کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
338371 547935 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Atypical antipsychotics and effects of muscarinic, serotonergic, dopaminergic and histaminergic receptor binding on insulin secretion in vivo: An animal model
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Atypical antipsychotics and effects of muscarinic, serotonergic, dopaminergic and histaminergic receptor binding on insulin secretion in vivo: An animal model
چکیده انگلیسی

The atypical antipsychotics (AAPs) have been associated with increased risk of type-2 diabetes. Evidence suggests direct, drug-related effects independent of weight gain and although mechanisms underlying this phenomenon are unclear, it has been suggested that the heterogeneous receptor binding profile of the AAPs may influence receptors implicated in glucose metabolism. This study aimed to clarify weight gain-independent mechanisms of AAP-induced changes in insulin secretion by deconstructing their binding profile with representative antagonists. Healthy rats were pretreated with a single subcutaneous dose of darifenacin 6 mg/kg (n = 10), a selective M3 muscarinic antagonist; ketanserin 2 mg/kg (n = 10), a 5HT2A antagonist; raclopride 0.3 mg/kg (n = 11) a selective D2/D3 antagonist; terfenadine 20 mg/kg (n = 9) a selective H1 antagonist; or, vehicle (n = 11). Hyperglycemic clamps were employed following injection, providing an index of secretory capacity of pancreatic β-cells. Acute treatment with darifenacin and ketanserin significantly decreased insulin response to glucose challenge as compared to controls, which was confirmed in the darifenacin group by reduced C-peptide levels. Treatment with raclopride resulted in an increased insulin response and a strong tendency to increased C-peptide levels. H1 blockade did not result in effects on insulin or C-peptide. Results suggest that the effects of antipsychotics on glucose dysregulation may be related to direct inhibitory effects of muscarinic (M3) and serotonergic (5HT2) antagonism on insulin secretion. Based on the expression of D2-like receptors in β-cells, which mediate inhibition of insulin secretion, we propose that prolonged D2 blockade with antipsychotics may predispose to depletion of insulin stores and an eventual defect in pancreatic compensation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Schizophrenia Research - Volume 131, Issues 1–3, September 2011, Pages 90–95
نویسندگان
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