Improving the outcome of islet cell transplantation by inhibiting the Y1 receptor

Transplantation of insulin-producing islet cells from donors has long been explored as a potential treatment option of patients with Type 1 Diabetes. A major limitation of this technique is the shortage of donor organs; each patient would typically need multiple transplants from multiple donors in order to completely ditch insulin shots. So, there’s a need to find solutions to make the transplantation more efficient.

A new study published in Nature Communications has now shown that it might be possible to transplant fewer islet cells by boosting the function of the transplanted islet cells.

The study, conducted by Professor Herbert Herzog, A/Prof Shane Grey, and their colleagues at the Garvan Institute in Australia, focussed on a protein present on beta cells called the “Y1 receptor”. Y1 receptors act like an off switch for insulin release: when they’re present at high levels, less insulin is released, and vice versa, when the Y1 receptor is blocked, more insulin is released.

The researchers compared blood sugar levels in diabetic mice transplanted with either 60 or 300 mouse islets. Blood sugar levels were normalised in mice transplanted with 300 islets, but not in those transplanted with only 60. However, if the transplanted cells were lacking Y1 receptors, then 60 islets were enough to normalise blood sugar.

Similarly, 60 islets were enough to normalise blood sugar levels if the diabetic mice receiving the transplant were then fed with “BIBO3304”, a compound that blocks the Y1 receptor. Even when the researchers stopped giving BIBO3304 to the mice after 10 days, the mice continued to have normal blood sugar concentrations until the end of the experiment 50 days later.

To see if the effects of BIBO3304 on the Y1 receptor is conserved in human islet cells, they next transplanted islet cells derived from human donors into the diabetic mice. Again, mice that were treated with BIBO3304 following the transplantation reached normal blood glucose levels, whereas the glucose concentrations in mice who received a placebo remained higher than normal.

Inhibiting the Y1 receptor following islet cell transplantation is yet to be tested in humans. If successful, this could make islet cell transplants more feasible in the future.

Link to study: https://www.nature.com/articles/s41467-017-00624-2

About Rina Soetanto

Rina Soetanto is currently doing her PhD in molecular biology. She also has an extensive background in pharmacology and pre-clinical cancer research, as well as an undergraduate science degree from the Australian National University with a double major in neuroscience and immunology.

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