Examination of altered sympathetic nervous function in obesity and diabetes mellitus using [carbon-11]meta-hydroxyephedrine

Abstract

Abnormal sympathetic nervous system (SNS) signaling is a synergistic complication of obesity, diabetes mellitus, and congestive heart failure. In vivo biodistribution studies in rats using [11C] meta-hydroxyephedrine ([11C]HED) were performed in obese, lean, type I and type II diabetic animals to delineate deviations in sympathetic nervous integrity at the uptake-1 site (NET-1) as compared to healthy controls. Specific, blockable tracer accumulation was observed in myocardium, lung, brown adipose tissue and pancreas. Obese animals exhibit a time-dependent elevation in uptake-1 specific myocardial [11C]HED retention and time-independent depressed tracer accumulation in brown adipose tissue as compared to lean animals. Type II diabetic rats show a time- and hyperglycaemia-dependent reduction of myocardial tracer uptake and a time- and glycaemia-independent increase in brown adipose tissue uptake-1 specific [11C]HED retention. Positron emission tomography using [11C]HED may prove useful in examining alterations in SNS signaling before, during, and subsequent to therapy for obesity and/or DM.