Acute Effects of Atypical Antipsychotics on Whole-Body Insulin Resistance in Rats: Implications for Adverse Metabolic Effects
| Autor: | David E. Johnson, E. Michael Gibbs, William J. Zavadoski, Karen L. Houseknecht, Hans Rollema, Alan Robertson |
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| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class medicine.medical_treatment Glucose uptake Atypical antipsychotic Pharmacology Benzodiazepines Insulin resistance Internal medicine Hyperinsulinemia Animals Insulin Medicine Rats Wistar Muscle Skeletal Antipsychotic Clozapine Pancreatic hormone Metabolic Syndrome Dose-Response Relationship Drug business.industry medicine.disease Rats Disease Models Animal Psychiatry and Mental health Glucose Endocrinology Liver Olanzapine Hyperglycemia Acute Disease Insulin Resistance Energy Metabolism Somatostatin business Antipsychotic Agents medicine.drug |
| Zdroj: | Neuropsychopharmacology. 32:289-297 |
| ISSN: | 1740-634X 0893-133X |
| DOI: | 10.1038/sj.npp.1301209 |
| Popis: | Although it is generally accepted that atypical antipsychotics differ in their risk for diabetic side effects, the underlying pharmacological mechanisms are unknown. Studies on the mechanisms of antipsychotic-induced hyperglycemia or insulin resistance are often confounded by the concomitant weight gain and dyslipidemia, known diabetic risk factors. To investigate whether antipsychotics can acutely cause metabolic effects before any change in body composition, we studied the effects of four atypical antipsychotics on whole-body insulin resistance. Using the hyperinsulinemic, euglycemic clamp technique in conscious rats, insulin and somatostatin were infused at a constant rate to provide constant hyperinsulinemia and to suppress pancreatic insulin secretion. Glucose was infused at a variable rate, adjusted to maintain euglycemia. At steady state, animals were administered vehicle (V) or antipsychotic and the glucose infusion rate was monitored as an index of insulin sensitivity. Clamp experiments using radiotracers and studies on glucose uptake into isolated skeletal muscle were conducted to differentiate between effects on hepatic glucose production (HGP) and on peripheral glucose uptake. Olanzapine (OLAN) and clozapine (CLOZ) acutely impaired whole-body insulin sensitivity in a dose-dependent manner (P |
| Databáze: | OpenAIRE |
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