Effect of chlorpromazine on insulin release in mice: comparison between in vivo and in vitro.

Nakadate, Teruo; Kubota, Katsunari; Nakaki, Toshio; Kato, Ryuichi

doi:10.1254/jjp.32.950

Cited by 5 publications

(2 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other groups that have studied the inhibition of the insulin release by antipsychotics used concentrations of the respective antipsychotics ranging from 1 to 100 mM. 5,[38][39][40][41] There are some restrictions in translating results obtained in the cell culture system of L6 myotubes to the human system. First, this cell line is derived from the rat, thus species-specific differences must be considered.…”

Section: Discussionmentioning

confidence: 99%

Olanzapine impairs glycogen synthesis and insulin signaling in L6 skeletal muscle cells

Engl¹,

Laimer²,

Niederwanger³

et al. 2005

Mol Psychiatry

View full text Add to dashboard Cite

Second-generation antipsychotic agents (SGAs) are increasingly replacing first-generation antipsychotic agents due to their superior activity against the negative symptoms of schizophrenia, decreased extrapyramidal symptoms and better tolerability. However, some SGAs are associated with adverse metabolic effects as significant weight gain, lipid disorders and diabetes mellitus. The pathogenesis of SGA-induced disturbances of glucose homeostasis is unclear. In vivo studies suggest a direct influence of SGAs on peripheral insulin resistance. To this end, we analyzed whether olanzapine might alter glycogen synthesis and the insulin-signaling cascade in L6 myotubes. Glycogen content was diminished in a dose- and time-dependent manner. Within the insulin-signaling cascade IRS-1 tyrosine phosphorylation was induced several fold by insulin and was diminished by preincubation with olanzapine. IRS-1-associated PI3K activity was stimulated by insulin three-fold in L6 myotubes. Olanzapine inhibited insulin-stimulated IRS-1-associated PI3K activity in a dose-dependent manner. Protein mass of AKT, GSK-3 and GS was unaltered, whereas phosphorylation of AKT and GSK-3 was diminished, and pGS was increased. Finally, we compared olanzapine with amisulpride, an SGA clinically not associated with the induction of diabetes mellitus. Glycogen content was diminished in olanzapine-preincubated L6 cells, whereas this effect was not observed under the amisulpride conditions. We conclude that olanzapine impairs glycogen synthesis via inhibition of the classical insulin-signaling cascade and that this inhibitory effect may lead to the induction of insulin resistance in olanzapine-treated patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Olanzapine impairs glycogen synthesis and insulin signaling in L6 skeletal muscle cells

Engl¹,

Laimer²,

Niederwanger³

et al. 2005

Mol Psychiatry

View full text Add to dashboard Cite

show abstract

“…Although the slight increase of glucose stimulated TRI and C-peptide levels was constant throughout the IVGTT, it was not statistically significant. The paradoxical stimulating effect on insulin secretion was proved in experiments on rats also with chiorpromazine (Sato et al, 1988;Nakadate et al, 1982). The authors explain this as a result of hyperglyeaemia conditioned by adrenergic stimulation which overcomes the inhibitory effect proper on the B cell.…”

Section: Discussionmentioning

confidence: 94%

Effect of Calcitriol and Trifluoperazine on Glucose Stimulated B Cell Function in Healthy Humans

Žofková¹,

Stolba²

2009

Exp Clin Endocrinol Diabetes

View full text Add to dashboard Cite

Effects of Chemical Restraint and Anesthesia on Blood Glucose Levels

Gross

1985

Animal Models in Cardiovascular Research

View full text Add to dashboard Cite

Effect of chlorpromazine on insulin release in mice: comparison between in vivo and in vitro.

Cited by 5 publications

References 13 publications

Olanzapine impairs glycogen synthesis and insulin signaling in L6 skeletal muscle cells

Olanzapine impairs glycogen synthesis and insulin signaling in L6 skeletal muscle cells

Effect of Calcitriol and Trifluoperazine on Glucose Stimulated B Cell Function in Healthy Humans

Effects of Chemical Restraint and Anesthesia on Blood Glucose Levels

Contact Info

Product

Resources

About