Infertility Caused by Insulin Sensitivity

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The inability to conceive is common to women with reproductive system disorder, may it be genetically-linked or not. However, the infertility caused by obesity in women is not yet clearly been known if what is the real cause of it. In a report, published online Nov.10 in the journal Diabetes, the Johns Hopkins scientists say the real culprit appears to be insulin sensitivity in the ovaries and the pituitary.

A team of Johns Hopkins Children’s Center scientists, conducting experiments in mice, has uncovered what they consider surprising evidence that insulin resistance, long considered a prime suspect, has little to do with infertility in women with type-2 diabetes (inability to use glucose in the blood), polycystic ovary syndrome (PCOS) (an endocrine rerated disorder characterized by anovulation) and metabolic syndrome, all obesity-related conditions in which the body becomes desensitized to insulin and loses the ability to regulate blood sugar.

The Johns Hopkins team concluded that the ovaries and the pituitary escape insulin resistance.The high levels of insulin common in obese patients and, develops abnormal cell signaling that disrupts ovulation and eventually leads to infertility. “Our findings suggest that the focus should shift from treating insulin resistance in peripheral tissue to taming insulin sensitivity in the pituitary and ovaries,” says lead investigator Sheng Wu, Ph.D., of the Johns Hopkins Children’s Center. Obesity-induced infertility is being treated by lowering blood insulin to counter the effects of insulin resistance before. A 2010 study by the same team discovered that the pituitary gland, insensitive to insulin in lean mice, became sensitive to elevated levels of insulin seen in human and rodent obesity. The insulin receptors in the pituitary glands of obese mice were removed and the researchers were able to partially re-establish fertility.It partially proves that the abnormal level of insulin that signals the pituitary is a cause of infertility. “In the original study, disrupting insulin signaling in the pituitary restored 50 percent of fertility in obese mice, but the search was on for the accomplice,” says senior investigator Andrew Wolfe, Ph.D., an endocrinologist at the Johns Hopkins Children’s Center. “Our new findings point to the ovaries.” In the ovary, the testosterone production is being put into intense that disrupts the ovulation.

In the latest study, the methodology is briefly discussed: a lean mice and mice made obese on a three-month high-fat diet received injections of progressively higher doses of insulin to mimic the effects of high circulating insulin seen in obesity, diabetes and PCOS. In lean mice, the ovaries and pituitaries were insensitive to the hormone at low-dose injections, and responded only when injected with higher doses of insulin. The “trigger” doses corresponded to insulin levels typically seen in obesity. Obese mice with naturally elevated insulin levels exhibited high levels of insulin signaling in their pituitary and ovarian cells. When injected with insulin, the livers and muscles of obese mice showed greatly reduced response to insulin — or insulin resistance. Their ovaries and pituitary glands, however, responded to insulin injections, confirming that in obese mice, these reproductive organs escape the insulin resistance seen in other organs. The researchers focused on two signaling proteins, IRS-1 and IRS-2, regulators of cell-insulin communication involved in the development of insulin resistance in liver and muscle tissue to determine the insulin sensitivity. The scientists hypothesized that in the pituitary and ovaries, these messenger proteins would remain dormant under normal insulin levels, but would get activated once exposed to high levels of insulin. Indeed, the researchers found, the pituitary glands of obese mice showed higher IRS-2 signaling activity compared with lean mice, while the ovaries of obese mice had higher signaling activity in both IRS-1 and IRS-2 proteins, compared with lean mice.

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  1. [...] the Johns Hopkins scientists say the real culprit appears to be insulin … Read more on Heal Blog (blog)Related posts:Obstetrics, Gynecology and Infertility: Handbook for Clinicians; Pocket EditionThe [...]

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