Too much glucagon when α-cells become insulin resistant tied to diabetes

Uppsala University researchers have found that type 2 diabetes devlops because the glucagon-secreting α-cells have become resistant to insulin. Patients with type 2 diabetes secrete not only too little insulin but also too much glucagon, which contributes to poor blood glucose control.

In healthy individuals, insulin signals the body to absorb glucose, thereby reducing the sugar in the blood and providing energy to tissues. In patients with type 2 diabetes this mechanism fails, because the glucose-absorbing tissues become resistant to insulin and because too little of the hormone is released into the blood. This leads to elevated blood glucose and long-term complications that often become disabling or even life-threatening.

Often, type 2 diabetics also have elevated levels of glucagon, another hormone that is released by the pancreas. Glucagon counteracts the effects of insulin by instructing the liver to release stored glucose into the blood. After a meal, the release of glucagon is normally blocked to prevent excessive production of glucose by the liver. When this fails in diabetic patients, too much glucagon contributes to a vicious cycle that exacerbates the already high blood sugar levels of diabetics. Despite this vital function of glucagon, relatively little is known about how its release is regulated. Using advanced microscopy techniques, a team led by Omar Hmeadi in Sebastian Barg's research group at Uppsala University now adds insight into how glucagon-producing α-cells are controlled by glucose.