Diabetes a result of decline in compromised beta cells

by Barbara Hewitt on January 30, 2014

Two scientific studies from the University of California in the United States have shed new light on the nature of beta cells, the insulin producing cells in the pancreas that are compromised in diabetes.

The first suggests that some cases of diabetes may be caused when beta cells are deprived of oxygen, prompting them to revert to a less mature state that renders them incapable of producing insulin. The second study demonstrates that acinar cells, pancreatic cells that do not normally produce insulin, can be converted to functional beta cells, a potential new avenue for treating the disease.

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Whether oxygen starvation or metabolic changes within the beta cells are the key drivers during the development of diabetes in some patients remains to be discovered

In the first study, a gene known as VHL was selectively deleted from beta cells in mice. Insulin production in these beta cells was sharply reduced, and over time the mice developed the physiological equivalent of type 2 diabetes.

Despite the fact that much research on type 2 diabetes is focused on insulin resistance, the team behind this first new study suggests that a decline in the function of beta cells over time may be a factor in many cases.

‘Some humans with a high body mass index have well performing beta cells, and some lean people have poorly performing beta cells. This mouse is a model of lean humans who develop type 2 diabetes,’ said Matthias Hebrok, director of the UCSF Diabetes Centre.

The team found that even modest weight gains in individuals with subpar beta cells may increase demand on the cells for insulin to a point that they begin to exceed their capacity. Whether oxygen starvation or metabolic changes within the beta cells are the key drivers during the development of diabetes in some patients remains to be discovered.

‘The beta cell is a highly sophisticated cell that produces tremendous amounts of insulin in a tightly regulated way. Starving it of oxygen turns a Porsche into a VW Beetle, a high octane race car into a car that you now have to fuel with low octane. It can still get from A to B, but it can’t get there as well as it should,’ explained Hebrok.

He believes that many cases of diabetes are the result of steady, long term declines in the function of already compromised beta cells as they cope with an increasing demand for insulin. ‘What we are unravelling here is a different way of looking at how diabetes occurs. It’s not that you’re perfectly fine and then you’re pre-diabetic and then you’re diabetic and then your beta cells die. Instead it’s a slippery slope where the beta cell function erodes over time,’ he added.

In the second study, researchers were able to restore normal insulin and glucose levels in mice with no functional beta cells by transforming other pancreatic cells into beta like cells.

Mice were first injected with a beta cell specific toxin that caused them to display symptoms of diabetes. Five weeks later, the diabetic mice were implanted with miniature pumps that continuously administered two signalling molecules known as cytokines for seven days.

Treatment with the two cytokines, epidermal growth factor and ciliary neurotrophic factor, restored glucose and insulin to normal levels in the mice, and the mice maintained normal blood sugar control eight months later when the study concluded.

‘Type 1 diabetes patients would greatly benefit from pharmacological therapies that create new beta cells, provided that the current findings in mouse models could be translated into the identification of druggable targets in the human pancreas, and provided we could put a stop to the ongoing autoimmune destruction of the beta cells,’ said researcher Luc Baeyens.

‘In the short run, this model could serve as a platform to identify and study new compounds with therapeutic potential. In the long run, despite these encouraging results, we are still quite a long way from taking this research from the bench to the bedside,’ he added.


The opinions expressed in this article do not necessarily reflect the views of the DiabetesForum.com Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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