A new study has uncovered a connection between juvenile onset, or type 1, diabetes and type 2 diabetes, similar diseases with very different causes. Type 1 diabetes occurs in people who lack insulin because their immune systems have destroyed the insulin-producing beta cells in the pancreas, whereas type 2 diabetes occurs in people whose bodies are less responsive to insulin, leading the pancreas to produce less of it. Without the necessary insulin to control glucose levels in the blood, damage to organs such as the heart, kidneys, eyes and nerves can occur.

Previous research from Garth Cooper's group at University of Auckland, New Zealand, suggested that type 2 diabetes is caused by the formation of toxic clumps of a hormone called amylin in the pancreas. This hormone is produced by beta cells, just like insulin, and the two hormones typically work together to regulate the body's response to sugar. Some of the amylin that is produced can get deposited around pancreatic cells and tends to clump together; these clumps are toxic to beta cells and eventually destroy them. Cooper's team showed that the resulting decrease in the production of these hormones causes type 2 diabetes. Next, they wanted to determine whether toxic amylin deposits might be a causative mechanism in type 1 diabetes as well.

Modeling the activity of amylin in rodents is challenging because mouse amylin does not aggregate the way human amylin does. The researchers therefore created transgenic rodents that expressed human amylin for their studies. They compared mice with two copies of the human amylin gene (homozygous) and mice with one copy of the human amylin gene (hemizygous) in order to study the gene dosage effects. The homozygous mice developed clumps of human amylin in their pancreases and initially showed symptoms of prediabetes, including elevated insulin levels with transient insulin resistance, followed by a loss of beta cells similar to that seen in humans with type 1 diabetes. In contrast, the hemizygous mice had a prolonged prediabetes stage; extensive clumping of amylin and resulting dysfunction of beta cells did not occur until adulthood, similar to the symptoms and progression seen in humans with type 2 diabetes (FASEB J. 10.1096/fj.14-251744; published 19 August 2014).).

The research provides strong evidence that type 1 diabetes results from the same mechanism as type 2 diabetes but starts at an earlier age and progresses more rapidly. This appears to be directly related to the level of amylin expression, providing a new potential target for future studies.