Clozapine impairs insulin action by up-regulating Akt phosphorylation and Ped/Pea-15 protein abundance.
Bottom Line: Clozapine reduced insulin-stimulated glucose uptake in PC12 and in L6 cells, representative models of neuron and skeletal muscle, respectively.Consistently, clozapine reduced insulin effect on insulin receptor (IR) by 40% and on IR substrate-1 (IRS1) tyrosine phosphorylation by 60%.Insulin-stimulated Akt phosphorylation was also reduced by about 40%.
Affiliation: Dipartimento di Neuroscienze, Sezione di Psichiatria, Laboratorio di Psichiatria Molecolare, University of Napoli Federico II, Napoli, Italy.Show MeSH
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Mentions: Protein extracts from CP and cortex were obtained and assayed by Western blot with specific antibodies. In the animals treated with clozapine, increased levels of phosphorylated Akt were detected in CP (Fig. 8A), but not in cortex. This was paralleled by increased Ped/Pea-15 detection (Fig. 8B) and reduced PKC-ζ phosphorylation in CP (Fig. 8C). Again, no difference was detected in cortex of the treated animals.
Affiliation: Dipartimento di Neuroscienze, Sezione di Psichiatria, Laboratorio di Psichiatria Molecolare, University of Napoli Federico II, Napoli, Italy.