Glucagon and Amino Acid Metabolism

Cahill, George F.; Aoki, Thomas T.; Smith, Richard J.

doi:10.1007/978-3-642-68866-9_18

Cited by 2 publications

(2 citation statements)

References 95 publications

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“…Therefore, this change is considered to be of no toxicological significance. The cause of the increase in plasma albumin concentration, also seen in rats only, is uncertain but might reflect the anabolic effect of glucagon in the presence of insulin (Cahill et al 1983). Glucagon is known to increase renal blood flow and glomerular filtration rate, among other effects, resulting in increased excretion of water.…”

Section: Discussionmentioning

confidence: 99%

Glucagon Produced by Recombinant DNA Technology: Repeated Dose Toxicity Studies, Intravenous Administration to CD Rats and Beagle Dogs for Four Weeks

Eistrup

Hjortkjæ

Pickersgill³

et al. 1993

Pharmacology & Toxicology

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The toxicity of glucagon produced by recombinant DNA technology (Glucagon (ge)) was studied by daily intravenous administration to rats and dogs for 4 weeks. Pancreatic glucagon of bovine or porcine origin (Glucagon Novo) was used as a reference control in the dogs. Glucagon (ge) has the same sequence of the 29 amino acids as pancreatic glucagon of humans, cows, pigs, rats and dogs. The dosages were 0 (control), 0.2, 1.0 and 5.0 mg Glucagon (ge)/kg/day in the rats, and 0 (control), 1.0 and 5.0 mg Glucagon (ge) and 5.0 mg Glucagon (Novo)/kg/day in the dogs. The studies complied with current EEC, US and Japanese guidelines for 4 week toxicity studies of drugs. All dose levels were well tolerated. The plasma glucose and cardiovascular responses to dosing were monitored in the dogs and found to be in agreement with well-known effects of pancreatic glucagon. The most consistent finding in both species was an increase in liver weight. This change was without concomitant pathological deviations in the other parameters examined. There were no differences in the reaction of dogs following treatment with Glucagon (ge) or Glucagon (Novo). A dose of 1 mg Glucagon (ge)/kg/day was regarded as a clear no-toxic-effect-level in both species.

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Section: Discussionmentioning

confidence: 99%

Glucagon Produced by Recombinant DNA Technology: Repeated Dose Toxicity Studies, Intravenous Administration to CD Rats and Beagle Dogs for Four Weeks

Eistrup

Hjortkjæ

Pickersgill³

et al. 1993

Pharmacology & Toxicology

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“…However, enzyme induction cannot occur sufficiently rapidly to account for the increased degradation of amino acids observed after a single protein load [6]. A short-term stimulation of hepatic catabolism has been associated with an increased secretion of glucagon [7]; glucagon rapidly activates several oxidative reactions and stimulates amino acid catabolism [8][9][10]. We therefore investigated the short-term effects of glucagon on the activities of enzymes involved in the degradation of lysine and on measured rates of lysine oxidation in isolated liver mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Regulation of oxidative degradation of l-lysine in rat liver mitochondria

Ścisłowski¹,

Foster²,

Fuller³

1994

Biochemical Journal

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The generation of 14CO2 from [1-14C]lysine by hepatic mitochondria through the saccharopine pathway is controlled by intramitochondrial concentrations of lysine, 2-oxoglutarate and NADPH. Mitochondria, isolated from rats pre-treated with glucagon, exhibited higher activities of L-lysine: 2-oxoglutarate reductase, saccharopine dehydrogenase and 2-aminoadipate aminotransferase. The flux through this pathway is stimulated in liver mitochondria after glucagon treatment. Multiple regulation of lysine oxidation in liver mitochondria confirms a complex mechanism of 'mitochondrial activation' by glucagon.

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Glucagon and Amino Acid Metabolism

Cited by 2 publications

References 95 publications

Glucagon Produced by Recombinant DNA Technology: Repeated Dose Toxicity Studies, Intravenous Administration to CD Rats and Beagle Dogs for Four Weeks

Glucagon Produced by Recombinant DNA Technology: Repeated Dose Toxicity Studies, Intravenous Administration to CD Rats and Beagle Dogs for Four Weeks

Regulation of oxidative degradation of l-lysine in rat liver mitochondria

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