Researchers in the US have discovered surprising effects on hormone production that could accelerate diabetes.
Researchers in the US have made a breakthrough discovery in the development of diabetes – that could be caused by spikes in blood glucose levels.
The study, funded by our sister charity, Diabetes Research & Wellness Foundation in the US, highlighted what they termed a “glucose toxicity” effect that helps to drive the development of both type 1 and type 2 diabetes.
The results of the study were recently published in Molecular Medicine, providing new evidence about how beta cells behave at slightly raised levels of blood glucose.
In people with diabetes, tiny clusters of insulin-producing “beta cells” in the pancreas do not produce enough of the hormone to keep people healthy, and their blood glucose levels climb.
As a result, their beta cells then function very differently than the cells do in people without diabetes who have ‘normal’ blood glucose levels.
Researchers said their findings were “surprising” in that the changes in beta-cell behaviour begin to happen when the blood glucose levels were barely elevated and still within the pre-diabetes range.
Gordon Weir, MD, study lead and Senior Investigator and Senior Staff Physician who holds the DRWF Chair at Joslin Diabetes Center, Boston, Massachusetts, said: “These slightly high concentrations of glucose are enough to really confuse the cell.”
Dr Weir and colleagues found changes in gene expression that affect not just how well the cells function but their ability to divide and grow, as well as their vulnerability to autoimmunity and inflammation.
Dr Weir, who is also Professor of Medicine at Harvard Medical School, has previously studied a type 2 diabetes phenomenon called “first-phase insulin release” and how this release is shut down as the disease progresses, that has so-far eluded an explanation by fellow researchers.
Dr Weir explained, that in healthy people with normal blood glucose levels, the body responds quickly to glucose with a big spike of insulin secretion.
Dr Weir said: “If then you take people who have slightly higher glucose levels, above 100 mg/dl, which is still not even diabetes, this first-phase insulin release is impaired. And when the level gets above 115 mg/dl, it's gone. So virtually all the beta cells don't respond to that acute stimulus.”
Fortunately, researchers said the cells eventually do wake up and respond to other stimuli well enough to keep blood glucose in a pre-diabetes range.
Dr Weir suggested the latest findings may improve the understanding of the rapid death of beta cells that experienced by people before they are diagnosed with type 1 diabetes, in addition to explaining the so-called “honeymoon” period some people experience after diagnosis, in which their blood glucose levels are relatively easy to control.
If insulin treatments can bring the remaining beta cells back down to only slightly elevated glucose levels during this period, the cells could function much better.
Dr Weir added that glucose toxicity could also trigger the loss of first-phase insulin release as type 2 diabetes develops.
Dr Weir said: “Somehow these beta cells with no evidence of inflammation end up not secreting properly. We think these higher glucose levels are causing the trouble.”
Additional evidence for the role of higher blood glucose levels in type 2 diabetes follows the results of people whose blood glucose levels return to healthy levels, putting the condition into remission.
Dr Weir said: “Their first-phase insulin release also comes right back to normal, which fits perfectly with our hypothesis.”
Andrea Stancik, Executive Director of DRWF Inc. a 501c3 non-profit organisation, sister charity to DRWF and part of the Diabetes Research & Wellness Foundation international network, said: “The Diabetes Research & Wellness Foundation has been supporting Dr Gordon Weir throughout his career. We are proud of Dr Weir's and his colleague's breakthrough discovery of hormone production. It is critical that organisations like DRWF and private donors continue to support researchers like Dr Weir to provide research milestones like these.”
Aref Ebrahimi, a Harvard student working in the Weir lab, was lead author on the paper. Joslin’s Jennifer Hollister-Lock, Brooke Sullivan, Ryohei Tsuchida and Susan Bonner-Weir were co-authors. Lead support came from the National Institutes of Health, the Diabetes Research and Wellness Foundation and Joslin’s Diabetes Research Center.
Read the report in Molecular Medicine
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