详细记录  
题名:Effects of intracerebroventricular (ICV) olanzapine on insulin sensitivity and secretion in vivo: An animal model.
作者:HAHN MK; CHINTOH A; REMINGTON G; TEO C; MANN S; ARENOVICH T; FLETCHER P; LAM L; NOBREGA J; GUENETTE M; COHN T; GIACCA A;
来源:Eur Neuropsychopharmacol. 2014 Mar;24(3):448-58. doi: [ IF= 0.00 ] ]
URL :10.1016/j.euroneuro.2013.07.011
日期:20140408
摘要:The atypical antipsychotics (AAPs) have been associated with an increased risk of
type 2 diabetes. While weight gain associated with AAPs is a risk factor for
diabetes, preclinical work suggests that among these medications, olanzapine,
when given peripherally in a single dose, causes pronounced effects on insulin
sensitivity and secretion. Given a critical role of the hypothalamus in control
of glucose metabolism, we examined the effect of central administration of
olanzapine. Sprague-Dawley rats were treated with a single 75mug
intracerebroventricular (ICV) dose of olanzapine and tested using separate
hyperinsulinemic-euglycemic and hyperglycemic clamps. Dosing of olanzapine was
established based on inhibition of amphetamine-induced locomotion. In contrast to
the single dosing peripheral paradigm, there was no effect of central olanzapine
on insulin sensitivity, either with respect to hepatic glucose production or
peripheral glucose uptake. Analogous to the peripheral model, a single ICV dose
of olanzapine followed by the hyperglycemic clamp decreased insulin (p=0.0041)
and C-peptide response (p=0.0039) to glucose challenge as compared to vehicle,
mirrored also by a decrease in the steady state glucose infusion rate required to
maintain hyperglycemia (p=0.002). In conclusion, we demonstrate novel findings
that at least part of the effect of olanzapine on beta-cell function in vivo is
central.

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