- A research team has shown that cutting the formation of hybrid insulin peptides delayed the onset of type 1 diabetes in a mouse model.
- These unusual peptides appear to trigger the autoimmune T cells that attack insulin-producing cells.
- The work is still at the animal stage, but it offers a plausible route towards slowing or preventing disease before it fully develops.
Researchers at CU Anschutz have added another piece to the type 1 diabetes puzzle by targeting molecules called hybrid insulin peptides, or HIPs. These peptides are thought to help trigger the immune attack that destroys insulin-producing beta cells.
Type 1 diabetes develops when the immune system wrongly identifies part of the pancreas as foreign and starts attacking it.
For years, researchers assumed normal insulin proteins were the main target.
But the field changed when Thomas Delong and colleagues showed that the immune system was reacting to hybrid insulin peptides instead.
These are unusual peptide fragments formed by linking part of an insulin sequence to part of another protein.
Because that combined sequence is not directly encoded in the genome, the immune system may see it as foreign.
The new study looked at whether stopping these HIPs from forming could delay disease.
The researchers focused on an enzyme called cathepsin D, which appears to be involved in generating the peptides.
By modifying one of the two insulin genes in non-obese diabetic mice so cathepsin D could no longer act in the usual way, they were able to reduce HIP levels in beta cells.
That had a clear effect.
The mice showed less immune reactivity against insulin and diabetes developed more slowly.
After one year, 43% of the modified mice were still diabetes-free, compared with only 10% of normal mice.
The team is now modifying both insulin genes and says preliminary data suggest this cuts HIP formation by 80% to 100%.
That is a serious result, even if it is still confined to a mouse model.
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- Type 1 diabetes genetic risk may also be active in brain cells
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It does not mean a cure is around the corner.
Mouse findings do not always translate cleanly to people, and type 1 diabetes in humans is more complicated than any lab model.
But the logic is strong.
If HIPs are helping to switch the autoimmune attack on, then reducing their formation could become a genuine prevention strategy.
At the very least, this work moves the field from simply describing the immune attack to interfering with one of the triggers behind it.
