Scientists find that a hormone other than insulin plays important role in type 2 diabetes

by Barbara Hewitt on November 21, 2018

Insulin is only one half of the story about what goes wrong in the body with type 2 diabetes, say scientists who have discovered that another hormone called glucagon is also important.

The study of cells by scientist from the Oxford Centre for Diabetes, Endocrinology and Medicine, shows that glucagon, which has an opposite effect to insulin, is also disrupted in people with type 2 diabetes.


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The research, led by professor Patrik Rorsman from the Radcliffe Department of Medicine, found that exposure to high glucose levels for as little as 48 hours changes glucagon secretion from the pancreas, but there may be a way to reverse these effects to restore normalcy.

The scientists used mice that had been genetically altered to mimic the symptoms of type 2 diabetes, as well as islet cells from the pancreas donated by patients with type 2 diabetes, to find out more about how glucagon secretion is regulated

In particular they looked at the alpha cells in the pancreatic islets, excitable cells that can generate electrical pulses much like cells in the brain. Alpha cells and other pancreatic islet cells use these electrical signals to control the release of islet hormones which include both insulin and glucagon.

Study co-author Dr Quan Zhang, explained that the alpha cells release glucagon which helps the liver to convert its store of glycogen into glucose, which then gets released into the bloodstream. The result is more glucose in the blood.

Insulin, which is also released by the pancreas, has the opposite effect. It signals the body to absorb glucose from the bloodstream, resulting in less glucose in the blood.

Normally, high levels of glucose result in pancreatic beta cells releasing insulin, so that glucose levels go down, and low levels of glucose result in the pancreatic alpha cells releasing glucagon, so that glucose levels go up.

But this fine balance gets entirely disrupted in type 2 diabetes when high glucose levels instead spur pancreatic alpha cells to release even more glucagon, which just makes glucose levels spike even higher.

The team compared what happened in diabetic versus normal alpha cells, and found that exposure to high glucose levels for as little as 24 hours set off a complex cascade of cellular processes that led to more sodium being ‘pushed’ into the alpha cells.

This lowered the cells’ pH, which results in lower energy being available to the cell. The lower energy levels change the activity of an energy sensitive channel in the cell membrane, and ultimately result in the glucagon release going awry.

But crucially, the researchers were able to reverse too much glucagon secretion in both the cells and the mice by using a drug that stopped too much sodium from getting into alpha cells, thus blocking the chain of events that led to glucagon dysregulation right at the start.

However, high levels of glucose still left their mark. Overweight diabetic rats who had bariatric weight reduction surgery, similar to humans, or successful diabetes drug treatment still had protein changes in alpha cells caused by high levels of glucose even after their glucose levels returned to normal.

‘We’re still understanding the complex interplay that leads to diabetes, but we’re hoping that drugs that inhibit these protein changes might be one way of treating the disease,’ said Rorsman.


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