Pancreatic Islet Function: from RNA sequencing to electrical stimulation of the endoplasmic reticulum
The molecular knowledge of the pancreatic islets is dense, complicated material. Methods like pancreas patch-sequencing (patch-seq) can aid in gaining a better understanding of the molecular mechanisms of islet function within autoimmune diseases, such as diabetes. At the organelle level, it is established that the endoplasmic reticulum (ER) plays a significant role in diabetes, due to its electrical properties and relationship to calcium levels. Electrical stimulation of the ER has shown promising results in finding the cause of diabetes. Other portions of the body are involved in electrical stimulation experiments, like the pancreatic nerve, to gain more information on the causes and even possible treatments for diabetes.
What is PNES?
• Pancreatic nerve electrical stimulation
• map the nerve projecting to the pancreas and pLNs in mice
• minimally invasive surgical procedure to implant micro-cuff electrodes onto the nerve
Results of PNES
Identified a sympathetic nerve that projects into pLNs but not pancreatic islets. Electrostimulation of this nerve inhibited T1D progression in both a spontaneous and an adoptive transfer models of T1D with minimal bystander effects.
• This shows promising results to prevent T1D progression
The endoplasmic reticulum membrane interacts with almost all subcellular compartments in the cell, from the plasma membrane to the nucleus. The ER is well researched, but knowledge about the ER electrical excitability is limited. To compensate, researchers shifted their focus on the relationship between ER excitability & function, calcium concentrations, and diabetes. It was found that an electrical dysfunction in the ER could play a critical role in development of type 2 diabetes.
Pathways researched in the ER:
• The inositol pathway
• Camp Pathway
• NAADP pathway
–definition: electrophysiological profiling and single-cell RNA sequencing in the same islet cell
–why use it: to gain more knowledge about the PNES and ER, patch-seq is being used to evaluate the cell regulators, like beta cell regulators, involved in diabetes
–results: robustly identified unsuspected genetic regulators of human b-cell physiology
Bottom line: the pancreatic islets contain genetic regulators of human beta physiology, but the function of these islets can be altered using PNES, like methods of electrical stimulation in beta cell ER.