| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
Department of Physiology (C.H.S.M., I.B., F.C.L., R.G., S.A.H., R.G., C.N., R.A.P.), University of British Columbia, Vancouver, British Columbia, V6T1Z3, Canada; and Zymogenetics, Inc. (G.M., S.J.), Seattle, Washington
Address all correspondence and requests for reprints to: Christopher McIntosh, Ph.D., Department of Physiology, Faculty of Medicine, University of British Columbia, 2146 Health Sciences Mall, Vancouver, British Columbia, Canada, V6T 1Z3. E-mail: mcintoch{at}unixg.ubc.ca
GIP is an important insulinotropic hormone (incretin) that has also been implicated in fat metabolism. There is controversy regarding the actions of GIP on adipocytes. In the current study, the existence of GIP receptors and effects of GIP on lipolysis were studied in differentiated 3T3-L1 cells. GIP receptor messenger RNA was detected by RT-PCR and RNase protection assay. Receptors were detected in binding studies (IC50 26.7 ± 0.7 nM). GIP stimulated glycerol release with an EC50 of 3.28 ± 0.63 nM. GIP (10-9–10-7 M) + IBMX increased cAMP production by 1180–2246%. The adenylyl cyclase inhibitor MDL 12330A (10-4 M) inhibited GIP-induced glycerol production by >90%, and reduced cAMP responses to basal. Preincubation of 3T3-L1 cells with insulin inhibited glycerol responses to GIP, and the inhibitory effect of insulin was blocked by the phosphatidylinositol 3'-kinase inhibitor, wortmannin. It is concluded that GIP stimulates glycerol release in 3T3-L1 cells primarily via stimulation of cAMP production, and that insulin antagonizes GIP-induced lipolysis in a wortmannin-sensitive fashion. It is suggested that effects of GIP on fat metabolism in vivo may depend upon the circulating insulin level, and that meal-released GIP may elevate circulating fatty acids, thus optimizing pancreatic ß-cell responsiveness to stimulation by glucose and GIP.
This article has been cited by other articles:
 |
|
 |
|
  S.-J. Kim, C. Nian, and C. H. S. McIntosh Resistin Is a Key Mediator of Glucose-dependent Insulinotropic Polypeptide (GIP) Stimulation of Lipoprotein Lipase (LPL) Activity in Adipocytes J. Biol. Chem., November 23, 2007; 282(47): 34139 - 34147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-J. Kim, C. Nian, and C. H. S. McIntosh Activation of Lipoprotein Lipase by Glucose-dependent Insulinotropic Polypeptide in Adipocytes: A ROLE FOR A PROTEIN KINASE B, LKB1, AND AMP-ACTIVATED PROTEIN KINASE CASCADE J. Biol. Chem., March 23, 2007; 282(12): 8557 - 8567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Akesson, B. Ahren, V. C. Manganiello, L. S. Holst, G. Edgren, and E. Degerman Dual Effects of Pituitary Adenylate Cyclase-Activating Polypeptide and Isoproterenol on Lipid Metabolism and Signaling in Primary Rat Adipocytes Endocrinology, December 1, 2003; 144(12): 5293 - 5299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. Mayo, L. J. Miller, D. Bataille, S. Dalle, B. Goke, B. Thorens, and D. J. Drucker International Union of Pharmacology. XXXV. The Glucagon Receptor Family Pharmacol. Rev., March 1, 2003; 55(1): 167 - 194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Ehses, S. S. T. Lee, R. A. Pederson, and C. H. S. McIntosh A New Pathway for Glucose-dependent Insulinotropic Polypeptide (GIP) Receptor Signaling. EVIDENCE FOR THE INVOLVEMENT OF PHOSPHOLIPASE A2 IN GIP-STIMULATED INSULIN SECRETION J. Biol. Chem., June 22, 2001; 276(26): 23667 - 23673. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
