Liver and kidney metabolism during prolonged starvation

Owen, Oliver E.; Felig, Philip; Morgan, Alfred P.; Wahren, John; Cahill, George F.

doi:10.1172/jci106016

Cited by 803 publications

(413 citation statements)

References 30 publications

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“…However, they are removed by the human kidney in vivo in certain other pathological states. This was first demonstrated in patients with various renal diseases [2] and, later observed [3] in obese patients following prolonged starvation. Since most of our knowledge concerning the metabolism of lactate and pyruvate has been derived from arterio-venous measurements, the metabolic fate of these substrates in the human kidney remains uncertain.…”

Section: Introductionmentioning

confidence: 82%

“…This suggests that lactate may significantly contribute to the renal production of glucose, which occurs in patients with chronic obstructive airway diseases [IS] and in obese subjects undergoing prolonged starvation [3]. Glucose synthesis from lactate might appear to be of no importance in patients with renal diseases, because the kidneys of these patients do not release glucose [2].…”

Section: Time (Min)mentioning

confidence: 99%

“…Complete oxidation of lactate was calculated [2] to account for 35% of renal oxygen consumption. However, it was concluded [3] that all the lactate and pyruvate carbon skeletons removed by the kidney were converted to glucose.…”

Section: Introductionmentioning

confidence: 99%

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Lactate and pyruvate metabolism in isolated human kidney tubules

Baverel¹,

Bonnard²,

Pellet³

1979

FEBS Letters

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Section: Introductionmentioning

confidence: 82%

Section: Time (Min)mentioning

confidence: 99%

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Lactate and pyruvate metabolism in isolated human kidney tubules

Baverel¹,

Bonnard²,

Pellet³

1979

FEBS Letters

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“…Hepatic gluconeogenesis from amino acids (mainly alanine) is gradually replaced by renal gluconeogenesis. Under these conditions, glucose produced by the kidney can account for up to 50% of circulating plasma glucose (17).…”

Section: Glutamine/glutamate In the Kidneymentioning

confidence: 99%

Glutamine and glutamate as vital metabolites

Newsholme

Lima

Procópio

et al. 2003

Braz J Med Biol Res

318

225

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Glucose is widely accepted as the primary nutrient for the maintenance and promotion of cell function. This metabolite leads to production of ATP, NADPH and precursors for the synthesis of macromolecules such as nucleic acids and phospholipids. We propose that, in addition to glucose, the 5-carbon amino acids glutamine and glutamate should be considered to be equally important for maintenance and promotion of cell function. The functions of glutamine/glutamate are many, i.e., they are substrates for protein synthesis, anabolic precursors for muscle growth, they regulate acid-base balance in the kidney, they are substrates for ureagenesis in the liver and for hepatic and renal gluconeogenesis, they act as an oxidative fuel for the intestine and cells of the immune system, provide inter-organ nitrogen transport, and act as precursors of neurotransmitter synthesis, of nucleotide and nucleic acid synthesis and of glutathione production. Many of these functions are interrelated with glucose metabolism. The specialized aspects of glutamine/glutamate metabolism of different glutamineutilizing cells are discussed in the context of glucose requirements and cell function.

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“…Glucose is exogenously supplied from foods and endogenously produced from liver [7]. In diabetes, hepatic gluconeogenesis is constantly upregulated by insulin resistance or deficiency [1].…”

Section: Discussionmentioning

confidence: 99%

The Novel Gluconeogenesis Inhibitor FR225654 that Originates from Phoma sp. No. 00144

Ohtsu

Sasamura²,

Tanaka³

et al. 2005

J Antibiot

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FR225654, a novel gluconeogenesis inhibitor, was isolated from the culture broth of Phoma sp. No. 00144 and purified by adsorptive resin and reverse-phase column chromatography. This compound is a potent inhibitor of gluconeogenesis and is a promising candidate of anti-diabetic agent. Keywords gluconeogenesis, hepatocyte, diabetes, FR225654 IntroductionIt is estimated that there are about 7.4 million and 135 million patients of diabetes in Japan and in the world, respectively. The populations of diabetic patients are increasing accompanying with lack of exercise and excess of diet. In diabetes, the insulin resistance and/or deficiency causes a loss of glucose utilization in skeletal muscles and adipose tissues and an acceleration of glucose production in liver [1].Hepatic glucose production is brought by both of gluconeogenesis and glycogenolysis. The hyperproduction of glucose from liver in diabetes is based on a greater upregulation of the gluconeogenesis pathway compared with the glycogenolysis pathway [1]. Consequently, it is possible that inhibitors of gluconeogenesis are effective anti-diabetic drugs. To identify novel gluconeogenesis inhibitors, we used primary cultured rat hepatocytes to screen various microbial products for their ability to inhibit glucose production in vitro. During the course of this screening, we discovered a novel inhibitor named FR225654 (Fig. 1).FR225654 originated from the cultured broth of fungal strain No. 00144, which was isolated from a decayed leaf. This compound had potent inhibitory activity of gluconeogenesis in vitro and hypoglycemic activities in vivo. In this paper, we describe the taxonomy and the fermentation of fungal strain No. 00144 and the isolation

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Liver and kidney metabolism during prolonged starvation

Cited by 803 publications

References 30 publications

Lactate and pyruvate metabolism in isolated human kidney tubules

Lactate and pyruvate metabolism in isolated human kidney tubules

Glutamine and glutamate as vital metabolites

The Novel Gluconeogenesis Inhibitor FR225654 that Originates from Phoma sp. No. 00144

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