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Sodium Channel Connects Epilepsy, Diabetes

A tiny pore or channel that governs the flow of sodium ions in and out of a brain cell where it can trigger nervous impulses and seizures also plays a pivotal role in the release of insulin and glucagon (hormones involved in maintaining levels of glucose in the blood) by islet cells in the pancreas, said researchers from Baylor College of Medicine.

“A more precise understanding of defective insulin signaling and the molecules that can amplify release may lead to important new strategies in both the molecular diagnosis and therapy of disorders such as diabetes and hypoglycemia,” said Dr. Jeffrey Noebels professor of neurology, neuroscience and molecular and human genetics at BCM, who is the senior author.

“None of the current medical textbooks show that sodium ion channels participate in physiological insulin or glucagon release,” said Noebels.

A mouse bred with a defective gene for this particular sodium ion channel had both seizures and a dramatically impaired ability to release insulin and glucagon from the beta islet cells, said Noebels. Studies of the mouse islet cells showed that the sodium ion channel plays an important role in the pathway that leads to release of the hormones insulin and glucagon.

For a long time, scientists knew that insulin release from the pancreas depends on the ability of the organ’s beta islet cells to sense the level of circulating glucose in the blood.

When sugar levels are high, the cell is depolarized by the closure of potassium channels, allowing a second key signal, calcium ions, to enter the cells. These trigger the release of small packets containing insulin to expel their contents in the bloodstream in a process known as exocytosis.

This is similar to the way neurons in the brain release neurotransmitters. However, in the brain, the process begins with the opening of a sodium ion channel. Until now, while researchers knew there were sodium ion channels in beta islet cells, they did not think that they took part in the process of releasing insulin or glucagon.

The mouse studies confirm that the sodium ion channel plays an important role, said Noebels.

“It seems curious, but the islet cells from this mouse are sending a clear message, ‘If you would like more sugar, please pass the salt,’ ” he said.

The full report can be found at http://endo.endojournals.org/cgi/content/full/150/3/1132.

Endocrinology.March, 2009

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