Kahn's research group excludes all of these as likely culprits in the new paper. When type 2 diabetes is diagnosed, the pancreas is usually producing increased insulin, but the body cannot respond to the insulin effectively, a condition called insulin resistance. Pancreatic beta cells respond by making extra insulin, but eventually the insulin is inadequate to overcome the insulin resistance. When glucose cannot get into the cells that need it, the sugar builds up in the blood. Normally, insulin triggers muscle and fat to send GLUT4 to cell membranes to transport glucose into the cells, where it is converted into complex carbohydrates and fat.
Sugars are cells' main source of fuel.
In nearly all species, including mice, rats, monkeys and humans, insulin acts as a dispatcher, calling the taxi cab GLUT4 out to the cell's membrane to transport glucose into the cell. Kahn's team targeted GLUT4 selectively in fat in mice to mimic how GLUT4 levels are decreased only in fat and not in muscle in human obesity and type 2 diabetes. Although the researchers knocked out insulin-mediated glucose uptake only in fat cells, they soon noticed liver and muscle cells' responses to insulin were markedly reduced. All of the mice showed insulin resistance similar to that found in human obesity. Insulin resistance is the first step toward diabetes.