| Pharmacodynamic characterization of insulin on MDMA-induced thermogenesis. | |
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MedLine Citation:
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PMID: 19482019 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Sympathomimetic drugs (MDMA; ecstasy) induce a potentially catastrophic hyperthermia that involves free fatty acid (FFA) activation of mitochondrial uncoupling proteins (UCP). Insulin is an important regulator of plasma FFA levels, although its role in thermogenesis is unclear. The aims of the present study were 1) to characterize the pharmacodynamic effects of MDMA on plasma insulin and glucose, 2) to examine the effects of insulin on MDMA-induced thermogenesis and 3) to examine MDMA-induced thermogenesis in an animal model of insulin resistance, the obese Zucker rat. Insulin levels peaked 15 min after MDMA (40 mg/kg, s.c.), which preceded the peak temperature change at 60 min. Plasma glucose levels also peaked 15 min. after MDMA and remained elevated throughout the 90-min. monitoring period. Insulin pretreatment (10 units/kg, s.c.) 30 min. before a low dose of MDMA (5 mg/kg, s.c.) potentiated the thermogenic response. Insulin resistant, fa/fa (obese) Zucker rats demonstrated an attenuated thermogenic response to MDMA (40 mg/kg, s.c.). Consistent with the role for FFA in UCP3 expression, immunoblot analysis showed significantly increased levels of UCP3 protein obese compared to lean Zucker skeletal muscle. In conclusion, the results of the present study suggest a potential role of insulin signaling in sympathomimetic-induced thermogenesis. |
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Authors:
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Matthew L Banks; Sarah K Buzard; Candice M Gehret; Alexa N Monroy; M Alexander Kenaston; Edward M Mills; Jon E Sprague |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-05-29 |
Journal Detail:
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Title: European journal of pharmacology Volume: 615 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-06-26 Completed Date: 2009-11-10 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 257-61 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Glucose / metabolism Body Temperature / drug effects Dose-Response Relationship, Drug Energy Metabolism Fatty Acids, Nonesterified / blood, metabolism Hypoglycemic Agents / blood, metabolism* Insulin / blood, metabolism* Insulin Resistance Male N-Methyl-3,4-methylenedioxyamphetamine / toxicity* Obesity / blood, metabolism Rats Rats, Sprague-Dawley Rats, Zucker Sympathomimetics / toxicity* Thermogenesis / drug effects*, physiology |
| Grant Support | |
ID/Acronym/Agency:
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DA022712/DA/NIDA NIH HHS; R15 DA022712-01A1/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Fatty Acids, Nonesterified; 0/Hypoglycemic Agents; 0/Sympathomimetics; 11061-68-0/Insulin; 42542-10-9/N-Methyl-3,4-methylenedioxyamphetamine |
| Comments/Corrections | |
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