title: Acute administration of unacylated ghrelin has no effect on Basal or stimulated insulin secretion in healthy humans.
abstract: Unacylated ghrelin (UAG) is the predominant ghrelin isoform in the circulation. Despite its inability to activate the classical ghrelin receptor, preclinical studies suggest that UAG may promote β-cell function. We hypothesized that UAG would oppose the effects of acylated ghrelin (AG) on insulin secretion and glucose tolerance. AG (1 µg/kg/h), UAG (4 µg/kg/h), combined AG+UAG, or saline were infused to 17 healthy subjects (9 men and 8 women) on four occasions in randomized order. Ghrelin was infused for 30 min to achieve steady-state levels and continued through a 3-h intravenous glucose tolerance test. The acute insulin response to glucose (AIRg), insulin sensitivity index (SI), disposition index (DI), and intravenous glucose tolerance (kg) were compared for each subject during the four infusions. AG infusion raised fasting glucose levels but had no effect on fasting plasma insulin. Compared with the saline control, AG and AG+UAG both decreased AIRg, but UAG alone had no effect. SI did not differ among the treatments. AG, but not UAG, reduced DI and kg and increased plasma growth hormone. UAG did not alter growth hormone, cortisol, glucagon, or free fatty acid levels. UAG selectively decreased glucose and fructose consumption compared with the other treatments. In contrast to previous reports, acute administration of UAG does not have independent effects on glucose tolerance or β-cell function and neither augments nor antagonizes the effects of AG.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Cincinnati, Cincinnati, OH jenny.tong@uc.edu.
authors.forename: Jenny
authors.initials: J
authors.lastname: Tong
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Cincinnati, Cincinnati, OH.
authors.forename: Harold W
authors.initials: HW
authors.lastname: Davis
authors.affiliation: Clinical Translational Research Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Summer
authors.affiliation: Department of Psychiatry, University of Cincinnati, Cincinnati, OH.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Benoit
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Cincinnati, Cincinnati, OH.
authors.forename: Ahrar
authors.initials: A
authors.lastname: Haque
authors.affiliation: Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bidlingmaier
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Cincinnati, Cincinnati, OHInstitute for Obesity and Diabetes, Helmholtz Center Munich and Division of Metabolic Diseases, Department of Medicine, Technical University, Munich, Germany.
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Tschöp
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Cincinnati, Cincinnati, OHCincinnati Veterans Affairs Medical Center, Cincinnati, OH.
authors.forename: David
authors.initials: D
authors.lastname: D'Alessio
mesh_terms: D000293:Adolescent; D000328:Adult; D001481:Basal Metabolism / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D054439:Ghrelin / Q000008:administration & dosage*; D006262:Health; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin