UVic researchers identify a pathway to better cognitive health for diabetics
November 04, 2024
Interleukin-10 is a naturally occurring protein in mammals and it’s generally considered to be anti-inflammatory, which is a good thing. However, a 番茄社区 research team has recently shown that sometimes it actually creates a problem instead.
Their study, recently published in the journal , reports that diabetic mice had persistently high levels of interleukin-10 (IL-10), and that this led to small blood vessels in the brain becoming clogged with red blood cells. The reduced blood flow in the brain, in turn, led to impaired cognitive function. Importantly, the team also showed that treating diabetic mice with IL-10 blockers helped prevent cognitive impairment.
“We started the study not knowing what signalling pathway to follow,” says Sorabh Sharma, the lead author of the article and a post-doctoral fellow in neuroscientist Craig Brown’s lab at the time. “We were looking for the exact mechanism for the cognitive impairment so we screened for 27 different cytokines [proteins] and IL-10 stood out at all stages of diabetes.”
This was a surprise to the team because “the literature said that IL-10 is anti-inflammatory,” Sharma explains.
“Our findings reinforce the notion that IL-10 signalling can play both protective and deleterious roles, depending on the specific cell, organ or disease,” Brown says.
“This study is novel. We didn’t expect it to go this way. We knew the mice had cognitive problems, so we assumed there would be blood flow problems. Then our colleagues tested the mice’s blood for signals of inflammation and they found consistently high levels of IL-10. These findings suggest a new, targetable signalling pathway that future therapeutics can exploit to prevent the negative impact of diabetes on brain health.”
A growing number of Canadians have some form of diabetes, at a cost to the Canadian healthcare system of $15.6 billion a year. Although diabetes-related disease in the heart, kidney and eye is well documented, the brain appears to be particularly sensitive — diabetics are at significantly greater risk for developing cognitive impairment and vascular pathology such as stroke.
But Brown and the team don’t only care about the dollars or outcomes in older people. They want to help address the problems that diabetes causes from the start, and help with longer-term social issues too.
“Human cultures are very centred around food,” Brown says, “and physical activity is very important for health generally. For people with Type I diabetes, who are dealing with limitations to food and activity in order to balance their glucose levels from a very young age, it can be very isolating.”
Sharma also has deeper reasons for seeking solutions to diabetics’ long-term health concerns: both of his parents have Type II diabetes. His PhD research focused on cognitive impairment in later life, so joining Brown’s lab to explore Type I diabetes was a natural extension.
Brown notes that a clinical trial by Australian researchers recently published in the New England Journal of Medicine found a connection between blocking a signalling pathway related to IL-10 and preserving the insulin-producing cells in the pancreas. While that study was different, the results correlate with the Brown lab’s.
“I’m encouraged that clinical trials are blocking a similar signalling pathway. It feels like we’re going in the right direction,” Brown says. “I hope future studies will explore this further.”
Sharma, currently seeing research impacts from the practitioner side, agrees.
“I’m curious to dig deeper,” he says, “to learn what we can do to make the research more clinically transformative.”
Rachel Goldsworthy
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