Somatostatin inhibition may prevent dangerous drops in blood sugar in type 1 diabetes

Inhibition of the hormone somatostatin could provide a new therapeutic strategy to prevent dangerous drops in blood sugar levels in type 1 diabetes. This was demonstrated by a study conducted by the University of Gothenburg and other institutions. The proposed strategy would have the potential to save lives.

In healthy individuals, a drop in blood sugar results in the release of glucagon, a hormone that helps the liver produce glucose, which normalizes blood sugar levels. Glucagon has the opposite effect on the body to insulin, which lowers blood sugar levels. Both hormones are produced in the pancreas.

People with type 1 diabetes lack insulin but also glucagon. When glucagon is not released during a drop in blood sugar, it leads to dangerously low blood sugar levels, a condition that causes about 10% of all diabetes-related deaths. type 1.

Restored ability to fend off drops in blood sugar

The current study, published in the journal Natural metabolismpresents a potential new therapeutic strategy against dangerous drops in blood sugar levels in type 1 diabetes. One of the lead researchers is Patrik Rorsman, professor of cellular endocrinology at the Sahlgrenska Academy at the University of Gothenburg and also active at the University of Oxford.

The researchers looked at groups of hormone-producing cells from the pancreases of humans and mice. They were able to show that in type 1 diabetes, these islets are unable to release glucagon when blood sugar is low. Indeed, the hormone somatostatin is released in greater quantities in type 1 diabetes and inhibits the release of glucagon.

Meanwhile, experiments showed that blocking somatostatin in mice with type 1 diabetes could restore the pancreas’ ability to release glucagon during hypoglycemia, preventing dangerously low blood sugar levels. The blockade was carried out pharmacologically.

Mapping of previously unknown signaling

Using genetically modified mice in which beta cells were activated by light, called optogenetics, the interaction between different cell types in the pancreatic islets was also mapped: alpha cells that release glucagon, beta cells that release insulin and delta cells which release somatostatin.

The findings provide an underlying explanation for how the reduced proportion of functional beta cells in type 1 diabetes may be linked to the increased risk of low blood sugar levels, which has not been clear until now.

Anna Benrick is an associate professor of physiology at the Sahlgrenska Academy at the University of Gothenburg and one of the co-authors.

“The new findings highlight an important and previously unknown role of electrical signaling that occurs via open cellular connections between beta cells and delta cells,” she says. “If electrical connections are lost, glucagon release is reduced and the risk of blood pressure drops increases.

“The fact that this can be restored pharmacologically by blocking somatostatin opens the possibility of preventing dangerous drops in blood sugar in type 1 diabetes.”