Scientists have discovered protein markers unique to insulin-producing cells in the pancreas that could be used to develop treatment for people with type 1 or type 2 diabetes, according to two new studies.
In the first paper, researchers from Helmholtz Zentrum München: German Research Center For Environmental Health identified a marker gene expressed in a subset of pancreatic beta-cells (those cells that store and release insulin) that can be used to identify mature beta-cells for cell-replacement or regenerative therapies. The study was published in Nature.
“Islet cell heterogeneity is known for over 50 years, but the underlying mechanisms are not known,” lead author Prof Dr Heiko Lickert tells SBS. “The reason is a lack of marker genes.”
Diabetes affects around 1.7 million Australians, with type 2 diabetes accounting for around 85 to 90 per cent of all cases, and type 1 and gestational diabetes making up the rest.
Prof Dr Lickert’s team discovered that the gene Flattop (Fltp) was expressed in mature beta-cells in the Islets of Langerhans in the pancreas, but not in immature beta-cells. These ‘islets’ are essentially clusters of hormone-producing cells that make up around four to five per cent of a healthy adult pancreas.
This means that Fltp can be used by scientists to pinpoint specific clusters of beta-cells that can be targeted for regenerative therapy to replace lost cell mass and restore the pancreas’ ability to secrete insulin. Insulin production plays a crucial role in blood sugar regulation.
“Understanding islet and beta cell heterogeneity is the entry point to understanding cellular and functional plasticity of islet cells to trigger regeneration of functional islet cell mass in diabetic patients,” Prof Dr Lickert says.
“Triggering the receptors and pathways that associate with these populations might allow [us] to target beta cell proliferation and maturation for regeneration therapy.”
Human beta cells, which are critical for regulating blood sugar and preventing diabetes, actually come in different types.
In the second study, scientists from the Oregon Health and Science University studied pancreatic tissue samples from donors and identified the protein markers that four different subtypes of beta-cells in the pancreas. This study was published in Nature Communications.
“We found that human beta cells, which are critical for regulating blood sugar and preventing diabetes, actually come in different types,” lead researcher Dr Craig Dorrell tells SBS.
“The different types are very similar, but some of the rarer types in normal people are less good at secreting insulin.”
Dr Dorrell and his team analysed tissue samples from 17 healthy people and eight diabetic donors and found that not only did the subtypes differ in terms of gene expression and insulin secretion; they were also present in different numbers in diabetic patients.
“Perhaps the most important observation was that in type 2 diabetics, those ‘rare’ beta-cell subtypes are far more common, even becoming the majority in some cases,” he says.
“Clinically, there may be the possibility of trying to convert cells from one of the less functional subtypes into the most functional as a treatment for diabetes.”
He also says that the proteins identified in the study could be used as a diagnostic tool for early detection for people at high risk of developing type 2 diabetes, for example those who are obese or have a family history of the disease.
Prof Damien Keating, an expert in beta-cells and insulin secretion at Flinders University, says the “ground-breaking” studies reveal key biological mechanisms that were previously unknown.
“These are both excellent, ground-breaking studies that inform us about how complex our insulin secreting beta cells are,” Prof Keating tells SBS.
“These are both really important because our traditional view of beta cells has been that they are all basically the same as each other.”
He says the next step would be to develop drugs that can target the gene-protein pathways to ultimately increase the number and strength of beta-cell populations.
“If this can be done, the next step would be to transfer this knowledge into animal studies with a view to translating to the clinic and patients with diabetes.”
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