Study: Patients with Type 2 Diabetes Produce Too Little Insulin, Too Much Glucagon

Patients with type 2 diabetes (T2D) do not secrete enough insulin and secrete too much glucagon, contributing to poor blood glucose because the glucagon-secreting α-cells have become resistant to insulin, according to a study by Uppsala University.

Insulin signals the body to absorb glucose in healthy individuals, reducing sugar in the blood and providing energy to tissues. In patients with T2D, this mechanism fails because the glucose-absorbing tissues become resistant to insulin and too little of the hormone is released into the blood, according to the study authors.

Additionally, those with T2D have elevated levels of glucagon, which 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 patients with T2D, too much glucagon contributes to a vicious cycle that exacerbates the high blood sugar levels of diabetics.

Although glucagon is vital to the body, little is known about how its release is regulated, according to the study authors. Researchers at Uppsala University used advanced microscopy techniques to further investigate how glucagon-producing α-cells are controlled by glucose.

The research 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 patients with T2D, the regulation was distributed, and high glucose no longer blocked the release of glucagon.

The research team isolated the α-cells and separated them from their tissue context in the pancreas, where the cells behaved in a “diabetic” manner and continued to secrete glucagon, even when glucose was elevated. According to Omar Hmeadi, one of the study leaders, the reason for this is because of α-cells blocked by insulin and other hormones that are released at high blood glucose from nearby cells.

When the cells are separated from each other, the cell-to-cell communication is lost and glucagon secretion proceeds even when it should not.

Further, α-cells in T2D become resistant to insulin, much like liver, fat, and muscle. This concludes that glucagon release is no longer inhibited during the mealtime rise in blood glucose, leading to elevated levels of the hormone in T2D, according to the study authors.

The researchers hope that their findings will lead to future studies for a better understanding of human T2D and guide the development of better treatment strategies.

REFERENCE

Type 2 diabetes: too much glucagon when α-cells become insulin resistant. Uppala Universitet. https://www.uu.se/en/news-media/press-releases/press-release/?id=5036&typ=pm&lang=en. Published April 20, 2020. Accessed April 22, 2020.