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Any diabetes story

December 30th 2014

Any diabetes story, which attracts the attention of both the BBC News website and the Daily Mail is worthy of investigation. This was how the report of Pagliuca, Millman and Gurtler (all co-first authors) was feted in October, following publication in the journal ‘Cell’.

The authors describe a ‘scalable differentiation protocol’ that generates hundreds of millions of b-cells from human pluripotent stem cells. The b-cells expressed markers found in mature human b-cells, packaged insulin into secretory granules, and secreted quantities of insulin comparable to adult b-cells in response to a glucose challenge. In addition, they were able to secrete human insulin in a glucose-regulated manner after transplantation into mice. Finally, transplantation of the beta cells into diabetic mice led to resolution of their hyperglycemia.

This is clearly a potential step-change in the therapy of diabetes. The nearest current equivalent is islet cell transplantation, which is available in a small number of centres in the UK. There are various limitations to this therapy, which is only considered for patients with type 1 (insulin-dependent) diabetes (T1DM). First, it relies upon the availability of cadaver organs for viable human islets and the safety of modern cars means that suitable donors are less available. Second, the limited number of islets are gradually eroded by a rekindled autoimmune response, meaning that independence from insulin is a rare two years after transplantation. This has led to the procedure being indicated for patients with hypoglycaemia unawareness (symptoms typically return, even if patients continue to need insulin), rather than as a cure for T1DM. Finally, immunosuppressant regimes are required to protect the islets and these come with their own adverse effects.

Press reports following the Cell publication highlighted that senior investigator, Douglas Melton, has two children with T1DM. With this incentive, perhaps he can now lead the challenge to shield the b-cells from autoimmune attack…

Professor Steve Bain

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