Mechano-stimulated insulin secretion in pancreatic beta-cell: signalling pathways and its applications in diabetes treatment

Diabetes mellitus (DMs) is a rapidly increasing chronic disease that threatens societal health and takes a significant part of public costs in Sweden and worldwide. DMs are characterized by inappropriate insulin secretion from pancreatic beta cells. The dysfunction of insulin secretion causes rising blood glucose and the development of DM.

Here we hypothesize that mechanical force via blood flow reaches islet cells and is sensed by the mechanosensory molecules that participate in regulating insulin secretion.The blood flux induces a 15 times higher flux speed in the islet than the surrounding exocrine tissues and is even more enhanced after diet by raising blood glucose.

Meanwhile, the raised blood glucose also increases beta-cell swelling and membrane intention.

These actions on the surface of islet cells produce a significant difference in mechanical force that can be sensed by beta-cell mechanosensors and further result in various activation of cell signalling, such as secretory pathways triggering insulin release.We therefore will focus on the following areas: (1) To explore the role of mechanical sensors in regulating insulin secretion. (2) To identify the physiologic stimuli that activate mechanotransduction in islet cells. (3) To establish a mechanical force producer and genetically encoded nanoparticles activation system to regulate insulin secretion. (4) To apply the developed system to diabetes as a new therapeutic strategy.