Persson, M.

To determine the relationship between glycerol and nonesterified fatty acid (NEFA) release from adipose tissue, and to test whether forearm muscle and abdominal adipose tissue are capable of extracting these two lipolytic products from the circulation, 13 male subjects were studied after an overnight fast during combined infusion of radiolabeled palmitate and glycerol. Blood samples were taken from a radial artery, a deep forearm vein, and a superficial abdominal vein before and during a 2-h infusion of glucose at ∼7 mg ⋅ kg−1⋅ min−1. The ratio of the appearance rates of total NEFA to glycerol was ∼3/1 during the baseline period but decreased to 1.3/1 during glucose infusion. There was significant extraction of both glycerol and NEFA by forearm muscle. In contrast, there was no apparent uptake of glycerol by adipose tissue. Adipose tissue NEFA uptake was undetectable during the baseline period but became significant during glucose infusion. These data indicate that there is very little to no in situ reesterification of NEFA in adipose tissue after an overnight fast. During glucose infusion, there was apparently a relative increase in the fraction of glycerol derived from the action of lipoprotein lipase and an increase in reesterification in situ.

Growth hormone (GH) excess stimulates lipolysis, but its role in the hierarchy of lipolysis regulation is not clear. We studied whether pulsatile GH delivery is required for its lipolytic effect. With use of the pancreatic clamp, eight subjects were randomized to three protocols: protocol A, GH deficiency; protocol B, constant GH infusion; protocol C, pulsatile GH delivery (same total GH as protocol B). Pulsatile GH was given in four consecutive bursts, with symmetric peak width (60 min), amplitude of 10.7 (men) and 15 (women) ng.kg-1.min-1, and peak width at half-height of 15 min. Palmitate flux (PF) was measured at baseline and in the last hour of each study with [3H]palmitate. GH (ng/ml) decreased from approximately 3.5 to 2.0 in protocol A (P < 0.05), it remained between 3.2 and 4.0 in protocol B (P < 0.05), but in protocol C it fluctuated between approximately 2.7 and approximately 5.0 (P < 0.05). Palmitate concentration (in mumol/l) was approximately 150 at baseline; it did not change in protocols A and B (137 +/- 17 and 136 +/- 12, respectively) but increased to 198 +/- 16 (P < 0.05) in protocol C. PF (mumol.kg-1.min-1) was approximately 2.7 at baseline and did not change in protocol B (2.4 +/- 0.2); it decreased to 2.2 +/- 0.1 in protocol A (P < 0.05); it increased to 3.1 +/- 0.3 (P < 0.05) in protocol C. These experiments provide evidence that pulsatile secretion of GH is required for its lipolytic effect.

To define the mechanism of insulin's anticatabolic action, the effects of three different dosages of insulin (0.25, 0.5, and 1.0 mU x kg(-1) x min(-1)) versus saline on protein dynamics across splanchnic and skeletal muscle (leg) beds were determined using stable isotopes of phenylalanine, tyrosine, and leucine in 24 healthy subjects. After an overnight fast, protein breakdown in muscle exceeded protein synthesis, causing a net release of amino acids from muscle bed, while in the splanchnic bed protein synthesis exceeded protein breakdown, resulting in a net uptake of these amino acids. Insulin decreased (P &lt; 0.003) muscle protein breakdown in a dose-dependent manner with no effect on muscle protein synthesis, thus decreasing the net amino acid release from the muscle bed. In contrast, insulin decreased protein synthesis (P &lt; 0.03) in the splanchnic region with no effect on protein breakdown, thereby decreasing the net uptake of the amino acids. In addition, insulin also decreased (P &lt; 0.001) leucine nitrogen flux substantially more than leucine carbon flux, indicating increased leucine transamination (an important biochemical process for nitrogen transfer between amino acids and across the organs), in a dose-dependent manner, with the magnitude of effect being greater on skeletal muscle than on the splanchnic bed. In conclusion, muscle is in a catabolic state in human subjects after an overnight fast and provides amino acids for synthesis of essential proteins in the splanchnic bed. Insulin achieves amino acid balance across splanchnic and skeletal muscle beds through its differential effects on protein dynamics in these tissue beds.