-
Views
-
Cite
Cite
Christopher H. S. McIntosh, Irene Bremsak, Francis C. Lynn, Ruth Gill, Simon A. Hinke, Richard Gelling, Cuilan Nian, Gary McKnight, Stephen Jaspers, Raymond A. Pederson, Glucose-Dependent Insulinotropic Polypeptide Stimulation of Lipolysis in Differentiated 3T3-L1 Cells: Wortmannin-Sensitive Inhibition by Insulin
*, Endocrinology, Volume 140, Issue 1, 1 January 1999, Pages 398–404, https://doi.org/10.1210/endo.140.1.6464This work was supported by grants from Zymogenetics Inc. (Seattle, WA), the Medical Research Council of Canada (5–90007-RAP/CHSM) and the Canadian Diabetes Association (CHSM/RAP).
Close - Share Icon Share
Abstract
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 (10−9–10−7m) + IBMX increased cAMP production by 1180–2246%. The adenylyl cyclase inhibitor MDL 12330A (10−4m) 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 β-cell responsiveness to stimulation by glucose and GIP.
