Insulin may boost breast milk supply

Scientists have found that the hormone insulin may play an important role in breast milk production, a finding that can help explain why many mothers have difficulty making enough milk to breastfeed.

Researchers  found insulin to be responsible for lactation success.

The study is the first to describe how the human mammary gland becomes highly sensitive to insulin during lactation. It is also the first study to get an accurate picture of how specific genes are switched on in the human mammary gland during lactation.

The researchers used next generation sequencing technology, RNA sequencing, to reveal "in exquisite detail" the blueprint for making milk in the human mammary gland, according to  author of the study.

For a long time, insulin was not thought to play a direct role in regulating the milk-making cells of the human breast, because insulin is not needed for these cells to take in sugars, such as glucose.

Scientists now, however, appreciate that insulin does more than facilitate uptake of sugars. This new study shows a dramatic switching on of the insulin receptor and its downstream signals during the breast's transition to a bio-factory that manufactures massive amounts of proteins, fats and carbohydrates for nourishing the newborn baby.

Researchers were able to use a non-invasive method to capture mammary gland RNA - a chain of

molecules that are blueprints for making specified proteins - in samples of human breast milk. They then created the first publicly accessible library of genes expressed in the mammary gland based on RNA-sequencing technology.

This approach revealed a highly sensitive portrait of the genes being expressed in human milk-making cells. They discovered an orchestrated switching on and off of various genes as the mammary gland transitions from secreting small amounts of immunity-boosting colostrum in the first days after giving birth to the copious production of milk in mature lactation.

In particular, the PTPRF gene, which is known to suppress intracellular signals that are usually triggered by insulin binding to its receptor on the cell surface, may serve as a bio-marker linking insulin resistance with insufficient milk supply.

Now that they've demonstrated the significance of insulin signalling in the human mammary gland, scientists are planning a phase I/II clinical trial with a drug used to control blood sugar in type 2 diabetes to determine whether it improves insulin action in the mammary gland, thus improving milk supply.

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exposure to social stress early in life ups breast cancer risk

Local chemical signals released by fat cells in the mammary gland appear to provide a crucial link between exposure to unrelenting social stressors early in life, and the subsequent development of breast cancer, according to researchers from the University of Chicago.

Some forms of stress exposure may be associated with an increased risk of certain types of aggressive breast cancer. But the mechanisms linking the biology of social stress to cancer have been hard to identify.

To unravel that mechanism, the researchers looked for differences between mice raised in small groups and those that grow up in an isolated setting-an established model of chronic stress without social supports.

"We found that exposure to the stress of social isolation leads to reprogramming of genes in fat cells in the mammary glands. These fat cells then secrete substances that cause nearby pre-cancerous epithelial cells to proliferate more rapidly, accelerating the development of breast cancer. This local effect of fat cells in the breast was completely unanticipated," said study author Suzanne Conzen, MD, professor of medicine at the University of Chicago.

The researchers used a genetically altered mouse model of "triple-negative" breast cancer-a form of the disease that lacks receptors for estrogen, progesterone and HER2, three important treatment targets in humans. Triple-negative cancer, representing about 15 percent of all breast cancers, appears to occur disproportionately in younger women. In this mouse model, animals develop precancerous changes in mammary epithelial cells that later lead to cancer.

The mice tested-known as SV40-T antigen mice-all develop tumors by about 16 weeks of age. The researchers previously showed that female mice raised in isolation develop significantly larger, more aggressive, triple negative tumors, and wanted to understand the detailed biology underlying this observation.

Conzen worked closely with colleague Martha McClintock, PhD, professor of psychology at the University of Chicago, to carefully model chronic social stress exposure in female mice. In previous joint projects they showed that a measurable chronic stress response could reliably be induced in mice by raising them in isolation after weaning, rather than housing them in small groups.

In this study, Conzen also worked with colleague, Matthew Brady, PhD, associate professor of medicine and a specialist in fat cell biology, to decipher the effect of stress on the mammary fat.

The researchers looked for differences in gene expression in multiple tissues and circulating hormones between group-housed and isolated mice. To their surprise, there were no significant differences in circulating hormones.

They found a dramatic change, however, in fat cells located within mammary glands. Measurements of those cells taken at 15 weeks of age showed that social isolation stimulated significant increases in the expression of three genes-Hk2 (hexokinase), Acly (ATP citrate lyase) and Acaca (acetyl-CoA carboxykase).

Why is breast fat particularly sensitive to the effects of social isolation? Scientists don`t yet understand how this response fits into the larger picture of the deleterious effects of stress on an organism, but "it will be an important avenue to pursue, particularly when so much human disease appears to be negatively impacted by social stress, diet, and other factors causing metabolic derangement," Conzen said.




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