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

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 (14)C-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.

Association of a polymorphism in the 3' untranslated region of the <i>OLR1</i> gene with milk fat and protein in dairy cows

“…On the other hand, there is increasing evidence that Ox-LDL induces beta cell dysfunction and reduction of insulin production (Maziere et al 2004, Abderrahmani et al 2007, Favre et al 2011. Considering the role of insulin in stimulating protein synthesis in mammary gland (Mackle et al 2000, Molento et al 2002, Menzies et al 2009, Appuhamy et al 2011, it can be hypothesized that Ox-LDL may decrease protein synthesis by reducing insulin production in beta cells and its signalling in mammary cells. OLR1, as a major receptor for Ox-LDL, is able to remove Ox-LDL from circulating blood and as a result reduces its deleterious effect on insulin production and signalling.…”

Strategies for optimizing nitrogen use by ruminants

“…Knowledge to regulate gene expression and enzyme activity by nutritional management is still scarce, although some interesting results have been observed recently. Menzies et al (2009) studied the effect of insulin on gene expression in mammary explants prepared from pregnant non-lactating dairy cows. In combination with hydrocortisone and prolactin, including insulin in the medium resulted in the upregulation of genes involved in the synthesis of milk proteins and lactoferrin.…”

Gene expression of six major milk proteins in primary bovine mammary epithelial cells isolated from milk during the first twenty weeks of lactation

“…Furthermore, milk protein synthesis may be regulated at multiple levels within the mammary epithelial cells including transcription, post-transcription, translation, and amino acid supply (Menzies et al, 2009). The genes encoding these proteins are regulated by the complex interplay of peptide and steroid hormones, predominantly the lactogenic hormones prolactin, insulin, and hydrocortisone, and cell-cell and cell-substratum interactions.…”

“…In this context, many signalling pathways in the lactating pBMEC are known, i.e. the janus kinase/signal transducer and activator of transcription cascade (Darnell, 1997), the growth hormone effects in the mammary mammalian target of rapamycin signalling pathway (Cui et al, 2003), the interaction of insulin and the major milk protein transcription factor E74-like factor 5 (Menzies et al, 2009), and the amino acids and glucose transporters (Zhao et al, 1996(Zhao et al, , 2005. Future research in that field could provide valuable information on improved lactation performance of dairy cows.…”