Posted by Quintal on June 14, 2007, at 17:22:28
In reply to Zyprexa's effect on blood sugar, posted by Jesus is Savior on June 14, 2007, at 16:08:47
Role of Drugs and M3 Receptors in Insulin Secretion
In a recent study, investigators using transgenic mice with either organ-specific absence or overexpression of pancreatic M3 receptors produced opposite effects on insulin secretion.3 Total absence of β-cell M3 receptors resulted in a marked decrease in insulin secretion and glucose intolerance, while overexpression of M3 receptors in the pancreas caused overproduction of insulin and lower plasma glucose levels. This study offers the most compelling evidence to date that M3 receptors in the pancreas have a vital role in regulating insulin secretion. These findings, coupled with those of previous studies4,5 showing that M3 receptors control the secretion of insulin in response to glucose, have profound implications for clinical psychopharmacology.
The atypical antipsychotics olanzapine and clozapine have been found to block insulin secretion mediated by muscarinic receptor activation. Both of these agents act as potent muscarinic receptor antagonists, with resultant undesirable metabolic effects leading to glucose intolerance and diabetes.4 Concentrations as low as 10–100 nmol/L of both of these drugs significantly impaired cholinergic-potentiated secretion of insulin. These concentrations fall well within the range of therapeutic free plasma levels of both drugs. In this animal model, neither glucose infusion alone nor administration of three other antipsychotics—risperidone, haloperidol, or ziprazodone—were found to adversely affect insulin response.