Insulin Resistance Research

The presence of insulin resistance is strongly correlated with the development of metabolic syndrome. In fact, some investigators refer to metabolic syndrome as the insulin resistance syndrome.

Insulin is a hormone produced by the beta cells of the islets of Langerhans of the pancreas. Insulin is required for the uptake and utilization of the blood glucose by tissues of the body. In the absence of insulin the concentration of glucose in the blood becomes elevated, a condition known as diabetes mellitus. In addition, insulin has many other actions on the metabolism carbohydrates, lipids, and proteins.

In the absence of insulin, not only is the blood glucose level high, but intermediary metabolism is deranged. In the condition called insulin resistance, the action of insulin at the cellular level is impaired. Normal or even high levels of insulin may be present in the blood stream of persons with insulin resistance, but insulin fails to perform its functions normally at the cellular level.

The cellular action of insulin is initiated by its binding to the insulin receptor. This binding elicits a series of changes in signaling proteins within the cell that set off a cascade of metabolic actions. Insulin resistance can occur either because of a defect in insulin binding to its receptor or to "post-receptor" defects; with the latter, the spread of insulin-stimulated signals throughout the cell is deranged.

The major site of glucose utilization is muscle, although other tissues use glucose. Insulin facilitates tissue uptake of glucose in all organs except the brain, which can use glucose without insulin. From the viewpoint of glucose metabolism, however, skeletal muscle accounts for most of insulin resistance. Nonetheless, insulin resistance can extend to other tissues, notably the liver, causing a generalized derangement of metabolism.

The connection between insulin resistance and metabolic syndrome is not fully understood. Most patients with insulin resistance have metabolic syndrome, but it does not necessarily follow that all persons with insulin resistance have metabolic syndrome. Besides insulin resistance, other factors including genetic ones are needed to develop the risk factors of metabolic syndrome. Genetic factors may elicit the components of metabolic syndrome in the presence of insulin resistance: atherogenic dyslipidemia, hypertension, elevated plasma glucose, a prothrombotic state, and a proinflammatory state.

The Center for Human Nutrition has projects to understand the contribution of genetics to the metabolic syndrome. One project is the Lipodystrophy Project.