World Diabetes Day is being marked on November 14 – this year also marks the centenary since scientists Sir Frederick Banting (a Canadian surgeon) and John Macleod (a Scottish professor of physiology and biochemistry) were jointly awarded the 1923 Nobel Prize in Physiology or Medicine “for the discovery of insulin”. A truly landmark accomplishment – just the year before, they had managed to successfully treat, for the first time, a 14-year-old boy with diabetes using insulin extracted from dogs. Thus, the treatment of diabetes mellitus was born.
Since this initial discovery of insulin, treatment of diabetes has come a long way. Today, there are many different formulations of insulin to choose from, allowing a more individualised approach. This apart from several medications available to treat patients with type 2 (non-insulin dependent) diabetes mellitus, that variously help stimulate the production and release of insulin from the pancreas, sensitise the body to insulin or increase the excretion of glucose in urine.
Nevertheless, current medications are all ineffective at actually slowing down progression of the disease. So, how could we achieve that?
We know that toxic clumps (or aggregates) of a protein called the islet amyloid polypeptide (IAPP) accumulate and destroy the insulin-producing β-cells in the pancreas. This process critically contributes to the development of diabetes. However, we still do not understand sufficiently well how the IAPP aggregates form, and why they are so damaging to the β-cells. Furthermore, can we stop the aggregates from forming in the first place, or at least can we neutralise their toxicity?
We know that toxic clumps (or aggregates) of a protein called the islet amyloid polypeptide (IAPP) accumulate and destroy the insulin-producing β-cells in the pancreas
These are questions we are currently trying to address and find answers to, in our research at the Dept. of Physiology and Biochemistry and Centre for Molecular Medicine of the University of Malta. We have been investigating how the IAPP aggregates harm intracellular organelles called mitochondria, in which chemical reactions occur to generate cellular energy (ATP) that is used to release insulin into the bloodstream.
We are also collaborating closely with the Max Planck Institute for Multidisciplinary Sciences in Göttingen, Germany, on trying to identify small molecules that can throw the spanner in the works, so to speak, of IAPP aggregation. We already have exciting data showing that it is indeed possible to interfere with IAPP aggregation and toxicity using specifically-designed compounds.
Ultimately, we hope that our mechanistic-based approach will translate into new effective medication that is able to slow down, or even perhaps halt altogether, progression of the disease.
That is in the future. Meanwhile, however, we should never forget prevention – more physical activity and a healthy balanced diet come at the top of the list – to disrupt the 21st century epidemic that is diabetes.
Neville Vassallo is an associate professor at the Department of Physiology and Biochemistry, University of Malta. Project ‘MITOLIPID’ is funded by the Research Excellence Programme of the Malta Council for Science and Technology.
Sound Bites
• Up to one in 20 new diabetes cases could be linked to COVID infection, data suggests. Canadian scientists have examined records from almost 630,000 people and found that those testing 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 referred to as “type 3 diabetes”. Scientists have used cutting-edge microscopy techniques to obtain very high-resolution images of pathological clumps of IAPP protein, called fibrils. Amazingly, the structure of IAPP fibrils is very similar to that of fibrils in the brains of individuals with Alzheimer’s disease.
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DID YOU KNOW?
• The earliest historical notes on diabetes are those found in the ‘Ebers Papyrus’ from 1550 BC. They were authored by Hesy-Ra, one of the physicians in Ancient Egypt, who wrote about a disease with “too great emptying of the urine” – relating to the passage of large volumes of urine, a typical symptom of diabetes.
• The physician who added “mellitus” (Latin for sweet or honey) to the name of the disease was Thomas Willis (1621–1675), who took note of the sweet taste of urine from such patients.
• Recent estimates put the number of cases of diabetes worldwide at 537 million, of which 90 per cent are type 2 diabetics. Numbers are expected to double to 1.3 billion by 2050.
• Type 2 diabetes is not known to spontaneously occur in rodents, like mice and rats. This is because of subtle changes in the structure of the IAPP protein.
For more trivia see: www.um.edu.mt/think.