ABSTRACT
AIMS/HYPOTHESIS: The aim of this study was to determine whether rapid conversion to inactive and potentially antagonistic peptides could alter the response to GLP-1. METHODS: We evaluated the ability of exendin-4, a GLP-1 analogue resistant to degradation by dipeptidyl peptidase IV, to modulate insulin-induced stimulation of glucose uptake and suppression of glucose production in eight healthy subjects during infusion of GLP-1 (1.2 pmol.kg(-1).min(-1)), exendin-4 (0.12 pmol.kg(-1).min(-1)), or saline. Glucose was clamped at 5.3 mmol/l and insulin was infused to progressively increase insulin concentrations to about 65, 190 and 700 pmol/l, respectively. Endogenous insulin secretion was inhibited with somatostatin to ensure comparable portal insulin concentrations while glucagon and growth hormone were maintained at basal concentrations. RESULTS: Glucose, insulin, C-peptide, glucagon and growth hormone concentrations did not differ on the three occasions. In contrast, cortisol concentrations were greater during both exendin-4 (25.1+/-4.4 mmol/l per 7 h; p<0.01) and GLP-1, (17.0+/-2.0 mmol/l 7 h; p<0.05) than saline (13.5+/-1.5 mmol/l per 7 h). While insulin-induced stimulation of glucose disappearance at the highest insulin concentrations tended to be greater and insulin-induced suppression of glucose production lower in the presence of exendin-4 or GLP-1 than saline, the differences were not significant. CONCLUSION/INTERPRETATION: Exendin-4 and GLP-1 increase cortisol secretion in human subjects. However, neither alters insulin action in non-diabetic human subjects. These data also suggest that the lack of an effect of GLP-1 on insulin action is not likely to be explained by rapid degradation to inactive or antagonistic peptides.
Subject(s)
Blood Glucose/metabolism , Insulin/blood , Peptide Fragments/pharmacology , Peptides/pharmacology , Venoms/pharmacology , Adult , Animals , Biotransformation , Blood Glucose/drug effects , Body Mass Index , C-Peptide/blood , Dipeptidyl Peptidase 4/metabolism , Exenatide , Glucagon/blood , Glucagon-Like Peptide 1 , Glucagon-Like Peptides , Human Growth Hormone/blood , Humans , Hydrocortisone/blood , Infusions, Intravenous , Kinetics , Lizards , Peptide Fragments/administration & dosage , Peptides/administration & dosage , Peptides/pharmacokinetics , Reference ValuesABSTRACT
Tourette Syndrome is a neurological disorder of unknown origin. The individual suffering from Tourette Syndrome encounters tics and often additional behaviors such as speech, sleep, and learning difficulties, as well as social isolation.
