Atypical antipsychotic drugs directly impair insulin action in adipocytes: effects on glucose transport, lipogenesis, and antilipolysis.

Atypical antipsychotic drugs directly impair insulin action in adipocytes: effects on glucose transport, lipogenesis, and antilipolysis. Research Abstract Details 

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Atypical antipsychotic drugs directly impair insulin action in adipocytes: effects on glucose transport, lipogenesis, and antilipolysis. Abstract Text:

Julia Engl,Maria Rettenbacher,Wolfgang W Fleischhacker,Christoph F Ebenbichler,Julia Engl,Maria Rettenbacher,Wolfgang W Fleischhacker,Christoph F Ebenbichler,

Treatment with second-generation antipsychotics (SGAs) has been associated with weight gain and the development of diabetes mellitus, although the mechanisms are unknown. We tested the hypothesis that SGAs exert direct cellular effects on insulin action and substrate metabolism in adipocytes. We utilized two cultured cell models including 3T3-L1 adipocytes and primary cultured rat adipocytes, and tested for effects of SGAs risperidone (RISP), clozapine (CLZ), olanzapine (OLZ), and quetiapine (QUE), together with conventional antipsychotic drugs butyrophenone (BUTY), and trifluoperazine (TFP), over a wide concentration range from 1 to 500 microM. The effects of antipsychotic drugs on basal and insulin-stimulated rates of glucose transport were studied at 3 h, 15 h, and 3 days. Both CLZ and OLZ (but not RISP) at doses as low as 5 microM were able to significantly decrease the maximal insulin-stimulated glucose transport rate by approximately 40% in 3T3-L1 cells, whereas CLZ and RISP reduced insulin-stimulated glucose transport rates in primary cultured rat adipocytes by approximately 50-70%. Conventional drugs (BUTY and TFP) did not affect glucose transport rates. Regarding intracellular glucose metabolism, both SGAs (OLZ, QUE, RISP) and conventional drugs (BUTY and TFP) increased basal and/or insulin-stimulated glucose oxidation rates, whereas rates of lipogenesis were increased by CLZ, OLZ, QUE, and BUTY. Finally, rates of lipolysis in response to isoproterenol were reduced by the SGAs (CLZ, OLZ, QUE, RISP), but not by BUTY or TFP. These experiments demonstrate that antipsychotic drugs can differentially affect insulin action and metabolism through direct cellular effects in adipocytes. However, only SGAs were able to impair the insulin-responsive glucose transport system and to impair lipolysis in adipocytes. Thus, SGAs directly induce insulin resistance and alter lipogenesis and lipolysis in favor of progressive lipid accumulation and adipocyte enlargement. These effects of SGAs on adipocytes could explain, in part, the association of SGAs with weight gain and diabetes.

Atypical antipsychotic drugs directly impair insulin action in adipocytes: effects on glucose transport, lipogenesis, and antilipolysis. Publishing Authors By Initials

J Engl,M Rettenbacher,WW Fleischhacker,CF Ebenbichler,J Engl,M Rettenbacher,WW Fleischhacker,CF Ebenbichler,

For similar animals: chordata: vertebrates: mammals: rodentia: muridae: murinae: rats: rats, wistar research abstracts see: animals: chordata: vertebrates: mammals: rodentia: muridae: murinae: rats: rats, wistar research

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Atypical antipsychotic drugs directly impair insulin action in adipocytes: effects on glucose transport, lipogenesis, and antilipolysis. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Neuropsychopharmacology : official publication of

VOLUME: 32

Page Numbers: 765-72

Journal Abbreviation: Neuropsychopharmacology

ISSN: 0893-133X

DAY: 28

MONTH: 06

YEAR: 2006

Atypical antipsychotic drugs directly impair insulin action in adipocytes: effects on glucose transport, lipogenesis, and antilipolysis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8904907

Atypical antipsychotic drugs directly impair insulin action in adipocytes: effects on glucose transport, lipogenesis, and antilipolysis. Keywords Mesh Terms:

KEYWORDS: Rats, Wistar

MESH TERMS: drug effects

Chemical & Substance for Abstract: Atypical antipsychotic drugs directly impair insulin action in adipocytes: effects on glucose transport, lipogenesis, and antilipolysis. Information

Substance Name: Glucose

Registry Number: 50-99-7

Grant and Affiliation Information for Atypical antipsychotic drugs directly impair insulin action in adipocytes: effects on glucose transport, lipogenesis, and antilipolysis.

AFFILIATION: Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294-3360, USA. helliner@uab.edu

Country: United States

AGENCY: United States NIDDK

GRANT: DK-38765

ACRONYM: DK

MEDLINETA: Neuropsychopharmacology

REFSOURCE: Neuropsychopharmacology. 2007 Nov;32(11)

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