Glucose Levels Trigger Increase in Beta Cell Mass for Type 2’s

The authors suggest that novel strategies to increase beta-cell mass to treat type 2 diabetes might be developed if the mechanism can be determined. Many individuals with type 2 diabetes are diabetic because the cells of their body no longer respond to the hormone insulin, which is crucial for lowering blood sugar levels. However, before individuals become clinically diabetic their body tries to compensate for the increasing resistance to the effects of insulin by increasing both the amount of insulin secreted and the mass of insulin-secreting cells (beta cells) in the pancreas. Several factors have been shown to induce an increase in beta-cell mass, but exactly what triggers this in individuals consuming a high-fat diet has not been clearly established.

In a study, Takashi Kadowaki and colleagues from the University of Tokyo, Japan, show that in mice with high-fat diet-induced insulin resistance, changes in glucose concentration are likely to be the main trigger of increased beta-cell mass. The beta-cell mass of mice expressing only one copy of the gene encoding the sensor of blood glucose levels, GCK (Gck-/- mice), showed little increase compared with wild-type mice fed a high-fat diet, and the mice developed diabetes.

One important mediator of the beta-cell mass increase downstream of GCK sensing increased blood glucose levels, and was shown to be IRS2, as expression of IRS2 in Gck-/- mice partially prevented diabetes by increasing beta-cell mass. The authors therefore suggest that novel strategies to increase beta-cell mass to treat type 2 diabetes and overcome high-fat diet-induced insulin resistance might be developed if the mechanism linking GCK and IRS2 can be determined. However, in an accompanying commentary, Gordon Weir and Susan Bonner-Weir from the Joslin Diabetes Center remind us that before we develop new therapeutics "it is essential that glucose signals involved in beta-cell replication in both health and disease be carefully defined."

Glucokinase and IRS-2 are required for compensatory beta-cell hyperplasia in response to high-fat diet-induced insulin resistance. Journal of Clinical Investigation Jan 2006

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DID YOU KNOW:
Stroke Incidence Has Declined for 50 Years: The incidence of stroke has dropped over the last 50 years, but stroke still remains a major problem for older Americans, a new study shows. The findings, from the Framingham Heart Study, are based on an unusual half-century follow-up of more than 9,000 residents of the Massachusetts town who were first recruited in 1948. Since then, the risk of stroke by age 90 has decreased from 19.5 percent to 14.5 percent in men 65 and older, and from 18.0 percent to 16.1 percent for women. Journal of the American Medical Association, Dec. 27, 2006

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