Submitted on May 27, 2007
Accepted on August 27, 2007
Plasma Obestatin is Lower at Fasting and Not Suppressed by Insulin in Insulin-Resistant Humans
Marietta Stadler1, Michael Krebs2, Miriam Promintzer2, Martina Mandl2, Martin G. Bischof3, Peter Nowotny2, Thomas Kaestenbauer4, Anton Luger2, Rudolf Prager5, and Christian Anderwald6*
1 3rd Medical Department of Metabolic Diseases and Nephrology, Hietzing Hospital, Vienna, Austria; Karl Landsteiner Institute of Metabolic Diaseases and Nephrology, Vienna, Austria; Department of Emergency Medicine, Medical University Vienna, Vienna, Austria
2 Division of Endocrinology and Metabolism, Department of Internal Medicine 3, Medical University Vienna, Vienna, Austria
3 Department of Internal Medicine III, University of Vienna, Vienna, Austria; Division of Endocrinology and Metabolism, Department of Internal Medicine 3, Medical University Vienna, Vienna, Austria
4 Karl Landsteiner Institute of Metabolic Diaseases and Nephrology, Vienna, Austria
5 3rd Medical Department of Metabolic Diseases and Nephrology, Hietzing Hospital, Vienna, Austria; Karl Landsteiner Institute of Metabolic Diaseases and Nephrology, Vienna, Austria
6 Endocrinology&Metabolism, Internal Medicine 3, Vienna, Austria; Division of Endocrinology and Metabolism, Department of Internal Medicine 3, Medical University Vienna, Vienna, Austria
* To whom correspondence should be addressed. E-mail: christian-heinz.anderwald{at}meduniwien.ac.at.
Obestatin, a recently discovered 23-amino-acid peptide, is involved in the regulation of appetite and body weight in antagonistic fashion to ghrelin, both deriving from a common precursor peptide. Ghrelin was shown to be associated with insulin resistance, which may also affect obestatin.
We investigated the association between insulin resistance and plasma concentrations of obestatin and ghrelin in non-diabetic individuals with high (IS; n=18, 13f/5m, 47±2years, BMI=25.5±0.9 kg/m2) and low (IR; n=18, 12f/6m, 45±2years, p=0.49; BMI=27.5±1.1 kg/m2, p=0.17) insulin-stimulated glucose disposal (M), measured by 2-hour-hyperinsulinemic(40 mU·min-1·m-2) isoglycemic clamp-tests.
M100-120 min was higher in IS (10.7±0.7mg·min-1·kg-1) than in IR (4.4±0.2; p<10-9), while insulin-dependent suppression of free fatty acids (FFA) in plasma was reduced in IR (71±6% vs. IS:82±5%, p<0.02).
In both groups, plasma ghrelin concentrations were comparable at fasting, and similarly reduced by 24-28% during insulin infusion. IR had lower fasting plasma obestatin levels (383±26 vs. IS:469±23 pg/ml; p<0.02). Clamp insulin infusion reduced plasma obestatin to ~81% of basal values in IS (p<0.00002), but not in IR.
Fasting plasma obestatin was positively correlated with M (r=0.34, p=0.04), HDL-cholesterol (r=0.45, p=0.01) and plasma ghrelin concentrations (r=0.80, p<0.000001), and negatively with measures of adiposity, plasma FFA during clamp (r=-0.42, p<0.01), and systolic blood pressure (r=-0.33, p<0.05).
In conclusion, fasting plasma concentrations of obestatin, but not of ghrelin, are reduced in insulin resistance, and are positively associated with whole-body insulin sensitivity in non-diabetic humans. Furthermore, plasma obestatin is reduced by insulin in insulin-sensitive, but not in insulin-resistant persons.
