While it is clear that beta cells are being lost at the earliest stages of T1D, the events that are occurring in the beta cell during the initiation of T1D are not well understood. This report demonstrates that a particular type of cellular stress is occurring in beta cells prior to the onset of diabetes in mice. This stress, if unresolved, leads to defects in insulin production and secretion and ultimately beta cell death. This raises the intriguing possibility that defects in the beta cell might be a trigger that initiates T1D or accelerates disease progression and that therapeutic strategies that alleviate beta cell stress could be useful in preventing or slowing progression of T1D. Although this work deals only with animal models of T1D, the data are consistent with clinical observations that suggest that beta cells are not functioning properly before clinical onset of T1D.
Tersey, SA, Nishiki, Y., Templin, AT, Cabrera, SM, Stull ND, Colvin SC, Evans-Molina C, Rickus JL, Maier B, Mirmira RG. (2012) Islet Beta Cell Endoplasmic Reticulum Stress precedes the onset of Type 1 Diabetes in the Non-Obese Diabetic Mouse Model. Diabetes. Apr;61(4):818-27.
Ramifications for Individuals with Type 1 Diabetes:
This work suggests that therapeutic strategies that work to alleviate a particular type of cellular stress in the beta cell could be effective at preventing T1D onset or slowing progress of the disease, preserving beta cell mass and improving glycemic control. More work is required to identify suitable drug targets in the beta cell stress pathway and develop therapeutics to manipulate the pathway.
This study was funded in part by JDRF.