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Forskolin Inhibition of Glucose Metabolism in Rat Adipocytes Independent of Adenosine 3',5'-Monophosphate Accumulation and Lipolysis^*

IRA MILLS, FRANCISCO J. MORENO and JOHN N. FAIN

Section of Biochemistry, Brown University Providence, Rhode Island 02912

Abstract

Addition of forskolin (1 µM) to rat adipocytes incubated with insulin and 0.2 mM glucose inhibited glucose metabolism in the absence of any significant stimulation of either cAMP accumulation or lipolysis. The action of forskolin was in contrast to that of isoproterenol, since forskolin inhibited [1-¹⁴C]glucose conversion to total lipid, whereas isoproterenol had the opposite effect. Elevation of the medium glucose concentration to 10 mM reversed the inhibitory effects of forskolin on glucose metabolism. The ability of forskolin to inhibit glucose metabolism was observed whether glucose was labeled in the 1 or the 6 position. The results of the present study suggest that forskolin affects glucose metabolism independently of adenylate cyclase activation. (Endocrinology 115: 1066–1069, 1984)

Footnotes

^* This work was supported by USPHS Grants AM-10149 and AM-21470.

Postdoctoral trainee of the NIADDK (AM-07187). To whom requests for reprints should be addressed.

Present address: Departmento de Bioquimica y Biologia Molecular, Universidad Autonoma de Madrid, Madrid, Spain.

Received March 29, 1984.

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