A team of researchers from the University of Oxford has shed light on the mystery of how high blood sugar leads to type 2 diabetes.
Diabetes research is getting more and more advanced
The finding reveals that glucose metabolites can damage pancreatic beta cells, leading to the progression of type 2 diabetes, and disrupting this process could provide a new way to treat the disease.
The International Diabetes Federation estimates that more than half a billion people worldwide are currently living with diabetes, and the vast majority of them have type 2 diabetes, according to newatlas.com.
The disease is characterized by hyperglycemia, in which high levels of glucose circulate in the blood. Researchers have long known that type 2 diabetes is largely the result of poor diet and lack of exercise. High sugar consumption leads to type 2 diabetes by impairing the body’s ability to release insulin, the hormone known to lower blood glucose levels.
What the researchers clearly didn’t understand was how chronically high blood glucose levels damage our insulin-producing beta cells. Elizabeth Haythorne, a lead investigator on the new study, had previously established that chronic hyperglycemia can damage beta cells, so the next step was to determine exactly how this damage occurs.
“We realized that we needed to better understand how glucose impairs beta cell function so we could think about ways to stop it and thereby slow the seemingly inexorable decline in beta cell function in T2D.”, explains Haythorne.
In a series of animal studies and cell culture investigations, researchers have found that it is not glucose itself that affects the function of insulin-producing beta cells, but the products generated by the process of glucose metabolism. Researchers do not yet know exactly which specific glucose metabolites trigger this process, but they clearly show that inhibiting glucose metabolism can maintain insulin production, even in the presence of high blood glucose levels.
Interestingly, this finding is somewhat counterintuitive, with the researchers revealing that blocking glucose metabolism by inhibiting an enzyme called glucokinase actually improved insulin secretion in the animals. Frances Ashcroft, another researcher working on the study, said this finding is the opposite of what had previously been tested for the treatment of type 2 diabetes (T2D).
“Because glucose metabolism normally stimulates insulin secretion, it was previously hypothesized that increased glucose metabolism would increase insulin secretion in T2D, and glucokinase activators have been tested, with conflicting results”Ashcroft noted. “Our data suggest that glucokinase activators may have an adverse effect and, somewhat counterintuitively, that a glucokinase inhibitor may be a better strategy to treat T2D.”
Ashcroft points out that these findings are still very preliminary, so much work is needed before this type of treatment approach reaches clinical use. But this historic discovery is reshaping the way we think about developing new ways to treat type 2 diabetes.
“This suggests a potential way in which the decline of beta cell function in T2D could be slowed or prevented.” added Ashcroft.
The new study was published in Nature communications.
