Acute effects of acylated ghrelin on salbutamol-induced metabolic actions in humans
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ORIGINAL ARTICLE
Acute effects of acylated ghrelin on salbutamol-induced metabolic actions in humans A. Benso • E. Gramaglia • I. Olivetti • M. Tomelini • S. Belcastro • E. Calvi • A. Dotta • D. St-Pierre • E. Ghigo • F. Broglio
Received: 22 January 2014 / Accepted: 18 June 2014 Ó Springer Science+Business Media New York 2014
Abstract The aim of this study is to describe a potential modulatory effect of acute acylated ghrelin (AG) administration on the glucose, insulin, and free fatty acids (FFA) responses to salbutamol (SALBU). Six healthy young male volunteers underwent the following four testing sessions in random order at least 7 days apart: (a) acute AG administration (1.0 lg/kg i.v. as bolus at 00 ); (b) SALBU infusion (0.06 lg/kg/min i.v. from -150 to ?450 ); (c) SALBU infusion ? AG; and (d) isotonic saline infusion. Blood samples for glucose, insulin, and FFA levels were collected every 15 min. As expected, with respect to saline, SALBU infusion induced a remarkable increase in glucose (10.8 ± 5.6 mmol/l 9 min; P \ 0.05), insulin (2436.8 ± 556.9 pmol/l 9 min; P \ 0.05), and FFA (18.9 ± 4.5 mmol/l 9 min; P \ 0.01) levels. A significant increase in glucose (7.4 ± 3.9 mmol/l 9 min; P \ 0.05) and FFA levels (10.0 ± 2.8 mmol/l 9 min; P \ 0.01) without significant variations in insulin levels were recorded after AG administration. Interestingly, the hyperglycemic effect of AG appeared to be significantly potentiated during SALBU infusion (26.7 ± 4.8 mmol/l 9 min; P \ 0.05). On the other hand, the stimulatory effect of SALBU on insulin and FFA was not significantly modified by AG administration. The results of this study show that acute AG administration has a synergic effect with b2-adrenergic receptor activation by SALBU on blood glucose increase, suggesting that their pharmacological hyperglycemic action takes place via A. Benso E. Gramaglia I. Olivetti M. Tomelini S. Belcastro E. Calvi A. Dotta D. St-Pierre E. Ghigo F. Broglio (&) Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, A.O. Citta` della Salute e della Scienza – Molinette, Corso Dogliotti 14, 10126 Turin, Italy e-mail: [email protected]
different mechanisms. On the other hand, AG has a negligible influence on the other pharmacological metabolic effects of SALBU infusion. Keywords Ghrelin Salbutamol b-adrenergic system Insulin Glucose Free fatty acids
Introduction Acylated ghrelin (AG) has been discovered as an endogenous ligand of the growth hormone secretagogue (GHS) receptor (GHS-R) type 1a [1], which expression has been localized in the hypothalamus–pituitary unit, in several endocrine glands as well as in the liver, muscle, adipocytes, and pancreas [2]. Ghrelin strongly stimulates GH release but it is also known to exert a broad spectrum of other actions among which the control of energy metabolism and food intake has been extensively evaluated [3, 4]. The adrenergic system plays a major role in the modulation of metabolic functions [5] and in energy e
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