Research on diabetic mice has revealed abnormal cells producing proinsulin and TNF-α in various organs. These abnormal cells are bone marrow-derived and found in Kupffer cells and stellate cells in the liver, ICC cells of Cajal in the intestines, microglia in the brain, osteoclasts in the bones, adipocytes, tissue macrophages, and vascular endothelial cells in the kidneys.

Investigations revealed that these abnormal cells originate from CD106-positive cells within short-term hematopoietic stem cells. The abnormality in these stem cells causes dysfunction in organs throughout the body, with cells that are supposed to regenerate damaged tissues losing their function due to diabetes.

We named this phenomenon “diabetes stem cells.” These cells remain in the body as the “indelible memory” of diabetes, exacerbating the disease. Abnormal stem cells increase with each high blood glucose episode, leading to vascular damage and organ dysfunction.

Our body has three homeostasis maintenance mechanisms: the nervous system, the immune system, and the endocrine system. We propose a fourth homeostasis system, the regeneration system, topped by long-term hematopoietic stem cells. Diabetes disrupts this regeneration system, making it an “incurable disease.”

In an experimentally created model of diabetic neuropathy, it was confirmed that removing the hyperglycemic trigger and eliminating the diabetes stem cells (pathological CD106-positive hematopoietic stem cells) can lead to healing. This means that diabetes persists as long as these diabetes stem cells exist.

Based on this knowledge, we are developing diagnostic drugs aimed at the early detection and removal of diabetes stem cells. The advent of these new diagnostic drugs could lead to fundamental treatments for diabetes, bringing hope to many patients.