Olanzapine treatment is associated with reduced high molecular weight adiponectin in serum: a potential mechanism for olanzapine-induced insulin resistance in patients with schizophrenia.
Identifieur interne : 000433 ( Ncbi/Curation ); précédent : 000432; suivant : 000434Olanzapine treatment is associated with reduced high molecular weight adiponectin in serum: a potential mechanism for olanzapine-induced insulin resistance in patients with schizophrenia.
Auteurs : Ayanthi A. Richards [Australie] ; Ingrid J. Hickman ; Amy Y-H Wang ; Amanda L. Jones ; Felicity Newell ; Bryan J. Mowry ; Jonathan P. Whitehead ; Johannes B. Prins ; Graeme A. MacdonaldSource :
- Journal of clinical psychopharmacology [ 0271-0749 ] ; 2006.
Descripteurs français
- KwdFr :
- Adipocytes (), Adipocytes (métabolisme), Adiponectine (), Adiponectine (sang), Adulte, Benzodiazépines (effets indésirables), Benzodiazépines (usage thérapeutique), Cellules cultivées, Femelle, Glycémie (métabolisme), Humains, Insulinorésistance, Masse moléculaire, Mâle, Neuroleptiques (effets indésirables), Neuroleptiques (usage thérapeutique), Schizophrénie (), Schizophrénie (traitement médicamenteux).
- MESH :
- effets indésirables : Benzodiazépines, Neuroleptiques.
- métabolisme : Adipocytes, Glycémie.
- sang : Adiponectine.
- traitement médicamenteux : Schizophrénie.
- usage thérapeutique : Benzodiazépines, Neuroleptiques.
- Adipocytes, Adiponectine, Adulte, Cellules cultivées, Femelle, Humains, Insulinorésistance, Masse moléculaire, Mâle, Schizophrénie.
English descriptors
- KwdEn :
- Adipocytes (drug effects), Adipocytes (metabolism), Adiponectin (blood), Adiponectin (chemistry), Adult, Antipsychotic Agents (adverse effects), Antipsychotic Agents (therapeutic use), Benzodiazepines (adverse effects), Benzodiazepines (therapeutic use), Blood Glucose (metabolism), Cells, Cultured, Female, Humans, Insulin Resistance, Male, Molecular Weight, Olanzapine, Schizophrenia (complications), Schizophrenia (drug therapy).
- MESH :
- chemical , adverse effects : Antipsychotic Agents, Benzodiazepines.
- chemical , blood : Adiponectin.
- chemical , chemistry : Adiponectin.
- complications : Schizophrenia.
- drug effects : Adipocytes.
- drug therapy : Schizophrenia.
- metabolism : Adipocytes, Blood Glucose.
- chemical , therapeutic use : Antipsychotic Agents, Benzodiazepines.
- Adult, Cells, Cultured, Female, Humans, Insulin Resistance, Male, Molecular Weight, Olanzapine.
Abstract
Treatment of schizophrenia with olanzapine and other atypical antipsychotic agents is associated with insulin resistance and diabetes mellitus. The mechanism for this is not understood. Adiponectin is an insulin-sensitizing cytokine secreted by adipocytes. It is present in serum in multimers of varying size. Trimers and hexamers are referred to as low molecular weight (LMW) adiponectin. Larger multimers (12-, 18-, and 24-mers) have been designated high molecular weight (HMW) adiponectin and seem responsible for the insulin-sensitizing action of this adipokine. The aim of this study was to examine total adiponectin and LMW and HMW multimers in serum from patients with schizophrenia treated with either olanzapine (n = 9) or other typical antipsychotics (n = 9) and compare results with 16 healthy sex-, body mass index-, and age-matched controls. The effects of olanzapine on adiponectin protein expression and secretion in in vitro-differentiated primary human adipocytes were also examined. Patients receiving olanzapine had significantly lower total serum adiponectin as compared with those on conventional treatment and controls (5.23 +/- 1.53 ng/mL vs. 8.20 +/- 3.77 ng/mL and 8.78 +/- 3.8 ng/mL; P < 0.05 and P < 0.01, respectively). The HMW adiponectin was also reduced in patients on olanzapine as compared with the disease and healthy control groups (1.67 +/- 0.96 ng/mL vs. 3.87 +/- 2.69 ng/mL and 4.07 +/- 3.2 ng/mL; P < 0.05 for both). The LMW adiponectin was not different between patient groups (P = 0.15) but lower in patients on olanzapine as compared with controls (3.56 +/- 0.85 ng/mL vs. 4.70 +/- 1.4 ng/mL; P < 0.05). In vitro, short duration (up to 7 days) olanzapine exposure had no effect on total adiponectin expression or multimer composition of secreted protein. In summary, this study demonstrates a correlation between olanzapine treatment and reduced serum adiponectin, particularly HMW multimers. This may not be a direct effect of olanzapine on adipocyte expression or secretion of adiponectin. These observations provide insights into possible mechanisms for the association between olanzapine treatment and insulin resistance.
DOI: 10.1097/01.jcp.0000218404.64619.52
PubMed: 16702887
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Jones</name></author><author><name sortKey="Newell, Felicity" sort="Newell, Felicity" uniqKey="Newell F" first="Felicity" last="Newell">Felicity Newell</name></author><author><name sortKey="Mowry, Bryan J" sort="Mowry, Bryan J" uniqKey="Mowry B" first="Bryan J" last="Mowry">Bryan J. Mowry</name></author><author><name sortKey="Whitehead, Jonathan P" sort="Whitehead, Jonathan P" uniqKey="Whitehead J" first="Jonathan P" last="Whitehead">Jonathan P. Whitehead</name></author><author><name sortKey="Prins, Johannes B" sort="Prins, Johannes B" uniqKey="Prins J" first="Johannes B" last="Prins">Johannes B. Prins</name></author><author><name sortKey="Macdonald, Graeme A" sort="Macdonald, Graeme A" uniqKey="Macdonald G" first="Graeme A" last="Macdonald">Graeme A. 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The mechanism for this is not understood. Adiponectin is an insulin-sensitizing cytokine secreted by adipocytes. It is present in serum in multimers of varying size. Trimers and hexamers are referred to as low molecular weight (LMW) adiponectin. Larger multimers (12-, 18-, and 24-mers) have been designated high molecular weight (HMW) adiponectin and seem responsible for the insulin-sensitizing action of this adipokine. The aim of this study was to examine total adiponectin and LMW and HMW multimers in serum from patients with schizophrenia treated with either olanzapine (n = 9) or other typical antipsychotics (n = 9) and compare results with 16 healthy sex-, body mass index-, and age-matched controls. The effects of olanzapine on adiponectin protein expression and secretion in in vitro-differentiated primary human adipocytes were also examined. Patients receiving olanzapine had significantly lower total serum adiponectin as compared with those on conventional treatment and controls (5.23 +/- 1.53 ng/mL vs. 8.20 +/- 3.77 ng/mL and 8.78 +/- 3.8 ng/mL; P < 0.05 and P < 0.01, respectively). The HMW adiponectin was also reduced in patients on olanzapine as compared with the disease and healthy control groups (1.67 +/- 0.96 ng/mL vs. 3.87 +/- 2.69 ng/mL and 4.07 +/- 3.2 ng/mL; P < 0.05 for both). The LMW adiponectin was not different between patient groups (P = 0.15) but lower in patients on olanzapine as compared with controls (3.56 +/- 0.85 ng/mL vs. 4.70 +/- 1.4 ng/mL; P < 0.05). In vitro, short duration (up to 7 days) olanzapine exposure had no effect on total adiponectin expression or multimer composition of secreted protein. In summary, this study demonstrates a correlation between olanzapine treatment and reduced serum adiponectin, particularly HMW multimers. This may not be a direct effect of olanzapine on adipocyte expression or secretion of adiponectin. These observations provide insights into possible mechanisms for the association between olanzapine treatment and insulin resistance.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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