Insulin resistance is a condition in which the insulin produced by the pancreas becomes less effective at lowering blood sugar levels. It is a defining feature of metabolic syndrome, along with obesity, hypertension and dyslipidemia -- high cholesterol and triglycerides. Insulin resistance is also a key factor in the development of type 2 diabetes and a risk factor for heart disease. The female hormone estrogen may play a role in protecting against insulin resistance and diabetes. Scientific studies are investigating the estrogen-mediated regulation of glucose levels.
Insulin Resistance Basics
Insulin is a hormone produced by beta-cells, a specialized kind of cell in the pancreas. Insulin released from the beta-cells helps other cells in the body take up and utilize blood glucose, which is produced by the breakdown of food by digestion. In insulin resistance, muscle, liver and fat cells fail to respond to the insulin secreted by the beta-cells. The body needs higher amounts of insulin in order to take up and use glucose. Persistent insulin resistance, marked by high levels of glucose and insulin in the blood, eventually leads to diabetes. Obesity, high blood pressure and abnormal cholesterol levels often coexist with insulin resistance to result in a condition called metabolic syndrome.
Risk factors for developing insulin resistance include obesity -- a body mass index above 25; excess weight, especially around the waist or an "apple shape; having a parent or sibling with diabetes; physical inactivity; and in women, having polycystic ovarian syndrome or PCOS.
Treatment and Prevention
Extensive lifestyle modification -- by increasing physical activity and maintaining a healthy weight -- is the first recommendation for patients with insulin resistance. Many drugs are used to treat insulin resistance and type 2 diabetes, if present, and other features of metabolic syndrome. However, according to the American Diabetes Association, Metformin is the only drug to be considered for preventing development of insulin resistance into diabetes.
Effects of Estrogen
Estrogen is a steroid hormone produced primarily in the ovaries, and to a much lesser extent in other cells, like fat tissue. Small amounts of estrogen are also produced in men. Estrogen production from the ovaries declines around and after menopause. The decrease in insulin sensitivity with menopause suggests that estrogen generally protects against insulin resistance in women. Moreover, loss of estrogen function, through changes in estrogen receptor, has been shown to cause insulin resistance and type 2 diabetes in a male patient.
Further evidence for the role of estrogen in glucose regulation comes from studies in lab-grown cells and animal models of human disease. Mice deficient in estrogen receptor -- a protein that binds estrogen within cells -- become obese and insulin resistant. Ablation of estrogen by removal of ovaries in animal models impairs insulin sensitivity. This effect, however, could be reversed upon supplementation with estrogen. Estrogen receptor also improves the survival and glucose-stimulated insulin synthesis of pancreatic beta-cells.
Mechanism of action
Estrogen acts directly on beta-cells to make them resistant to apoptosis -- a kind of cell death-- and increase insulin production. This mechanism is thought to assist the pancreatic cells to adapt to higher insulin demands associated with some conditions, like pregnancy and obesity. However inappropriate estrogen function, due to abnormal increases in estrogen or stimulation with estrogen-mimics like bisphenol-A, can actually provoke insulin resistance by exhausting beta-cells through overstimulation.
Estrogen has also been reported to have anti-inflammatory properties. For instance, a study published in 2002 in "Endocrine Reviews" found that a decrease in estrogen after menopause was associated with increased pro-inflammatory cytokines -- small proteins that amplify inflammatory response of the immune system. Increases in inflammatory molecules are associated with obesity-induced insulin resistance. These are some mechanisms by which estrogen provides protection against insulin resistance and additional studies are needed for a complete description of the role of estrogen in glucose regulation.
- National Diabetes Information Clearinghouse; Insulin Resistance and Pre-Diabetes
- "Gender Medicine"; Eliza B. Greer and Wei Shen; December 2008
- "Molecular and Cellular Endocrinology"; Angel Nadal, et al.; May 2009
- "Endocrine Reviews"; Changes in Proinflammatory Cytokine Activity after Menopause; Johannes Pfeilschifter, et al.; February 2002