ATP6V1H deficiency impairs glucose tolerance by augmenting endoplasmic reticulum stress in high fat diet fed mice

Vacuolar H+-ATPase (V-ATPase) is a ubiquitous proton pump that mediates the proton transmembrane trans-portation in various cells. Previously, H subunit of V-ATPase (ATP6V1H) was found to be related with insulin secretion and diabetes. However, the mechanism by which ATP6V1H regulates insulin secretion and glucose metabolism remains unclear. Herein, we established a high-fat-diet (HFD) fed model with Atp6v1h(+/-;)mice and detected the expression and secretion of insulin and some biochemical indices of glucose metabolism, in order to explore the related mechanisms in beta-cells. Transcriptome sequencing, qPCR and western blot analysis showed that ATP6V1H deficiency worsened fatty acid-induced glucose tolerance impairment by augmenting endo-plasmic reticulum stress in beta-cells, and alternative splicing of ATP6V1H might be involved in this process. These results indicated that ATP6V1H deficiency increased the susceptibility to T2DM.

Automated summary

This study found that ATP6V1H deficiency worsens fatty acid-induced glucose intolerance and increases endoplasmic reticulum stress in beta-cells. Alternative splicing of ATP6V1H might be involved in this process, increasing susceptibility to T2DM.