The presence of insulin resistance is strongly correlated with the development of the metabolic syndrome. In fact, some investigators refer to the metabolic syndrome as the insulin resistance syndrome. A word is needed about what is meant by the term "insulin resistance". 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. Thus 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 the metabolic syndrome is not fully understood. Most patients with insulin resistance have the metabolic syndrome. However it does not necessarily follow that all persons with insulin resistance have the metabolic syndrome. Besides insulin resistance, other factors apparently are needed for the development of the risk factors of the metabolic syndrome. Among these genetic factors may predominate. In other words, genetic factors may elicit the components of the 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. Dr. Nicola Abate and Dr. Manisha Chandalia are working together on another project. It is aimed at understanding the causes of insulin resistance in populations that are unusually susceptible to this condition. One of these populations consists of urbanized South Asians. When South Asians move from the country into the cities, as increasingly occurs in India and other countries of South Asia , a great many rapidly develop insulin resistance and the metabolic syndrome. The same occurs when South Asians migrate to western countries ( United Kingdom and the United States ). Premature type 2 diabetes and coronary heart disease are especially common in these migrating South Asians. Apparently they have an underlying insulin resistance; and when they become sedentary and mildly overweight, the metabolic syndrome appears.
Drs Abate and Chandalia have a project to uncover the genetic basis of insulin resistance in South Asians and other populations that are predisposed to this condition. His research involves a combination of clinical genetics and molecular biology. Dr. Abate has received a research grant from the National Institutes of Health to support his research on the Insulin Resistance Project.
