Glucose-dependent insulinotropic polypeptide modulates adipocyte lipolysis and reesterification.
OBJECTIVE
Glucose-dependent insulinotropic polypeptide (GIP) is an incretin released from intestinal K-cells during the postprandial period. Previous studies have suggested that GIP may play an etiologic role in obesity; thus, the GIP receptor may represent a target for anti-obesity drugs. The present studies were conducted to elucidate mechanisms by which GIP might promote obesity by examining the effect of GIP on both glycerol release (indicative of lipolysis) and free fatty acid (FFA) release (indicative of both lipolysis and reesterification), as well as the ability of a GIP-specific receptor antagonist (ANTGIP) to attenuate these effects.


METHODS
Isolated rat adipocytes were perifused on a column with 10 nM GIP alone or in combination with 10 microU/mL insulin, 1 microM isoproterenol, or 1 microM ANTGIP. Samples were collected every minute and assayed for FFA, glycerol, and lactate.


RESULTS
GIP significantly increased FFA reesterification (decreased FFA release by 25%), stimulated lipolysis (increased glycerol release by 22%), and attenuated the lipolytic response to isoproterenol by 43%. These properties were similar to those of insulin in vitro, suggesting that GIP possesses insulin-like lipogenic effects on adipocytes. Finally, ANTGIP reversed the effects of GIP on both basal and stimulated adipocyte metabolism.


CONCLUSIONS
These studies provide further evidence for an important physiological role for GIP in lipid homeostasis and possibly in the pathogenesis of obesity. They also suggest that the GIP receptor may represent an excellent target for the prevention and treatment of obesity and obesity-related type 2 diabetes.
Getty-Kaushik
Lisa
L
Obesity Research Center, Department of Molecular Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Song
Diane H
DH
Boylan
Michael O
MO
Corkey
Barbara E
BE
Wolfe
M Michael
MM
D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000517:prevention & control; D004951:Esterification / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005749:Gastric Inhibitory Polypeptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005765:Gastrointestinal Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D050356:Lipid Metabolism; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D011964:Receptors, Gastrointestinal Hormone / Q000037:antagonists & inhibitors*
D005230:Fatty Acids, Nonesterified; D005765:Gastrointestinal Agents; D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor