The role of ERK1/2 signaling in diabetes: pathogenic and therapeutic implications

Abstract

ERK1/2 (extracellular signal-regulated kinase 1/2) is an important member of the MAPK (mitogen-activated protein kinase) family and is widely involved in many biological processes such as cell proliferation, differentiation, apoptosis and migration. After activation by phosphorylation, ERK1/2 can be transferred into the nucleus and directly or indirectly affect the activity of transcription factors, thereby regulating gene expression. More and more studies have shown that ERK1/2 plays an important role in diabetes and its complications, such as insulin secretion, islet β cell function, diabetic cardiomyopathy, diabetic nephropathy, renal fibrosis, lipogenesis, diabetic vasculopathy, etc. These effects reveal the complexity and diversity of the ERK1/2 signaling pathway in the pathogenesis of diabetes, and its activation and inhibition mechanisms in multiple physiological and pathological processes provide potential targets for diabetes treatment. The purpose of this mini-review is to explore the key role of ERK1/2 in diabetes and the progress of research on targeted inhibitors of ERK1/2, which provides new strategies for the treatment of diabetes.

Keywords: ERK1/2; MAPK; complications; diabetes; inhibitors.

FIGURE 1

The regulatory mechanism of ERK1/2 signaling in promoting insulin secretion and insulin resistance. High glucose can activate the ERK1/2 signaling pathway by increasing Ca²⁺ influx and ROS production, leading to the entry of activated ERK into the nucleus. ERK1/2 in the nucleus can then activate downstream promoters, promoting the proliferation of islet β cells and the secretion of insulin. Activated ERK1/2 can lead to increased serine phosphorylation and decreased tyrosine phosphorylation of RS1, thereby inhibiting the downstream PI3K/Akt signaling pathway of insulin and ultimately causing insulin metabolism disorders.

FIGURE 2

Simple diagram of the possible regulation of diabetic complications by ERK1/2. Stimulated by high glucose, activated ERK1/2 can cause diabetes complications in a variety of ways.