In healthy people, 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.
In a recent study from Uppsala University, researchers found that in people with type 2 diabetes, the glucagon-secreting α-cells have become resistant to insulin.
The study is published in Nature Communications. The lead author is Omar Hmeadi in Sebastian Barg’s research group at Uppsala University.
In the study, the team used advanced microscopy techniques to examine how glucagon-producing α-cells are controlled by glucose.
They showed that glucagon is secreted during periods of low glucose, while high levels of the sugar efficiently block its release.
However, in α-cells of type 2 diabetics, this regulation was disturbed and high glucose no longer blocked the release of glucagon.
To find out why the team isolated the α-cells and separated them from their tissue context in the pancreas.
Surprisingly, the cells now behaved in a ‘diabetic’ manner and continued to secrete glucagon even when glucose was elevated.
Why do isolated α-cells behave as if they were diabetic? It turns out that the α-cells in type 2 diabetes become resistant to insulin, much like liver, fat, and muscle.
This means that glucagon release is no longer inhibited during the mealtime rise in blood glucose, and this leads to elevated levels of the hormone in type 2 diabetes.
The researchers hope the findings will contribute to a better understanding of human type 2 diabetes and guide the development of better treatment strategies.
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