Discovering how beta cell insulin production is regulated in humans
Dr Greg Kowalski aims to understand how beta cell insulin production is controlled in living humans.
Insulin is the most important metabolic hormone in the body, managing blood sugar levels and helping blood sugar enter the body’s cells so it can be used for energy.
It is produced and secreted from the pancreas by a highly specialised but relatively scarce number of endocrine cells known as beta cells. We know that inadequate secretion of insulin from pancreatic beta cells is the defining feature of both type 1 and 2 diabetes.
However, due to their location within the pancreas, as well as their relatively low numbers, it has not been possible to study the behaviour of beta cells in living humans. Accordingly, most beta cell research is either performed in animal models, or in cells from deceased donors in a laboratory dish.
Through a Diabetes Australia Research Program grant, Dr Greg Kowalski is developing a ‘liquid biopsy’ to understand how beta cell insulin production is controlled in living humans.
The liquid biopsy involves giving study participants a type of drink, known as ‘heavy’ water, that becomes incorporated into all newly made cellular proteins – including insulin, which is exclusively made in the beta cells and later secreted into the bloodstream.
In essence, the heavy water ‘tags’ new proteins, and the faster or slower the ‘tagging’ process occurs, provides a readout of how quickly proteins are made. By taking repeated blood samples from participants over a 1-2 week period, using advanced chemistry techniques, the research team can then look at the rate at which beta cell ‘tagged’ insulin is appearing in the bloodstream.
“The liquid biopsy will tell us about what happens to insulin within the beta cells that are tucked away deep in the pancreas,” Dr Kowalski explained.
“We will be able to get a readout of how long it takes pancreatic beta cells to manufacture insulin. Ultimately this could give us an idea of how fresh or how old the secreted insulin is, giving us new insight into pancreatic beta cell biology in living humans.”
Dr Kowalski said the technique could be used in future studies to examine beta cell biology in people with diabetes, potentially offering further understanding of the defects that underlie diabetes.