ALPHA2 ADRENERGIC RECEPTOR DYSFUNCTION IN PATIENTS WITH REGIONAL LIPOATROPHY

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Partial or total lipoatrophy is characterized by insulin resistant diabetes, hypertiglyceridemia, fatty infiltration of the liver, and hypertension. The etiology of this syndrome is unknown. The alpha2 adrenergic receptor is a Gi-dependent system which normally antagonizes the lipolytic effects of beta adrenergic agonists primarily in peripheral fat depots and antagonizes alpha1 adrenergic effects on vascular resistance. A defective alpha2 adrenergic receptor would likely result in accelerated lipolysis in peripheral fat depots thus resulting in a disappearance of fat in these regions and favoring accumulation in visceral and trunk depots. Such a defect would also tend to increase blood pressure. We propse to evaluate the function of the alpha2 adrenergic receptor in subjects with regional lipoatrophy by in vivo testing of the response to alpha2 adrenergic receptor agonists and antagonists and we will sequence the structural gene for the alpha2 adrenergic receptor in these patients.