Type 2 diabetes is characterized by impaired insulin production and pancreatic beta-cell activity. MiRNAs are small, non-coding RNAs that inhibit gene expression necessary for cell growth and function. Researchers previously demonstrated that miR-125b-5p levels rise as a result of β cell-specific deletion of the crucial energy sensor AMP-activated protein kinase (AMPK). However, it was unknown how this miRNA acts in cells.
Investigators postulated that glucose controls the miR-125b-5p expression and that this miRNA mediates some of the harmful consequences of hyperglycemia in β cells. For a study, they demonstrated that glucose increases islet miR-125b-5p expression in an AMPK-dependent way and that short-term overexpression of miR-125b-5p reduces glucose-stimulated insulin secretion (GSIS) in insulinoma MIN6 cells and human islets.
An unbiased, high-throughput search in MIN6 cells revealed many miR-125b-5p targets, including the lysosomal hydrolase transporter M6pr and the mitochondrial fission regulator Mtfp1. MiR-125b-5p inactivation shortened mitochondria and increased GSIS in the human β-cell line EndoC-H1, but animals overexpressing miR-125b-5p exclusively in β cells (MIR125B-Tg) were hyperglycemic and glucose intolerant. (MIR125B-Tg) β cells displayed larger lysosomal structures and lowered insulin content and secretion.
They concluded that miR-125b is a glucose-regulated regulator of organelle dynamics that controls insulin secretion.