THE roots of type 1 diabetes might reach in an unexpected direction: faulty nerves in the pancreas could be to blame.
Type 1 diabetes has long been thought of as an autoimmune disease in which the immune system targets islet cells in the pancreas, eventually destroying their ability to produce insulin. Without insulin, the body can鈥檛 convert glucose into energy, so people with type 1 diabetes have to regularly inject themselves with insulin to survive.
What launches the original attack on the pancreas has been unclear, however. It now seems that the nervous system may play a key role, say researchers in Toronto, Canada, who eliminated the disease in mice by knocking out a set of faulty sensory nerves. They believe their findings could chart a new path in treating the disease in humans.
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Michael Dosch at the Hospital for Sick Children in Toronto and his colleagues had previously shown that the nerve tissue around islet cells is also affected as diabetes sets in. They suspected the involvement of certain sensory nerves of the pancreas that release a neurotransmitter called substance P; this, they discovered, has a role in ensuring that islet cells produce the right amount of insulin to deal with blood sugar.
The team used a chemical to obliterate the nerves in a strain of mice that had been bred to develop diabetes. 鈥淚f you remove these specific sensory nerves, the animals don鈥檛 get diabetes,鈥� says Dosch. 鈥淚t was stunning.鈥�
When the researchers examined the pancreatic nerves of diabetes-prone mice, they found that they don鈥檛 produce as much substance P as the nerves of normal mice. 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 wondered what would happen if the diabetic mice got a top-up of substance P, so they injected some directly into the pancreas. Astonishingly, the diabetes vanished overnight and the mice remained free of it for weeks and in some cases, months (Cell, vol 127, p 1123). If the same thing happens in humans, one injection could keep the disease at bay for years, says Dosch.
The findings support previous suggestions of a link between autoimmunity and the nervous system in diabetes, and could open up new avenues for therapies, says David Leslie of the Centre for Diabetes and Metabolic Medicine at Barts and The London, Queen Mary鈥檚 School of Medicine and Dentistry. However, he cautions, 鈥淭here are almost certainly other mechanisms by which these mice, and indeed humans, get type 1 diabetes.鈥�
About 85 per cent of human diabetics are believed to have impaired sensory nerve function throughout the body, but it has always been assumed to be a consequence of the disease, not a cause, says Dosch. From January, he plans to look for signs of such abnormalities in people with a family history of diabetes.
