title: Ghrelin Impairs Prandial Glucose Tolerance and Insulin Secretion in Healthy Humans Despite Increasing GLP-1.
abstract: OBJECTIVE
  Administration of ghrelin inhibits the acute insulin response to glucose and worsens IV glucose tolerance in healthy subjects. Evidence from preclinical studies suggests that ghrelin may have differential effects on glucose metabolism during fasting and feeding. Our objective was to test the effects of ghrelin on glucose and insulin responses during a meal tolerance test.
  
  
  METHODS
  Acyl ghrelin (0.26 and 2.0 μg/kg/h) or saline was infused in 13 healthy subjects on three separate occasions in randomized order. Ghrelin was infused for 45 minutes to achieve steady-state levels and continued for 240 minutes after ingestion of a liquid test meal. Primary outcomes were area under the curve for glucose and insulin secretion.
  
  
  RESULTS
  We found that ghrelin infusions of 0.26 and 2.0 μg/kg/h raised steady-state plasma total ghrelin levels to 1.7- and 4.8-fold above fasting concentrations, but did not alter fasting plasma glucose or insulin levels. During the meal tolerance test, ghrelin decreased insulin sensitivity, impaired β-cell function, and induced glucose intolerance. The high-dose ghrelin infusion also raised postprandial glucagon like peptide 1 secretion without affecting glucose dependent insulinotropic polypeptide, glucagon, or peptide YY concentrations.
  
  
  CONCLUSIONS
  We conclude that both physiologic and pharmacologic doses of ghrelin worsen the glucose and β-cell responses to meal ingestion in healthy humans. The increase in postprandial glucagon like peptide 1 secretion by ghrelin suggests a novel enteroendocrine connection, but does not mitigate the glucose intolerance.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism (J.T., H.W.D., D.D.), Department of Medicine, University of Cincinnati, Cincinnati, Ohio; Institute of Clinical Physiology (A.G.), National Research Council, Pisa, Italy; Cincinnati VA Medical Center (D.D.), Cincinnati, Ohio.
authors.forename: Jenny
authors.initials: J
authors.lastname: Tong
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism (J.T., H.W.D., D.D.), Department of Medicine, University of Cincinnati, Cincinnati, Ohio; Institute of Clinical Physiology (A.G.), National Research Council, Pisa, Italy; Cincinnati VA Medical Center (D.D.), Cincinnati, Ohio.
authors.forename: Harold W
authors.initials: HW
authors.lastname: Davis
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism (J.T., H.W.D., D.D.), Department of Medicine, University of Cincinnati, Cincinnati, Ohio; Institute of Clinical Physiology (A.G.), National Research Council, Pisa, Italy; Cincinnati VA Medical Center (D.D.), Cincinnati, Ohio.
authors.forename: Amalia
authors.initials: A
authors.lastname: Gastaldelli
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism (J.T., H.W.D., D.D.), Department of Medicine, University of Cincinnati, Cincinnati, Ohio; Institute of Clinical Physiology (A.G.), National Research Council, Pisa, Italy; Cincinnati VA Medical Center (D.D.), Cincinnati, Ohio.
authors.forename: David
authors.initials: D
authors.lastname: D'Alessio
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D054439:Ghrelin / Q000494:pharmacology*; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D019894:Peptide YY / Q000097:blood; D019518:Postprandial Period / Q000187:drug effects*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D019894:Peptide YY; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon