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T T Aoki

Publications and source records attributed to T T Aoki.

At least 91 records · Page 5Linked to original sources

Ketosis.

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Acidosis↗

Effect of insulin on muscle glutamate uptake. Whole blood versus plasma glutamate analysis.

For decades, investigators concerned with protein metabolism in man have performed detailed amino acid analyses of human plasma obtained under a wide range of experimental situations. A large body of information has been used to calculated rates of protein synthesis and proteolysis. During the course of an investigation of the effect of intrabrachial artery infusion of insulin (70 muU/min per kg body weight) on glutamate uptake by human forearm muscle, it was discovered that plasma arterio-deep venous glutamate difference analysis failed to document any increase in the uptake of this amino acid, suggesting that insulin had little influence on glutamate uptake by muscle. However, whole blood glutamate analyses, performed on the same blood samples, revealed that (a) the resting muscle uptake of glutamate is smaller than previously reported and (b) insulin is capable of markedly increasing glutamate uptake by muscle from whole blood. Since the hematocrit was obtained on all samples, detailed analyses of the various compartments in which glutamate could be found were performed. It was determined that circulating blood cells have a dynamic role in glutamate transport. These data underscore the need for both whole blood and plasma amino acid analysis in investigations concerned with protein synthesis and/or amino acid flux, for analysis of plasma samples alone could be misleading as illustrated in the present study.

Blood Cells↗

Muscle and splanchnic glutmine and glutamate metabolism in postabsorptive andstarved man.

Arterio-venous differences across forearm muscle in man in both prolonged starvation and in the postabsorptive state, show an uptake of glutamate and a relatively greater production of glutamine. Splanchnic arteriovenous differences in the postabsorptive state show a net uptake of glutamine and lesser rate of glutamate production. These data suggest that muscle is a major site of glutamine synthesis in man, and that the splanchnic bed is a site of its removal. The relative roles of liver and other tissues in the splanchnic circuit were not directly assessed, only the net balance. These data in man are in conflict with most previous studies in other species attributing the major proportion of glutamine production to the liver and, pari passu, to the splanchnic bed.

Abdomen↗

Glucagon levels and metabolic effects in fasting man.

The role of glucagon in the metabolic adaptation to prolonged fasting in man has been examined. Plasma immunoreactive glucagon was determined during 6-wk fasts and during infusion of exogenous glucagon using an assay which minimized nonpancreatic immunoreactivity. Plasma glucagon concentrations rose twofold to a peak on the 3rd day of fasting and then declined thereafter to a level maintained at or above postabsorptive. Insulin concentration declined to a plateau by the 3rd day. Thus a persisting altered relationship of glucagon and insulin concentrations characterized the fasted state. A synergism of low insulin and relative or absolute elevation of glucagon levels is viewed as a hormonal mechanism controlling the rate of hepatic substrate extraction for gluconeogenesis. Glucagon was infused systemically into 4-6 wk fasted subjects at three dose levels. A marked sensitivity of individual plasma free amino acids to the induced elevations of plasma glucagon within the physiologic range was demonstrated. At higher concentrations, equivalent to those present in the portal vein, stimulation of hepatic gluconeogenesis occurred, and the effects on glucose, insulin, and growth hormone levels and on ketone metabolism were induced.

Adult↗

Hormone-fuel metabolism during exercise of insulin-dependent diabetic patients treated with an artificial B-cell unit.

The effects of restoration of glucose homeostasis on hormone-fuel metabolism of diabetic individuals during exercise (40% maximal O2 consumption) were determined by monitoring fuel oxidation rates and levels of substrates and hormones in nine normal subjects and five insulin-dependent diabetic patients while on conventional insulin therapy and after 3 days on artificial B-cell directed glucose regulation. The non-protein respiratory quotient (npRQ) and carbohydrate oxidation rate of the conventionally-treated diabetic subjects (0.908 +/- 0.002 and 538 +/- 5 mg/m2.min) were lower and the lipid oxidation rate (101 +/- 2 mg/m2.min) was significantly higher than those of the normal group during the bicycle exercise (101 +/- 2 mg/m2.min) was significantly 70 +/- 4 mg/m2.min, respectively). After 3 days of artificial B-cell insulin therapy, the npRQ and carbohydrate oxidation rate of the exercising diabetics significantly increased to 0.965 +/- 0.004 and 693 +/- 13 mg/m2.min, while the lipid oxidation rate declined to 39 +/- 4 mg/m2.min (p less than 0.001). We conclude that artificial B-cell directed insulin therapy increases carbohydrate oxidation and decreases lipid oxidation in exercising insulin-dependent diabetic subjects. However, if restoration of metabolic response identical to that of exercising normals is desired, the excess in carbohydrate oxidation coincident with elevated blood lactate and pyruvate levels suggest that the artificial B-cell therapy may not have been completely optimal, probably due to the hyperinsulinization of the diabetic patients.

Adult↗

Artificial beta-cell promotes positive nitrogen balance and whole body protein synthesis in insulin-dependent diabetic subjects.

To assess the effects of artificial beta-cell-directed insulin therapy on protein metabolism in patients with diabetes mellitus, nitrogen balance, urea production, and whole body protein turnover were determined in five type I insulin-dependent subjects and five age- and sex-matched controls. Each diabetic participant was studied over two 4-day periods while receiving conventional insulin therapy (one or two daily injections of short and intermediate acting insulin) or insulin delivered by the artificial beta-cell. While the diabetic participants received conventional insulin therapy, nitrogen balance, urea production, whole body protein turnover, and protein synthesis and breakdown rates did not differ significantly from the control group. However, when the same subjects were on artificial beta-cell-directed insulin therapy, they manifested a significant net positive nitrogen balance of over 2 g/day. This change in nitrogen balance was largely due to a fall in urea nitrogen production from 174 +/- 6 to 140 +/- 13 mg/kg body weight per day (p less than 0.05). In addition, while artificial beta-cell therapy did not affect whole body protein turnover or breakdown rates, a significant rise (2.1 +/- 0.2 to 2.4 +/- 0.1 g/kg per day) in whole body protein synthesis was observed (p less than 0.05). Thus when compared to conventional insulin treatment, artificial beta-cell-directed insulin therapy was associated with a 14% increase in the rate of protein synthesis and a decrease of 20% in urea nitrogen production, leading to a net positive nitrogen balance.

Adult↗