The CDK4-pRB-E2F1 pathway : A new modulator of insulin secretion.

Pancreatic β-cells are sensors of circulating glucose levels that control insulin secretion through a finely-tuned process. Under hyperglycemic conditions, glucose enters the cell, generates ATP, leading to a subsequent closure of voltage-dependent ATP channels, membrane depolarization, Ca²(+) entry and exocytosis of insulin vesicles. In pathological conditions, such as during type 2 diabetes (T2D), chronic hyperglycemia will ultimately result in decreased capability of β-cells to secrete sufficient amount of insulin to regulate glycemia. Therefore, understanding of the mechanisms of modulation of insulin secretion could be of interest for the treatment of diabetes. We have demonstrated that a particular cell cycle regulator, E2F1, is involved in pancreatic post-natal growth through its functions in the control of β-cell proliferation. Based on the observation that cell cycle regulators were highly expressed in non-proliferating β-cell, we hypothesized that these proteins could also have a direct role in pancreatic β-cell function. Altogether our data unravel a new function for these factors in the control of insulin secretion and open up new avenues for the treatment of diabetes.