ARF influences diabetes through promoting the proliferation and malignant development of β cells

Diabetes is a common chronic disease. ARF is a new tumor suppressor, which is one hotspot of cell cycle regulators. The mutation of ARF is absent in nearly 50% of tumors. ARF plays an important role in many physiological processes, such as cell proliferation, cell senescence and cell cycle arrest. However, the molecular mechanism of ARF regulating is not clear at present. Our study aims to explore the mechanism of ARF in diabetes.

ARF-Tg mice and C57 mice were fasted for 12 hours before the experiment. STZ was injected at a dose of 45-65 mg/kg. The model was established for blood glucose ≥16.7 mmol/L, the level of sugar in urine was at 3 + -4+. The experiment was carried out when the mice was eight weeks. The levels of glucagon with or without doxycycline mice, the proliferation and apoptosis of β-cell after immunosuppressive therapy were determined by immunofluorescence assay. Immunofluorescence and immunohistochemistry were used to observe the changes of insulin and glucagon.

Forty-eight model mice (96%) were divided into two groups, each group has 24 mice, respectively. There was not significant difference of insulin and glucagon in both groups without induction. After induction, the level of insulin was increased in ARF-Tg mice, the neonatal β cells were not increased but the number of proliferation cells and apoptotic cells was increased. Sirolimus combined with tacrolimus can effectively inhibit the reversal of the development of diabetes, but the conclusions need to be further confirmed in clinical.

High expression of ARF can promote the occurrence of diabetes by accelerating cell proliferation and apoptosis. Immunosuppressive agents can effectively reverse this phenomenon.