Circulating Obestatin Concentration is Lowered by Insulin in Rats

Abstract

Circulating obestatin is lowered by food intake, but factors involved in obestatin regulation remain unclear. The aim of this study was to determine whether intravenous glucose or insulin infusion lowers obestatin. Rats were infused over 3 h with either A. saline (controls); B. dextrose to steady state blood glucose ~16.7 mM, or C. insulin 7.5 mU/kg.min, plus dextrose as needed to clamp to euglycemic basal concentrations. During 3 h of infusion, group B had significantly greater (P<0.01) glucose, 18.75±1.27 mM, than groups A (6.10±0.33 mM) or C (6.19±0.18 mM). Groups B and C had hyperinsulinemia at the end of the 3 h infusion (1.02±0.03 ng/ml, 1.07±0.02 ng/ml) compared with saline-infused (0.38±0.01 ng/ml, P<0.01). Obestatin concentrations were significantly reduced (P<0.01) in both hyperinsulinemic groups and (B=0.95±0.06 ng/ml; C=0.87±0.04 ng/ml) versus controls (1.56±0.13 ng/ml). These data suggest that insulin can decrease the plasma obestatin levels.

Key words

hormones - metabolic features - obesity

*

^* These authors contributed equally to this work.

• References

• 1 Anderwald-Stadler M, Krebs M, Promintzer M et al. Plasma obestatin is lower at fasting and not suppressed by insulin in insulin-resistant humans. Am J Physiol Endocrinol Metab 2007; 293: E1393-E1398
• 2 Granata R, Settanni F, Gallo D et al. Obestatin promotes survival of pancreatic beta-cells and human islets and induces expression of genes involved in the regulation of beta-cell mass and function. Diabetes 2008; 57: 967-979
• 3 Green BD, Irwin N, Flatt PR. Direct and indirect effects of obestatin peptides on food intake and the regulation of glucose homeostasis and insulin secretion in mice. Peptides 2007; 28: 981-987
• 4 Guo ZF, Zheng X, Qin YW et al. Circulating preprandial ghrelin to obestatin ratio is increased in human obesity. J Clin Endocrinol Metab 2007; 92: 1875-1880
• 5 Guo ZF, Ren AJ, Zheng X et al. Different responses of circulating ghrelin, obestatin levels to fasting, re-feeding and different food compositions, and their local expressions in rats. Peptides 2008; 29: 1247-1254
• 6 Holst B, Egerod KL, Schild E et al. GPR39 signaling is stimulated by zinc ions but not by obestatin. Endocrinology 2007; 148: 13-20
• 7 Lauwers E, Landuyt B, Arckens L et al. Obestatin does not activate orphan G protein-coupled receptor GPR39. Biochem Biophys Res Commun 2006; 351: 21-325
• 8 Qader SS, Håkanson R, Rehfeld JF et al. Proghrelin-derived peptides influence the secretion of insulin, glucagon, pancreatic polypeptide and somatostatin: a study on isolated islets from mouse and rat pancreas. Regul Pept 2008; 146: 230-237
• 9 Qi X, Li L, Yang G et al. Circulating obestatin levels in normal subjects and in patients with impaired glucose regulation and type 2 diabetes mellitus. Clin Endocrinol (Oxf) 2007; 66: 593-597
• 10 Ren AJ, Guo ZF, Wang YK et al. Obestatin, obesity and diabetes. Peptides 2009; 30: 439-444
• 11 Ren AJ, Guo ZF, Wang YK et al. Inhibitory effect of obestatin on glucose-induced insulin secretion in rats. Biochem Biophys Res Commun 2008; 369: 969-972
• 12 Seoane LM, Al-Massadi O, Pazos Y et al. Central obestatin administration does not modify either spontaneous or ghrelin-induced food intake in rats. J Endocrinol Invest 2006; 29: RC13-RC15
• 13 Zhang JV, Ren PG, Avsian-Kretchmer O et al. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin′s effects on food intake. Science 2005; 310: 996-999