Discovery Of Glucagon Secretion Mechanism

A University of Toronto research team has discovered a mechanism for secretion of the hormone glucagon, which could facilitate the development of new drug therapies for diabetic hyperglycemia.

Researchers – in collaboration with scientists in Sweden, the United Kingdom, Japan and the United States – describe how insulin can suppress alpha cell activity through activation of the GABA (gamma aminobutyric acid) receptor. Alpha cells release glucagon, which increases the level of glucose in the blood.

"We found out that insulin is able to modulate how much of the GABA receptor is expressed on the [alpha] cell surface," said Dr. Mohan Kumar, one of the lead authors of the paper and a senior research fellow in the division of endocrinology and metabolism at St. Michael’s Hospital in Toronto, a U of T-affiliated teaching hospital.

The implications of the research are most important for type 2 diabetes patients, who characteristically have hyperglycemia, or abnormally high blood glucose levels. Excessive glucagon secretion is a major cause of hyperglycemia in these diabetes patients.

"When you have chronic, long exposures of glucose and insulin, often seen in type 2 diabetes, the insulin signalling pathway in alpha cells appears to be disrupted," says the study’s senior researcher Qinghua Wang, an assistant professor of physiology and medicine at the University of Toronto who is based at St. Michael’s Hospital.

"If we understand this whole pathway better, we might be able to further learn what happens in the progression of type 2 diabetes. This in turn can lead to novel intervention strategies in treating hyperglycemia in diabetes."

January 10 issue of Cell Metabolism, the U of T

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