Breakthrough Sheds Light on Cause of Diabetes

One of the root causes of type 1 diabetes may need rethinking – the condition may be triggered by faulty nerves in the pancreas, a new study reveals. Type 1 diabetes has long been described as an autoimmune disease in which the body’s immune system targets islet cells in the pancreas, eventually destroying their ability to produce insulin. However, what initiates the original attack on the pancreas had been unclear. It now seems that the nervous system may play a key role, according to researchers in Toronto, Canada. The team eliminated the disease in diabetes-prone mice by knocking out a set of faulty sensory nerves. They believe the finding could chart a new path in treatment of the disease in humans.

Michael Dosch at the Hospital for Sick Children in Toronto, and colleagues, had previously shown that not only islet cells, but the nerve tissue around them was affected as diabetes set in. For this reason, they suspected that certain sensory nerves of the pancreas might be involved. These nerves release a neuropeptide called "substance P" and are usually responsible for ensuring that islet cells produce the right amount of insulin.

The researchers used a chemical to obliterate these nerves in a breed of mice genetically predestined to develop diabetes. “It turns out if you remove these specific sensory nerves, the animals don’t get diabetes,” says Dosch. “It was stunning.”

When the researchers examined the nerves of diabetes-prone mice and compared them with normal mice, they found that the nerves of diabetes-prone mice do not producing enough substance P. This causes islet cells to overproduce insulin, leading to insulin-resistance and eventually islet-cell death. It is at this point, says Dosch, that the immune system is called into action, triggering diabetes.

The team wanted to know what would happen if they gave diabetic mice a top-up of substance P, so they injected some directly into the pancreas. Astonishingly, the diabetes disappeared overnight and the mice remained diabetes-free for weeks, and even months in some cases.

If the same were to happen in humans, a single injection could keep the disease at bay for years, says Dosch.

“These are interesting and original observations, and could potentially open new avenues for diabetes therapies,” says David Leslie of the Centre for Diabetes and Metabolic Medicine at Barts and The London, Queen Mary’s School of Medicine and Dentistry in London, UK.

The findings also support previous suggestions of a possible connection between autoimmunity and the nervous system. However, “there are almost certainly other mechanisms by which these mice, and indeed humans, get type 1 diabetes,” Leslie says.

About 85% of human diabetics are believed to have impaired sensory nerve function, but it has always been assumed to be a consequence of the disease, rather than a cause, says Dosch.

From January 2007, Dosch plans to look for evidence of sensory abnormalities in babies born to high-risk families, and will follow them to see if impairment is predictive of disease.

Journal Cell (vol 127, p 1123)

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FACT:
New Hormone Increases Beta Cells: Joslin Diabetes Center said a new study that it led may result in treatments that stimulate insulin production. The center said today that the new study shows that a neuropeptide, melanin-concentrating hormone, or MCH, plays a role in the growth of insulin-producing beta cells and the secretion of insulin; the hormone is found in the brain and is known for increasing people’s appetites. "When MCH induces appetite, it simultaneously increases insulin secretion from beta cells and enhances growth of beta cells," Joslin investigator Rohit Kulkarni said in a statement. "If the proteins that mediate the growth mechanism can be identified, it could lead to the development of new drugs that would enhance beta-cell growth to treat type 1 and type 2 diabetes."