Charity funding has been awarded for a major new study which will aim to prevent glucose-induced damage to kidney function in people with diabetes.
Professor Paul Squires and Dr Claire Hills, from the School of Life Sciences at the University of Lincoln, UK, have been awarded a grant of more than £200,000 from Diabetes UK to examine how increased levels of glucose in people with diabetes can adversely affect kidney cell communications and contribute to the progression of kidney disease.
Their work will provide vital information about how kidney disease develops in people with diabetes, and ultimately help to alleviate and prevent the damage caused to normal kidney function by excess glucose.
"The UK prevalence of diabetes is predicted to increase from 2.9 million sufferers currently, to 5 million in 2025. Kidney complications now account for 21% of deaths in patients with type 1 diabetes and 11% of deaths in those with type 2," Professor Squires explained. "Diabetic nephropathy — a debilitating and potentially life threatening complication of diabetes — is the leading cause of end-stage kidney disease, and to identify future treatment options in our fight against this condition, we need to understand the basic mechanisms that prevent kidney cells from functioning correctly. That is exactly what our new research will aim to do."
In diabetes, sustained exposure to increased levels of glucose adds extra stress to normal kidney function. The resulting damage alters the basic characteristics of cells, making it impossible for them to fulfill their usual role. High levels of glucose cause the contacts between kidney cells to weaken, and as cells move apart they lose the ability to directly talk to each other. In the absence of advice from their immediate neighbours, cells begin to work independently and often respond inappropriately to normal signals.
This new research will examine how high levels of glucose affect the ability of the cells that line the small tubes of the kidney to communicate with each other and their surrounding environment.
Dr Hills said: "Through our previous research, we have already demonstrated that glucose reduces the stickiness between kidney cells. This loss of adherence impairs the way cells talk to one another and in turn, affects cell function. Importantly, we already have preliminary evidence which suggests that in patients with diabetic nephropathy, there is a change in expression of the proteins responsible for transferring information between kidney cells. In the absence of any information transfer, these cells are unable to respond effectively to changes in their immediate surroundings."
The group's research has found that as kidney cells begin to move apart, they rely less on direct cell-to-cell communication and switch to an alternative form of interaction that involves the release of local signals from pores in the cell's membrane.
These pores (made up of proteins called connexins) have been linked to the onset of several diabetes-related complications. They release signaling molecules to enable communication, but sustained communication in this way has been linked to kidney scarring and fibrosis (excess connective tissue build up during repair process). Scarring and fibrosis are linked to loss of kidney function, and are recognised as precursors to kidney failure and the need for transplantation.
Dr Hills explained: "In an attempt to maintain a meaningful conversation, the release of ATP from cells actually contributes to the on-set of kidney disease. Our new project will therefore see us collaborate with a number of clinical partners and an international biotech company who are able to supply new agents to block ATP release. We hope that this project will help us to provide valuable information about how to alleviate and prevent damage to normal kidney function, and the onset of kidney disease."
Anna Morris, Head of Research Funding at Diabetes UK, said: "We're very pleased to be funding Professor Squires' and Dr Hill's latest research into understanding the development of kidney disease in people with diabetes. We hope it will lead to the development of new treatments to combat the condition, and we're looking forward to following the team's progress.
"We're sincerely grateful to people that support Diabetes UK – we're only able to fund world-class research like this thanks to you."
The new research project, entitled 'Determining a role for connexin mediated cell communication in the progression of renal fibrosis in the diabetic kidney', will run for three years and is part of an extensive portfolio of diabetes research at the University of Lincoln.
This work is supported by Diabetes UK (grant number 16/0005427).