GENETIC NETWORKS AND APPLIED SYSTEMS BIOLOGY

Presented by C. Ronald Kahn, President and Director, Joslin Diabetes Center, Harvard University

Diabetes and the Insulin-Signaling Network

Understanding a biological system demands understanding the details of its components, and their interactions. As an example, Ronald Kahn described his research into the pathways that control insulin action.

Kahn began by noting that the current epidemic of diabetes and obesity is having a tremendously deleterious effect on human health in the United States. He added, however, that “diabetes and obesity are really a small part of a much larger problem that we call the metabolic syndrome.” The metabolic syndrome includes a constellation of diseases that are linked to insulin resistance and, in many cases, to the effects of overnutrition and underactivity. These diseases include glucose intolerance and type II diabetes; obesity; hypertension; lipid abnormalities; accelerated atherosclerosis; fatty liver; reproductive dysfunction, particularly polycystic ovarian disease in women; and even Alzheimer’s disease and neurodegenerative diseases, which are more common in individuals with insulin-resistant states (see Box 3-1).

BOX 3-1

Glucose Metabolism and Insulin Resistance

A stable level of glucose in the blood is necessary to provide energy to the brain, muscles, and organs; and excess energy is stored in fat tissue. When glucose levels in the blood decrease, pancreatic beta cells produce glucagon, which stimulates the liver to mobilize glycogen stores to release glucose into the bloodstream. When glucose levels rise, pancreatic alpha cells produce insulin, which inhibits glucose output from the liver and stimulates muscle and fat tissue to absorb glucose from the blood.


In insulin resistance the liver, muscle, and fat do not respond to the presence of insulin, which in turn leads to elevated blood glucose levels. This increases signaling to tissue receptors, which respond, although at a minimal level, allowing glucose levels to remain elevated. In type II diabetes, however, tissue receptors are desensitized to glucose stimuli and blood sugar levels rise, leading to symptoms of diabetes and, if left uncontrolled, to diabetic complications.



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