Metabolic effects of chronic obestatin infusion in rats.
Obestatin is purported to be a peptide hormone encoded in preproghrelin. We studied the metabolic effects of continuous infusion of obestatin via subcutaneously implanted osmotic mini-pumps. Administration of up to 500nmol/kg body weight/day obestatin did not change 24h cumulative food intake or body weight in rats. Similarly, no effects were observed when obestatin was infused at 1000nmol/kg body weight/day for seven days. This dose of obestatin infused during a 24h fast did not alter weight loss, suggesting that obestatin has no effect on energy expenditure, and this dose did not alter glucose or insulin responses during an IPGTT. Obestatin was originally proposed to interact with GPR39 and subsequently the receptor for GLP-1. While both receptors are expressed in pancreatic islets, incubation with obestatin did not alter insulin release from islets in vitro. Moreover, obestatin did not bind to INS-1 beta-cells or HEK cells overexpressing GLP-1 receptors or displace GLP-1 binding to these cells. Our findings do not support the concept that obestatin is a hormone with metabolic actions.
Department of Cellular, Life Sciences Centre, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
Suraj
S
Unniappan
Madeleine
M
Speck
Timothy J
TJ
Kieffer
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology*; D000067757:Glucagon-Like Peptide-1 Receptor; D005951:Glucose Tolerance Test; D007263:Infusions, Parenteral; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects; D018027:Receptors, Glucagon / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D013995:Time
C000593833:GLP1R protein, human; C495797:GPR39 protein, human; D054439:Ghrelin; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D008055:Lipids; D043562:Receptors, G-Protein-Coupled; D018027:Receptors, Glucagon