectomy and truncal vagotomy entered and completed study.
Intervention: Each individual received infusion of saline alone or saline with ghrelin (5.0 pmol/kg/min) during 5-hour hyperinsulinemic (80 mU · m-2 · min-1)-euglycemic clump on two separate days.
Main outcome measures: Glucose disposal rate and concentrations of C-peptide, ghrelin, growth hormone (GH), insulin-like growth factor I (IGF-I), IGF binding protein-3 (IGFBP-3) and IGFBP-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-1·min-1 P < 0.001). In experiment 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 while leptin significantly rose (P < 0.001). In ghrelin infused study, 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 control study (P < 0.001). Other hormones and IGFBPs changed similarly as in 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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