Insulin-dependent modulation of plasma ghrelin and leptin concentrations is less pronounced in type 2 diabetic patients.
The gastric peptide ghrelin augments and the adipocyte-derived hormone leptin reduces appetite and food intake. In the central nervous system, insulin directly decreases hunger sensation but could also act indirectly by modulating ghrelin and leptin secretion. This study examines dose-dependent effects of insulin on plasma ghrelin and leptin concentrations during hyperinsulinemic (1, 2, and 4 mU x kg(-1) x min(-1))-euglycemic clamp tests in six nondiabetic (control subjects) and six type 2 diabetic patients. Type 2 diabetic patients were studied before and after prolonged (12-h and 67-h) variable intravenous insulin treatment aiming at near-normoglycemia (115 +/- 4 mg/dl). Nondiabetic subjects were also studied during saline infusion, which did not affect ghrelin but decreased leptin by 19 +/- 6% (P < 0.03). In control subjects, plasma ghrelin decreased at all clamp steps (-17 +/- 1, -27 +/- 6, and -33 +/- 4%, respectively; P < 0.006 vs. baseline), whereas leptin increased by 35 +/- 11% (P < 0.05). In type 2 diabetic patients without insulin treatment, ghrelin decreased by 18 +/- 7% (P < 0.05) only after 4 mU x kg(-1) x min(-1) insulin infusion and leptin increased by 19 +/- 6% (P < 0.05). After prolonged insulin treatment and near-normoglycemia, ghrelin and leptin remained unchanged in type 2 diabetic patients during the clamps. In conclusion, insulin reduces plasma ghrelin in nondiabetic patients and, to a lesser extent, in type 2 diabetic patients before insulin therapy. These findings indicate an indirect effect of insulin via ghrelin on the suppression of hunger sensation and appetite.
Anderwald
Christian
C
Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna Medical School, Vienna, Austria.
Brabant
Georg
G
Bernroider
Elisabeth
E
Horn
Rüdiger
R
Brehm
Attila
A
Waldhäusl
Werner
W
Roden
Michael
M
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D054439:Ghrelin; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000378:metabolism; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007328:Insulin / Q000097:blood* / Q000494:pharmacology; D007700:Kinetics; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D036361:Peptide Hormones / Q000097:blood*; D012016:Reference Values; D012044:Regression Analysis
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D006442:Glycated Hemoglobin; D019382:Human Growth Hormone; D007328:Insulin; D020738:Leptin; D036361:Peptide Hormones