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Insulin regulates milk protein synthesis at multiple levels in the bovine mammary gland

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Abstract

The role of insulin in milk protein synthesis is unresolved in the bovine mammary gland. This study examined the potential role of insulin in the presence of two lactogenic hormones, hydrocortisone and prolactin, in milk protein synthesis. Insulin was shown to stimulate milk protein gene expression, casein synthesis and 14C-lysine uptake in mammary explants from late pregnant cows. A global assessment of changes in gene expression in mammary explants in response to insulin was undertaken using Affymetrix microarray. The resulting data provided insight into the molecular mechanisms stimulated by insulin and showed that the hormone stimulated the expression of 28 genes directly involved in protein synthesis. These genes included the milk protein transcription factor, ELF5, translation factors, the folate metabolism genes, FOLR1 and MTHFR, as well as several genes encoding enzymes involved in catabolism of essential amino acids and biosynthesis of non-essential amino acids. These data show that insulin is not only essential for milk protein gene expression, but stimulates milk protein synthesis at multiple levels within bovine mammary epithelial cells.

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Abbreviations

AA:

amino acid

EAA:

essential amino acid

NEAA:

non-essential amino acid

BCAA:

branched chain amino acid

HEC:

hyperinsulinemic-euglycemic clamp

I:

insulin

F:

hydrocortisone

P:

prolactin

NH:

no hormone

IPA:

ingenuity pathways analysis

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Acknowledgements

The work in this study was funded by Dairy Australia and the CRC for Innovative Dairy Products.

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Correspondence to Karensa K. Menzies.

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ESM 1

The fold changes in gene expression in this list were generated from the RMA normalised data sets of the Affymetrix microarray analysis of cultured bovine mammary explants. The genes were assigned to cellular function categories using information from NCBI Gene Entrez and manual searching of the literature using the NCBI Pubmed and Entrez gene databases (DOC 1.93 MB).

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Menzies, K.K., Lefèvre, C., Macmillan, K.L. et al. Insulin regulates milk protein synthesis at multiple levels in the bovine mammary gland. Funct Integr Genomics 9, 197–217 (2009). https://doi.org/10.1007/s10142-008-0103-x

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  • DOI: https://doi.org/10.1007/s10142-008-0103-x

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