Search

Glucose turnover, glycerol turnover, and the rate of incorporation of glycerol carbon into glucose were measured with the tracer technique (primed constant rate infusion) using 2-3H-glucose and 14C-glycerol, at rest and during exercise (treadmill run) in normal (N), alloxan-diabetic (D), and methylprednisolone treated diabetic (MPD) dogs. At rest only 2%-3% of the hepatic glucose output arose from glycerol. Exercise increased gluconeogenesis about ninefold in N dogs and about fourfold in D and MPD animals, yet less than 9% of the elevated glucose turnover was derived from glycerol. There was a direct linear correlation between the rates of glycerol turnover and gluconeogenesis from glycerol at rest and during exercise in all three groups. The slope constants were however significantly different: 0.45, 0.51, and 0.67 for N, D, and MPD dogs, respectively. In vivo the major factor controlling the rate of gluconeogenesis from glycerol seems to be the glycerol supply on which the specific effects of insulin deficiency and glucocorticoid treatment are superimposed. They appear to be of minor importance. A comparison of the glucose turnover measured by 2-3H-glucose with that measured by 6-3H-glucose showed that the activity of the glucose in equilibrium glucose-6-P cycle was threefold higher in D dogs and elevated by 15-fold in MPD animals.

The rates of appearance of FFA (RaFFA) and that of glycerol (RaGLY) were measured simultaneously with [1-14 C]palmitate and [2-3H]-glycerol, in dogs with indwelling arterial and venous catheters. Lipolysis was stimulated by exercise (treadmill run on 10% slope) or by the infusion of norepinephrine (0.5 mug/kg-min). Na-L(+)-lactate (L), Na-pyruvate (Py), or Na-nicotinate (N) were infused. All three components decreased RaFFA. RaGLY was increased by L, unaltered by Py, and decreased by N. There was an inverse correlation (P less than 0.001) between the logarithms of RaFFA and plasma lactate. A linear correlation was obtained between RaGLY and plasma lactate when this latter was increased by the infusion of L. It is suggested that a) lactate in physiological concentrations inhibits the release of FFA stimulated by exercise and b) the increase of the NADH/NAD ratio leads to the formation of alpha-glycerophosphate which in turn yields glycerol. Therefore changes in plasma glycerol do not reflect lipolysis when blood lactate increases. c) The effect of lactate on RaFFA can be explained by an enhanced reesterification, although a direct inhibition on lipase could not be excluded.

The effect of treadmill run on the turnover rates of glucose ([2-3H]glucose) and lactate ([U-14C]lactate), on the rates of oxidation (ROX) of lactate, and its conversion to glucose (L LEADS TO G) were measured with the primed constant-infusion technique. Comparable lactate turnover rates were obtained at rest by infusing epinephrine, or Na-L(+)-lactate with or without norepinephrine. With increasing lactate levels (L) the rate of disappearance (RdL), ROX, and L leads to G increase in a linear manner. At the same lactate level, RdL, ROX, and L leads to G are significantly higher in the running dog. Exercise increased the metabolic clearance rate of lactate threefold. At rest ROX and L leads to G represented about 50% and 18-19% of RdL, respectively. The corresponding values in the running dogs were 55% and 25%, respectively. At rest about 9% of the hepatic glucose output arose from lactate while during exercise this varied from 7 to 26% depending on RdL. It is concluded that a) the working muscle produces and utilizes lactate at the same time, and b) "in vivo" the major factor which controls both ROX and gluconeogenesis is the substrate supply.

Dogs with indwelling arterial and venous catheters ran on a treadmill on a 10% or on a 15% slope at 100 m/min. Glycerol turnover ([2-3H]-glycerol) and FFA turnover ([1-14C]palmitate) were measured simultaneously. Both turnovers were greatly increased by exercise. Similar increases were produced in resting dogs by norepinephrine infusions (0.5 mug/kg-min). At rest, as well as during exercise, there was a straight-line correlation between the ratio of disappearance of each substrate and their respective plasma concentrations. Over a wide range there was a straight-line correlation between the rate of production of FFA (RaFFA) and that of glycerol (RaGLY) at rest as well as during exercise. At any given RaFFA, RaGLY was higher in the running than in the resting dog. At rest the ratio of RaFFA/RaGLY was found to give the theoretical value of 3.0 only when RaFFA was 10-15 mumol/kg-min, below this the ratio was lower and above this it was higher. During exercise the ratio was lower than at rest and at heavier load lower than at lighter work. The results suggest that in vivo a combination of partial and complete lipolysis as well as reesterification occurs. The glucose equivalent of the glycerol turnover (if 100% converted) represents (under the given experimental conditions) 14-18% of the hepatic glucose output on the 15% slope and 20-25% of it on the 10% slope.

Dogs with indwelling polyethylene arterial and venous catheters ran on a treadmill (slope 15 per cent, speed 100 m./min.). Diabetes was produced by alloxan or by a combination of alloxan and streptozotocin. Glucose turnover was measured according to the primed constant-rate infusion technics with 2-3H-glucose as tracer. In resting diabetic dogs plasma glucose varied between 200 and 650 mg./100 ml. There was a direct linear correlation between the hepatic glucose output (Ra) and the plasma glucose level. Exercise increased both Ra and the clearance rate (CR) of glucose; however, Ra could not match the rate of disappearance (=renal loss plus glucose uptake of the muscle), causing the plasma glucose to decline more rapidly than in the running control dogs. Two to three days' treatment with methylprednisolone (MP, 3-3.2 mg./kg./day) caused a higher resting glucose level and a higher Ra. Exercise greatly increased the plasma glucose concentration, partly because MP enhanced the hepatic response but mainly because it essentially prevented the rise of CR. It is concluded that (a) in chemically induced diabetes, the variable glucose level is the result of a variable rate of hepatic glucose output; (b) the increase of Ra by MP treatment does not increase the plasma glucose in the normal dog but significantly aggravates the alloxan diabetes, (c) diabetes reduces the effect of exercise on the glucose uptake of the muscle, and this effect is potentiated by the inhibitory action of the glucocorticoid. This latter becomes unmasked only when the insulin secretion is impaired.