Acute effects of ghrelin on insulin secretion and glucose disposal rate in gastrectomized patients.
BACKGROUND
Plasma ghrelin concentration is diminished in gastrectomized patients. Acute ghrelin administration reduces insulin secretion, whereas insulin infusion has been shown to decrease ghrelin levels. Whether ghrelin has any effect on glucose utilization in humans is unknown.


OBJECTIVE
Our objective was to reveal the effect of ghrelin on insulin-mediated glucose disposal in gastrectomized patients. STUDY AND SETTING: We conducted a double-blind, randomized, placebo-controlled, hospital-based study.


METHODS
Seven men and three women who all had a previous total gastrectomy and truncal vagotomy entered and completed the study.


METHODS
Each individual received infusion of saline alone or saline with ghrelin (5.0 pmol/kg.min) during a 5-h hyperinsulinemic (80 mU/m(2).min) euglycemic clamp on 2 separate days.


METHODS
We assessed glucose disposal rate and concentrations of C-peptide, ghrelin, GH, IGF-I, IGF-binding protein (IGFBP)-3 and -1, cortisol, leptin, and adiponectin.


RESULTS
Glucose disposal rate decreased during ghrelin infusion (control study 8.6 +/- 0.2 vs. 7.2 +/- 0.1 mg/kg.min P < 0.001). In experiments with saline infusion, levels of ghrelin (P < 0.001), C-peptide (P < 0.001), glucagon (P < 0.001), adiponectin (P = 0.005), cortisol (P = 0.012), IGF-I (P < 0.001), IGFBP-3 (P = 0.038), and IGFBP-1 (P = 0.001) fell in response to euglycemic hyperinsulinemia. GH concentration maintained at baseline, whereas leptin significantly rose (P < 0.001). In the ghrelin infusion study, the plateau level of ghrelin concentration (6963.6 +/- 212.9 pg/ml) was maintained from 90 min throughout the experiment. GH (P < 0.001) and cortisol (P = 0.04) concentrations rose, whereas C-peptide levels were more suppressed than in the control study (P < 0.001). Other hormones and IGFBPs changed similarly as in the study with saline infusion.


CONCLUSIONS
It appears that ghrelin might be involved in the negative control of insulin secretion and glucose consumption in gastrectomized patients, at least after acute administration.
Damjanovic
Svetozar S
SS
Institute of Endocrinology, Diabetes, and Diseases of Metabolism, Dr Subotica 13, 11000 Beograd, Serbia. sova@net.yu
Lalic
Nebojsa M
NM
Pesko
Predrag M
PM
Petakov
Milan S
MS
Jotic
Aleksandra
A
Miljic
Dragana
D
Lalic
Katarina S
KS
Lukic
Ljiljana
L
Djurovic
Marina
M
Djukic
Vojko B
VB
D052242:Adiponectin / Q000097:blood; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005743:Gastrectomy; D054439:Ghrelin; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007700:Kinetics; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D036361:Peptide Hormones / Q000008:administration & dosage* / Q000097:blood / Q000502:physiology; D010919:Placebos
D052242:Adiponectin; D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D020738:Leptin; D036361:Peptide Hormones; D010919:Placebos; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D005934:Glucagon; D006854:Hydrocortisone