Role of the sulfonylurea receptor in regulating human adipocyte metabolism

A regulatory role for intracellular Ca2+ ([Ca2+](i)) in adipocyte lipogenes is, lipolysis and triglyceride accumulation has been demonstrated. Compound s acting on the pancreatic sulfonylurea receptor (SUR) to increase (e.g., g libenclamide) or decrease (e.g., diazoxide) [Ca2+](i) cause corresponding i ncreases and decreases in weight gain. However, these weight gain and loss effects have been attributed to insulin release rather than to the primary effects of these compounds on the adipocyte SUR and its associated K-ATP ch annel, Accordingly, we have evaluated the direct role of the human adipocyt e SUR in regulating adipocyte metabolism. We used RT-PCR with primers for a highly conserved region of SUR1 to demonstrate that human adipocytes expre ss SUR1. The PCR product was confirmed by sequence analysis and used as a p robe to demonstrate adipocyte SUR1 expression by Northern blot analysis, Ad ipocytes exhibited glibenclamide dose-responsive (0-20 mM) increases in [Ca 2+](i) (P<0.05). Similarly, glibenclamide (10 mM) caused a 67% increase in adipocyte fatty acid synthase activity (P<0.001), a 48% increase in glycero l-3-phosphate dehydrogenase activity (P<0.01) and a 68% inhibition in lipol ysis (P<0.01), whereas diazoxide (10 mM) completely prevented each of these effects, These data demonstrate that human adipocytes express a SUR that r egulates [Ca2+](i) and, consequently, exerts coordinate control over lipoge nesis and lipolysis. Accordingly, the adipocyte SUR1 may represent an impor tant target for the development of therapeutic interventions in obesity.