Robert L. Jungas

Hormonal regulation of pyruvate dehydrogenase.

Abstract Studies of fatty acid synthesis in rat epididymal adipose tissue have revealed that insulin accelerates the conversion of medium lactate or pyruvate or of endogenous glycogen to fatty acids. These effects appear to result from an increased conversion of pyruvate to CO2 and acetyl CoA in the presence of the hormone. The activity of pyruvate dehydrogenase was measured in homogenates and found to be greater in homogenates prepared from tissue exposed to insulin prior to homogenization. Exposure of the tissue to epinephrine for 5 or 10 minutes prior to homogenization resulted in a diminished pyruvate dehydrogenase activity whereas exposure for a period of 30 minutes or longer led to enhanced activity. This enhancement was not seen when insulin was present in addition to epinephrine. It is suggested that the pyruvate dehydrogenase activity of adipose tissue is subject to regulatory influences that can be modified by the hormones insulin and epinephrine.

Regulation of lipogenesis in adipose tissue: The significance of the activation of pyruvate dehydrogenase by insulin

Abstract Simultaneous measurements were made of lipogenesis and pyruvate dehydrogenase activity in segments of rat epididymal adipose tissue incubated with saturating amounts of [U- 14 C]glucose and insulin. Glucose was converted to fatty acids at a rate only 64–79% of that permitted by the tissues content of the active form of pyruvate dehydrogenase (PDH a ). Addition of either of the electron acceptors, phenazine methosulfate (10 μ m ) or N,N,N′,N′ -tetramethyl- p -phenylenediamine (50 μ m ), increased lipogenesis until it equalled the PDH a activity of the tissue. Pyruvate release was increased 2-fold or more by the electron acceptors, suggesting that the increase in lipogenesis might have resulted from an increase in the intracellular pyruvate levels such that PDH a became saturated with substrate. Higher levels of the electron acceptors decreased PDH a activity, and reduced lipogenesis correspondingly. The data suggest that the maximal rate of lipogenesis in the presence of glucose and insulin is limited by the inability of the tissue to elevate pyruvate levels sufficiently to saturate PDH a . Although glycerol release was increased by either electron acceptor and insulin partially overcame this effect, the effects of the electron acceptors on PDH a activity could not be attributed to an increase in lipolysis.

Studies on the metabolism of adipose tissue. VII. A comparison of the effects of insulin and a growth-hormone preparation on oxygen consumption in bicarbonate and phosphate buffers.

Abstract Simultaneous measurements of the oxygen consumption of rat epididymal adipose tissue in Krebs-Ringer bicarbonate and phosphate buffers have been made using the Warburg reprirometer and a specially-constructed oxygen-electrode apparatus. Experiments performed by incubating one tissue in phosphate buffer in a Warburg vessel and a paired tissue from the same animal in bicarbonate buffer in the electrode tissue chamber have indicated that the oxygen uptake of the untreated tissue is not affected by the buffer composition. Glucose, 3 mg/ml, was employed in both media. When a sheep growth-hormone preparation was added to the incubation media so as to give a final concentration of 0.093 mg/ml the oxygen consumption of the tissue was approximately doubled irrespective of the buffer employed. The addition of insulin (0.1 unit/ml), however, produced a stimulation of oxygen uptake only in bicarbonate buffer and this effect was dependent upon the presence of glucose in the medium. When both hormones (growth-hormone preparation, 0.045 mg/ml; insulin, 0.1 unit/ml) were added simultaneously, the response of the tissue was much larger than when only the growth-hormone preparation was added, although the response remained the same in each buffer.

Similar and opposite effects of dibutyryl cyclic AMP and insulin on glucose metabolism in adipose tissue

Abstract The effects of N6-2′-O-dibutyryl cyclic AMP on glucose metabolism and lipolysis in fragments of rat epididymal adipose tissue were studied. Measurements were made of glucose uptake, conversion of glucose carbon to CO2 and tissue fatty acids and glyceride-glycerol, lactate production, and glycerol release. Low concentrations of dibutyryl cyclic AMP (0.1–0.5 mM) increased all parameters of glucose metabolism and inhibited glycerol release in tissue from both normally fed and fasted rats. Higher concentrations of dibutyryl cyclic AMP (3–5 mM) diminished glucose utilization and greatly accelerated lipolysis. Insulin, 50 μunits/ml, accelerated glucose metabolism in the presence of either low or high concentrations of dibutyryl cyclic AMP though the effect of insulin was greatly reduced by 3 mM dibutyryl cyclic AMP. Tissue exposed to concentrations of dibutyryl cyclic AMP which inhibited glucose metabolism (5 mM), then rinsed and reincubated without dibutyryl cyclic AMP, displayed increased glucose utilization. The results of these experiments emphasize the need for caution in interpretation of the effects of dibutyryl cyclic AMP on adipose tissue metabolism and the need for further research to elucidate the role of cyclic AMP in the regulation of glucose metabolism.