World Diabetes Day is being celebrated on 14 November – this year marks the centenary of scientists Sir Frederick Banting (a Canadian surgeon) and John Macleod (a Scottish professor of physiology and biochemistry) being jointly awarded the 1923 Nobel Prize in Physiology or Medicine. Has also been celebrated. For the discovery of insulin.” Truly a historic achievement – exactly a year earlier, they had managed to successfully treat a 14-year-old boy suffering from diabetes for the first time using insulin extracted from dogs. Thus, the treatment of diabetes mellitus was born.
Since this initial discovery of insulin, much progress has been made in the treatment of diabetes. Today, there are many different formulations of insulin available to choose from, allowing for a more personalized approach. It is an addition to the many medications available to treat patients with type 2 (non-insulin dependent) diabetes mellitus that help stimulate the production and release of insulin from the pancreas in a variety of ways, desensitizing the body to insulin. Or increases the excretion of glucose in the urine.
However, current medications are ineffective in actually slowing the progression of the disease. So, how can we achieve this?
We know that toxic clumps (or aggregates) of a protein called islet amyloid polypeptide (IAPP) accumulate and destroy insulin-producing β-cells in the pancreas. This process seriously contributes to the development of diabetes. However, we still do not adequately understand how IAPP aggregates form, and why they are so harmful to β-cells. Furthermore, can we prevent aggregates from forming in the first place, or at least can we neutralize their toxicity?
We know that toxic clumps (or aggregates) of a protein called islet amyloid polypeptide (IAPP) accumulate and destroy insulin-producing β-cells in the pancreas.
These are the questions that we are currently trying to address and find answers in our research at the Department of Physiology and Biochemistry and the Center for Molecular Medicine at the University of Malta. We are investigating how IAPP aggregates damage intracellular organelles called mitochondria, which contain chemical reactions to generate cellular energy (ATP) that is used to release insulin into the bloodstream.
We are working closely with the Max Planck Institute for Multidisciplinary Sciences in Göttingen, Germany, in an attempt to identify small molecules that can interfere with the function of IAPP aggregation. We already have exciting data demonstrating that it is indeed possible to interfere with IAPP aggregation and toxicity using specifically designed compounds.
Ultimately, we hope that our mechanism-based approach will translate into new effective drugs capable of slowing, or perhaps completely stopping, disease progression.
That’s in the future. In the meantime, however, we must never forget prevention – more physical activity and a balanced healthy diet come at the top of the list to disrupt the 21st century epidemic that is diabetes.
Neville Vassallo is Associate Professor in the Department of Physiology and Biochemistry, University of Malta. Project ‘Mitolipid’ is funded by the Research Excellence Program of the Malta Council for Science and Technology.
• Data suggests that one in 20 new cases of diabetes may be linked to COVID infection. Canadian scientists examined the records of nearly 630,000 people and found that those who tested positive for COVID on PCR were significantly more likely to be diagnosed with type 1 or type 2 diabetes in the following weeks and months.
• Alzheimer’s disease is sometimes called “type 3 diabetes.” Scientists have used state-of-the-art microscopy techniques to obtain very high-resolution images of pathological clumps of IAPP proteins called fibrils. Surprisingly, the structure of IAPP fibrils is similar to fibrils in the brain of individuals with Alzheimer’s disease.
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Do you know?
• The oldest historical notes on diabetes are found in the ‘Ebers Papyrus’ dating back to 1550 BC. They were written by Hesi-Ra, one of the ancient Egyptian physicians, who wrote about a disease called “excessive voiding of urine” – which is related to the passing of large amounts of urine, which is a symptom of diabetes. There is a specific symptom.
• The doctor who added “Mellitus” (Latin for sweet or honey) The disease was named by Thomas Willis (1621–1675), who noted the sweet taste of the urine of such patients.
• According to recent estimates, the number of diabetes cases worldwide is 537 million, of which 90 percent are type 2 diabetics. The number is expected to double to 1.3 billion by 2050.
• It is not known whether type 2 diabetes occurs spontaneously in rodents such as rats and mice. This is due to subtle changes in the structure of the IAPP protein.
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