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PMID: 2660145 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Sphingosine, an inhibitor of protein kinase C, suppresses the insulin-like effects of growth hormone in rat adipocytes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 86 ·No. 12 ·1989-06-00 ·Pages 4705-9

Smal J, De Meyts P

Abstract

Insulin, human growth hormone (hGH), and phorbol 12-myristate 13-acetate all stimulate lipogenesis in rat adipocytes preincubated without hGH for 4 hr. As previous data suggested that protein kinase C plays an important role in the action of insulin and in the insulin-like effects of hGH in rat adipocytes, we tested the effects of sphingosine, a potent inhibitor of protein kinase C, on the lipogenic activity of both hormones. At 50 microM, sphingosine had no effect on basal lipogenesis but completely abolished the action of phorbol 12-myristate 13-acetate and decreased by 65% and 89%, respectively, the effects of hGH and insulin. At higher concentrations (100 microM), sphingosine abolished both basal and hormone-stimulated lipogenesis; this effect was partially reversible after washing the cells. Similar effects of sphingosine on basal and stimulated glucose uptake were seen in parallel, suggesting that sphingosine inhibits lipogenesis at the glucose-uptake step in rat adipocytes. N-Acetylsphingosine and sphingomyelin, two analogs of sphingosine that are inactive on protein kinase C, did not inhibit lipogenesis induced by hGH, insulin, or phorbol 12-myristate 13-acetate. Sphingosine did not inhibit insulin binding to rat adipocytes at concentrations up to 200 microM but decreased hGH binding to its receptors by 44% at 50 microM. These data suggest a direct link between the inhibition of protein kinase C and that of lipogenesis and provide new evidence for the involvement of protein kinase C in the mechanism of action of growth hormone and insulin in rat adipocytes.

MeSH Terms
Adipose Tissue/drug effects,metabolism Animals Cells, Cultured Glucose/metabolism Growth Hormone/pharmacology Insulin/pharmacology Kinetics Lipids/biosynthesis Male Protein Kinase C/antagonists & inhibitors Rats Rats, Inbred Strains Receptor, Insulin/metabolism Receptors, Somatotropin/metabolism Sphingosine/pharmacology Structure-Activity Relationship Tetradecanoylphorbol Acetate/pharmacology
Chemicals
Insulin Lipids Receptors, Somatotropin Growth Hormone Receptor, Insulin Protein Kinase C Glucose Sphingosine Tetradecanoylphorbol Acetate
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Smal J
Department of Diabetes, Endocrinology and Metabolism, City of Hope National Medical Center, Duarte, CA 91010.
De Meyts P
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.86.12.4705
Published
1989-06-00
Pages
4705-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC287340
Subset
IM
Grants
NCI NIH HHS · CA 33572-09 · United States
External Links
PubMed source DOI: 10.1073/pnas.86.12.4705 PMC Full Text View journal details
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