The Role of I1-Imidazoline Receptors and a2-Adrenergic Receptors in the Modulation of Glucose and Lipid Metabolism in the SHROB Model of Metabolic Syndrome X
Autor: | Richard J. Koletsky, Rodney A. Velliquette, Paul Ernsberger |
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Rok vydání: | 2003 |
Předmět: |
Male
medicine.medical_specialty Receptors Drug medicine.medical_treatment Imidazoline receptor Blood Pressure Biology Rilmenidine Glucagon General Biochemistry Genetics and Molecular Biology Insulin resistance History and Philosophy of Science Receptors Adrenergic alpha-2 Rats Inbred SHR Internal medicine medicine Animals Humans Obesity Receptor Oxazoles Adrenergic alpha-Antagonists Antihypertensive Agents Benzofurans Metabolic Syndrome Moxonidine General Neuroscience Insulin Imidazoles Glucagon secretion Yohimbine Glucose Tolerance Test Lipid Metabolism medicine.disease Rats Disease Models Animal Glucose Endocrinology Female Imidazoline Receptors medicine.drug |
Zdroj: | Annals of the New York Academy of Sciences. 1009:251-261 |
ISSN: | 0077-8923 |
DOI: | 10.1196/annals.1304.031 |
Popis: | Hypertension is commonly accompanied by obesity, hyperlipidemia, and insulin resistance in humans, a cluster of abnormalities known as metabolic syndrome X. With the notable exception of inhibitors of the renin-angiotensin system, which have mildly beneficial effects on insulin resistance, most antihypertensive agents worsen one or more components of metabolic syndrome X. Second-generation centrally acting antihypertensive agents such as rilmenidine and moxonidine have mixed effects on components of metabolic syndrome X, which might reflect in part actions on two different receptors: I(1)-imidazoline and alpha(2)-adrenergic. Using a rat model of metabolic syndrome X, we sought to separate the influence of these two receptors on glucose and lipid metabolism by using selective antagonists. Rilmenidine and moxonidine acutely raised glucose and lowered insulin, thereby further worsening glucose tolerance. These effects were entirely mediated by alpha(2)-adrenergic receptors. Rilmenidine and moxonidine also lowered glucagon, an effect that was mediated solely by I(1)-imidazoline receptors since it was potentiated by alpha(2)-blockade, but eliminated in the presence of I(1)-antagonists. Lowering of triglyceride and cholesterol levels followed the same pattern as glucagon, implicating I(1)-imidazoline receptors in lipid-lowering actions. Chronic treatment with moxonidine reproduced the beneficial effects on glucagon and lipids while the acute hyperglycemic response did not persist. Thus, alpha(2)-adrenergic receptors mediate an acute deterioration of glucose tolerance, whereas in contrast I(1)-imidazoline receptors appear to mediate the persistent long-term improvements in glucose tolerance. The therapeutic action of I(1)-imidazoline agonists may be primarily mediated through reduced glucagon secretion. |
Databáze: | OpenAIRE |
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