MEK/ERK Signaling in β-Cells Bifunctionally Regulates β-Cell Mass and Glucose-Stimulated Insulin Secretion Response to Maintain Glucose Homeostasis

In diabetic pathology, insufficiency in β-cell mass, unable to meet peripheral insulin demand, and functional defects of individual β-cells production are often concurrently observed, collectively causing hyperglycemia. Here we show that the phosphorylation ERK1/2 is significantly decreased islets db/db mice as well those a cohort subjects with type 2 diabetes. abrogation ERK signaling pancreatic through deletion Mek1 Mek2, glucose intolerance aggravates under high-fat diet–feeding conditions due insufficient lower proliferation reduced while dampening number exocytosis events molecules involved being less phosphorylated. These data reveal bifunctional roles for MEK/ERK homeostasis, i.e., regulating mass controlling β-cells, thus providing not only novel perspective understanding diabetes pathophysiology but also potential clue new drug development treatment.