Regulation of albumin synthesis by hormones and amino acids in primary cultures of rat hepatocytes

Hutson, Susan M.; Stinson-Fisher, C.; Shiman, Ross; Jefferson, Leonard S.

doi:10.1152/ajpendo.1987.252.3.e291

Cited by 59 publications

(44 citation statements)

References 30 publications

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“…Where studied, there was no evidence of enteropathy or excess protein loss in the stools or urine We speculate that endogenous albumin synthesis may be compromised in these patients due to reduced LARS activity. Albumin is very sensitive to amino acid depletion, particularly in the case of leucine, isoleucine and tryptophan (Hutson et al 1987). Leucine is one of the most abundant amino acids in albumin (Table S3).…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic characterisation of infantile liver failure syndrome type 1, due to recessive mutations in LARS

Casey

Slattery

Cotter

et al. 2015

J of Inher Metab Disea

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Summary BackgroundRecessive LARS mutations were recently reported to cause a novel syndrome, Infantile Liver Failure Syndrome Type 1 (ILFS1), in six Irish Travellers. We have since identified four additional patients, including one of Ashkenazi origin, representing the largest ILFS1 cohort to date. Our study aims to define the ILFS1 clinical phenotype to help guide diagnosis and patient management.

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Section: Discussionmentioning

confidence: 99%

Clinical and genetic characterisation of infantile liver failure syndrome type 1, due to recessive mutations in LARS

Casey

Slattery

Cotter

et al. 2015

J of Inher Metab Disea

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“…We began the present studies by investigating the influence of In and HC on GSH levels in cultured hepatocytes. We chose to examine these two hormones because of their known importance in regulation of numerous proteins and enzymes in hepatocytes (19)(20)(21)(22)(23)(24)(25)(26). We observed that the lowest doses of In and HC which increased GSH were in the known physiologic range ofeach hormone (27, 28).…”

Section: Discussionmentioning

confidence: 99%

Insulin and glucocorticoid dependence of hepatic gamma-glutamylcysteine synthetase and glutathione synthesis in the rat. Studies in cultured hepatocytes and in vivo.

Lu¹,

Ge²,

Kuhlenkamp³

et al. 1992

J. Clin. Invest.

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We reported that glucagon and phenylephrine decrease hepatocyte GSH by inhibiting -t-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in GSH synthesis (Lu, S. C., J. Kuhlenkamp, C. Garcia-Ruiz, and N. Kaplowitz. 1991. J. Clin. Invest. 88:260-269). In contrast, we have found that insulin (In, 1 jig/ml) and hydrocortisone (HC, 50 nM) increased GSH of cultured hepatocytes up to 50-70% (earliest significant change at 6 h) with either methionine or cystine alone as the sole sulfur amino acid in the medium. The effect of In occurred independent of glucose concentration in the medium. Changes in steady-state cellular cysteine levels, cell volume, GSH efilux, or expression of y-glutamyl transpeptidase were excluded as possible mechanisms. Both hormones are known to induce cystine/glutamate transport, but this was excluded as the predominant mechanism since the induction in cystine uptake required a lag period of > 6 h, and the increase in cell GSH still occurred when cystine uptake was blocked. Assay of GSH synthesis in extracts of detergent-treated cells revealed that In and HC increased the activity of GCS by 45-65% (earliest significant change at 4 h) but not GSH synthetase. In and HC treatment increased the V.. of GCS by 31-43% with no change in K,.Both the hormone-mediated increase in cell GSH and GCS activity were blocked with either cycloheximide or actinomycin D. Finally, when studied in vivo, streptozotocin-treated diabetic and adrenalectomized rats exhibited lower hepatic GSH levels and GCS activities than respective controls. Both of these abnormalities were prevented with hormone replacement. Thus, both in vitro and in vivo, In and glucocorticoids are required for normal expression of GCS. (J. Clin. Invest. 1992. 90:524-532.)

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“…In diabetes, the concentration of albumin in blood is decreased, and administration of insulin is required to prevent hypoalbuminemia (6,7). Early biochemical studies have shown that insulin stimulates albumin production in the liver by activating gene transcription (5)(6)(7)(8)(9)(10)(11)(12). However, the detailed pathway by which insulin exerts this effect has not been described.…”

mentioning

confidence: 99%

Insulin Is Required to Maintain Albumin Expression by Inhibiting Forkhead Box O1 Protein

Chen

Monks

et al. 2016

Journal of Biological Chemistry

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Diabetes is accompanied by dysregulation of glucose, lipid, and protein metabolism. In recent years, much effort has been spent on understanding how insulin regulates glucose and lipid metabolism, whereas the effect of insulin on protein metabolism has received less attention. In diabetes, hepatic production of serum albumin decreases, and it has been long established that insulin positively controls albumin gene expression. In this study, we used a genetic approach in mice to identify the mechanism by which insulin regulates albumin gene transcription. Albumin expression was decreased significantly in livers with insulin signaling disrupted by ablation of the insulin receptor or Akt. Concomitant deletion of Forkhead Box O1 (Foxo1) in these livers rescued the decreased albumin secretion. Furthermore, activation of Foxo1 in the liver is sufficient to suppress albumin expression. These results suggest that Foxo1 acts as a repressor of albumin expression.

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Regulation of albumin synthesis by hormones and amino acids in primary cultures of rat hepatocytes

Cited by 59 publications

References 30 publications

Clinical and genetic characterisation of infantile liver failure syndrome type 1, due to recessive mutations in LARS

Clinical and genetic characterisation of infantile liver failure syndrome type 1, due to recessive mutations in LARS

Insulin and glucocorticoid dependence of hepatic gamma-glutamylcysteine synthetase and glutathione synthesis in the rat. Studies in cultured hepatocytes and in vivo.

Insulin Is Required to Maintain Albumin Expression by Inhibiting Forkhead Box O1 Protein

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