Effects of intrabrachial arterial infusion of pyruvate on forearm tissue metabolism

Pozefsky, Thomas; Tancredi, Robert G.

doi:10.1172/jci107048

Cited by 37 publications

(8 citation statements)

References 37 publications

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“…When concentrations of lactate or pyruvate were raised by their intravenous infusion or exercise, uptake of these metabolites by skeletal muscle ensued in the forearm (93)(94)(95), leg (96), and rat hindlimb (97), and in the latter the uptake was proportional to the rise in concentrations.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Metformin Action in Non-Insulin-Dependent Diabetes

et al. 1987

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The mechanism of action of metformin was studied by comparing glucose turnover before and after a 75-g oral glucose load in 10 nonobese men with non-insulin-dependent diabetes mellitus (NIDDM) during metformin and placebo therapy by the combined application of the forearm and double-isotope techniques. During the study, 9 of the 10 patients were regularly receiving glibenclamide therapy. In 5 of the men, the first study was performed during metformin therapy, and the second study was done during placebo administration; in the other 5 subjects, the order was reversed. The interval between the studies was at least 3 mo. The metformin dosage was 1 g twice daily in 9 of the patients and 850 mg thrice daily in the 10th subject. In the basal state, metformin administration reduced plasma glucose levels from 172 +/- 14 to 103 +/- 9 mg/dl (P less than .005), hepatic glucose output (HGO) from 2.67 +/- 0.15 to 2.20 +/- 0.20 mg X kg-1 X min-1 (P less than .02), and forearm glucose uptake (FGU) from 0.106 +/- 0.18 to 0.039 +/- 0.016 mg X 100 ml-1 forearm X min-1 (P less than .005), whereas insulin (23 +/- 6 microU/ml) and lactate (1.56 +/- 0.18 mM) levels were unchanged. Although the oral glucose tolerance curve (OGTC) was significantly lowered by metformin, the incremental area under the curve and the insulin response were unchanged. The systemic appearance of ingested glucose was unaffected by metformin; 64 +/- 2% of the load was recovered peripherally in 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

Mechanism of Metformin Action in Non-Insulin-Dependent Diabetes

et al. 1987

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“…This finding is in agreement with the report of Rabin et al [47], showing a decrease in alanine splanchnic uptake in normal subjects after infusion of somatostatin plus insulin in order to obtain a selective glucagon deficiency. The greater insulin sensitivity of pancreatogenic diabetic patients can also lead to an exaggerated pyruvate production with subsequently increased alanine synthesis through aminotransferase [48].…”

Section: Discussionmentioning

confidence: 99%

Effect of insulin replacement on intermediary metabolism in diabetes secondary to pancreatectomy

et al. 1983

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Patients with diabetes due to pancreatectomy have metabolic features different from Type 1 (insulin-dependent) diabetes after insulin withdrawal. Whether or not glucagon by itself or combined glucagon-insulin absence are responsible for this metabolic behaviour is unknown. This study was carried out to evaluate the ability of insulin replacement to abolish differences between patients with Type 1 diabetes and patients with diabetes due to pancreatectomy. We studied the diurnal patterns of intermediary metabolites, free insulin, and glucagon using the Biostator (glucose-controlled insulin infusion system) and intensive subcutaneous insulin therapy in five patients after total pancreatectomy, five after partial pancreatectomy and seven patients with Type 1 diabetes. All were studied for 24 h after an overnight period of normoglycaemia. Insulin requirement was lower in the patients with total pancreatectomy than in patients with partial pancreatectomy or Type 1 diabetes during both types of insulin treatment (p less than 0.05). Blood glucose and free insulin were similar in all the groups in both conditions. Immunoreactive glucagon was higher in the patients with diabetes secondary to pancreatectomy than in Type 1 diabetic patients. However, glucagon levels did not increase after arginine infusion in the patients with total pancreatectomy, and column chromatography of blood samples from two totally pancreatectomized patients showed no significant levels of immunoreactive pancreatic glucagon. Non-esterified fatty acids and ketone bodies were similar during Biostator and intensive subcutaneous insulin therapy. By contrast, gluconeogenic precursors (lactate, pyruvate, alanine and glycerol) were higher in patients with total pancreatectomy than in patients with partial pancreatectomy and Type 1 diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…alanine and glutamine, from the peripheral tissues, primarily muscles, is an important factor in the regulation of gluconeogenesis (Felig et al, 1969;Pozefsky & Tancredi, 1972). Stimulation of branched-chain amino acid oxidation by muscles in conditions of stress and carbohydrate deprivation may serve a dual role: the carbon skeleton is used as fuel for muscles, and the amino group becomes available for the formation of alanine and glutamine, substrates for gluconeogenesis by liver and kidney.…”

Section: Discussionmentioning

confidence: 99%

Regulation of branched-chain amino acid oxidation in isolated muscles, nerves and aortas of rats

Buse¹,

Jursinic²,

Reid³

1975

Biochemical Journal

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1. The oxidation of the three branched-chain amino acids was regulated in parallel fashion in rat tissues studied in vitro. 2. With 0.1 mM-[1-14C]isoleucine as substrate in the presence of 5.5 mM-glucose, 14CO2 production was 0.6 mumol/2 h per g in the aorta, 0.3 in peripheral nerve, 0.2 in muscle and 0.13 in spinal cord. 3. The ratio 14C oxidized/14C incorporated into proteins with 0.1 mM-[1-14C]leucine was 1.3 in hemidiaphragms, 3.3 in sciatic nerve and 1.0 in nerves undergoing Wallerian degeneration. Leucine oxidation decreased only slightly during degeneration, but protein synthesis doubled. 4. Hemidiaphragms incubated with [1-14C]leucine or 4-methyl-2-oxo[1-14C]pentanoate increased 14CO2 production 7-9-fold as substrate concentration was increased from 0.1 to 0.5 mM; under the same conditions 14CO2 production by nerves increased only 2-3-fold. 5. 2-Oxoglutarate stimulated the oxidation of the branched-chain amino acids by muscles and peripheral nerves and the oxidation of 4-methyl-2-oxopentanoate by hemidiaphragms but not by nerves. 6. Octanoate (0.1-1.0 mM) markedly stimulated the oxidation of branched-chain amino acids and of 4-methyl-2-oxopentanoate in hemidiaphragms, but inhibited oxidation of both by peripheral nerves and spinal cord. In aortas, oxidation of isoleucine (the only substance tested) was inhibited by octanoate. 7. The effects of octanoate and 2-oxoglutarate on leucine oxidation by hemidiaphragms were additive at low concentrations. When maximally stimulating concentrations of either agent were used, addition of the other was ineffective. 8. Pyruvate inhibited the oxidation of branched-chain amino acids and 4-methyl-2-oxopentanoate in all tissues tested. 9. Insulin did not affect the oxidation of 4-methyl-2-oxopentanoate by muscles or nerves. 10. The oxidative decarboxylation of the branched-chain alpha-oxo acids is suggested as a regulatory site of branched-chain amino acid oxidation. Differences in regulation between muscle on the one hand, and nerve and aorta on the other, are discussed.

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Effects of intrabrachial arterial infusion of pyruvate on forearm tissue metabolism

Cited by 37 publications

References 37 publications

Mechanism of Metformin Action in Non-Insulin-Dependent Diabetes

Mechanism of Metformin Action in Non-Insulin-Dependent Diabetes

Effect of insulin replacement on intermediary metabolism in diabetes secondary to pancreatectomy

Regulation of branched-chain amino acid oxidation in isolated muscles, nerves and aortas of rats

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