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This Article Full Text Full Text (PDF) All Versions of this Article: 293/5/E1393    most recent 00330.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Anderwald-Stadler, M. Articles by Anderwald, C. Search for Related Content PubMed PubMed Citation Articles by Anderwald-Stadler, M. Articles by Anderwald, C.

Plasma obestatin is lower at fasting and not suppressed by insulin in insulin-resistant humans

¹Third Medical Department of Metabolic Diseases and Nephrology; ²Karl Landsteiner Institute of Metabolic Diseases and Nephrology, Hietzing Hospital; ³Department of Emergency Medicine; and ⁴Division of Endocrinology and Metabolism, Third Department of Internal Medicine, Medical University Vienna, Vienna, Austria

Submitted 27 May 2007 ; accepted in final form 27 August 2007

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 nondiabetic individuals with high (IS; n = 18, 13 females and 5 males, age 47 ± 2 yr, BMI = 25.5 ± 0.9 kg/m²) and low (IR; n = 18, 12 females and 6 males, age 45 ± 2 yr, P = 0.49, BMI = 27.5 ± 1.1 kg/m², P = 0.17) insulin-stimulated glucose disposal (M), measured by 2-h hyperinsulinemic (40 mU·min^–1·m^–2) isoglycemic clamp tests. M_{100–120 min} was higher in IS (10.7 ± 0.7) than in IR (4.4 ± 0.2 mg·min^–1·kg^–1, P < 10^–9), whereas 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 pg/ml 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 correlated positively 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 nondiabetic humans. Furthermore, plasma obestatin is reduced by insulin in insulin-sensitive but not in insulin-resistant persons.

ghrelin; hyperinsulinemic clamp test; free fatty acids; appetite regulation