Health & Wellbeing

Oxford scientists discover key cause of type 2 diabetes

Oxford scientists discover key cause of type 2 diabetes
A study has found it isn't glucose damaging the body's ability to produce insulin but products of glucose metabolism that lead to type 2 diabetes
A study has found it isn't glucose damaging the body's ability to produce insulin but products of glucose metabolism that lead to type 2 diabetes
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A study has found it isn't glucose damaging the body's ability to produce insulin but products of glucose metabolism that lead to type 2 diabetes
A study has found it isn't glucose damaging the body's ability to produce insulin but products of glucose metabolism that lead to type 2 diabetes

A team of researchers from the University of Oxford has shed light on the mystery of exactly how high blood glucose leads to type 2 diabetes. The discovery reveals glucose metabolites can damage pancreatic beta cells leading to the progression of type 2 diabetes, and disrupting this process could offer a new way to treat the disease.

The International Diabetes Federation estimates over half a billion people around the world are currently living with diabetes, and the vast majority of them suffer from type 2 diabetes. The disease is characterized by hyperglycemia, where high levels of glucose circulate in the bloodstream.

Researchers have long known that type 2 diabetes is largely a result of poor diet and a lack of exercise. Chronically high sugar consumption leads to type 2 diabetes by damaging the body's ability to release insulin, the hormone known to lower blood glucose levels.

What researchers haven't clearly understood was exactly how chronic high blood glucose levels damage our insulin-producing beta cells. Elizabeth Haythorne, one of the lead researchers on the new study, had previously established that chronic hyperglycemia can damage beta cells so the next step was to work out exactly how this damage was occurring.

"We realized that we next needed to understand how glucose damages beta-cell function, so we can think about how we might stop it and so slow the seemingly inexorable decline in beta-cell function in T2D," explained Haythorne.

Across a series of animal studies and cultured cell investigations the researchers discovered it isn't glucose itself that is impairing the function of insulin-producing beta cells, but products generated through the process of metabolizing glucose. The researchers are still unclear exactly what specific glucose metabolites trigger this process but they do clearly demonstrate that inhibiting the metabolism of glucose can maintain insulin production, even in the presence of high blood glucose levels.

Interestingly, this finding is somewhat counter-intuitive, with the researchers revealing blocking the process of glucose metabolism, by inhibiting an enzyme called glucokinase, actually improved insulin secretion in animals. Frances Ashcroft, another researcher working on the study, said this finding is the opposite of what had previously been trialed to treat type 2 diabetes (T2D).

"Because glucose metabolism normally stimulates insulin secretion, it was previously hypothesized that increasing glucose metabolism would enhance insulin secretion in T2D and glucokinase activators were trialed, with varying results," noted Ashcroft. "Our data suggests that glucokinase activators could have an adverse effect and, somewhat counter-intuitively, that a glucokinase inhibitor might be a better strategy to treat T2D."

Ashcroft does stress these findings are still very preliminary, so plenty more work is needed before this kind of therapeutic approach reaches clinical use. But this landmark finding does reframe how we think about developing new ways to treat type 2 diabetes.

"This suggests a potential way in which the decline in beta-cell function in T2D might be slowed or prevented," added Ashcroft.

The new study was published in Nature Communications.

Source: University of Oxford

Stuart Lew
Would not inhibiting glucose metabolsim, also cause the T2 Diabetic to feel more tired? Which, in turn, would result in less excercise? We need something that dials in more energy, not less.
Whilst this research is clearly good news for type 2 diabetes sufferers, why on earth our respective governments are not doing a great deal more to combat the utterly cynical attitude of the food industry in promoting (arguably fraudulently) supposedly healthy foods which are rammed with heavily processed carbohydrate - mostly sugar. For my money, I would impose an immediate TV advertising ban on any processed food with a carb content greater than 30% in much the same way as we have already (in some countries at least) banned advertising for cigarettes and alcohol.
David Levine
The idea that type 2 diabetes is predominantly linked to high sugar diets is a misnomer. I won’t get into all the specific instances that catalyze the issue. I do however want to note that even if glucokinase is limited, yes energy production will decrease, but the body will switch to alternative pathway. Glycolysis is the predominant pathway for energy production but there is an alternative enzyme used for glucose metabolism. Glucokinase is primarily found in the liver while Hexokinase is found everywhere else. The idea I believe is that limiting glucokinase in the liver will increase insulin production to a level that combats deficiency. The Hexokinase would still exist so metabolism wouldn’t slow per-say. This leads to the dietary aspect that would need to be coupled with treatment for maximum effectiveness.
@ David Levine: David I have no idea what your background is and I have no desire to offend you but your comment does rather remind me of the decades worth of expert opinion the tobacco industry trotted out to defend cigarette smoking. In reality anyone with half a brain can see that eating too much sugar will stress the insulin-making aspect to our metabolism and overtime that stress will cause the system to fail; one well-acknowledged cause of type 2 diabetes. I totally accept this is not the whole picture but equally I do *not* accept that it is a complete coincidence that the food industry have been almost literally ramming this muck down our throats for the last 30 years and in the same time period the Western obesity crisis has reached epidemic proportions.

All this is of course an entirely separate issue to the issue of tooth decay, particularly amongst children, most at risk from highly targeted TV advertising for sweets and another extremely highly-sugared foodstuffs. Or is all that a misnomer, too?
The ancients practiced fasting, witholding food anywhere from 24 hours to a week or more. Some present day physicians have discovered that fasting is the most effective way to permanently reverse Type ll diabetes without prescription drugs.
Nice article Rich. But explanations of mechanisms that damage the beta cells and insulin production/release is not immediately useful. Inhibiting the glucokinase results in lower energy production - that is true. Not knowing what "glucose metabolism products" are doing the actual harm of beta cells is the problem with this research. No answers, just more questions.

Still, the incremental march of science is frustrating yet without the steady progress, the big picture cannot be realized. I look forward to a full understanding of the development of type II diabetes so we can EFFECTIVELY treat the disease caused by poor dietary choices and our western food supply.
Christian Lassen
Let's fix a bad diet with costly medications! And since that's not good enough, we'll add more costly medications to help the first ones!

Focus first on the diet. Doesn't matter how many ambulances you put at the bottom of the canyon to rescue the cars that go off the edge, the better thing to do would be keep the cars from going off the edge. There's HALF a BILLION people with Type II Diabetes and we just want to tell them all to become even MORE dependent on expensive medicine, when the solution is FREE. Even the cost of educating all these people would be a fraction of the cost and much less resource dependent.
@Christian Lassen - There isn't any money in addressing root cause.