Poster Presentation Australian Islet Study Group 2013

Overexpression of oligosaccharide transferase 48 protects islet function in a low dose streptozotocin mouse model (#15)

Danielle Borg 1 , Felicia (Yih Teng) Yap 2 , Brooke Harcourt 1 , Melinda Coughlan 2 , Robyn Slattery 3 , Phillip Kantharidis 2 , Josephine Forbes 1
  1. Mater Research, Woolloongabba, QLD, Australia
  2. Division of Diabetes Complications, Baker IDI Heart and Diabetes Institute, Melbourne
  3. Department of Immunology, Monash University AMREP, Melbourne

Oligosaccharide transferase 48 (OST-48) is a subunit involved in the N-glycosylation of proteins facilitating proper folding and cellular localisation.  Malfunction of N-glycosylation can contribute to the accumulation of misfolded proteins as well as endoplasmic reticulum stress, each of which are implicated in pancreatic beta cell damage. Thus, we investigated the effect of human OST-48 overexpression on the development of type 1 diabetes. Male C57BL/6J (wild-type) or C57BL/6-Tg(UBC, DDOST)Jfo (OST-48) transgenic mice (n=6) were treated with either multiple low doses of streptozotocin (STZ; 40mg/kg) or vehicle control (citrate buffer) for 5 consecutive days and followed for 9 days post-injection. Prior to STZ treatment, overexpression of OST-48 led to higher fasting plasma insulin concentrations as compared to wild-type controls (p=0.04). Streptozotocin treatment elevated blood glucose levels (p=0.04) and significantly decreased the beta cell insulin content within islets of wild-type control mice (p<0.05). In contrast, streptozotocin treated mice with overexpression of OST-48 did not lower fasting plasma or islet insulin concentrations and islet secretory function was preserved. Improved glucose tolerance was also observed after 15 minutes (p=0.09) during IPGTT reaching significance by 30 minutes (p=0.01) in STZ-treated OST-48 transgenic mice compared to STZ-treated wild-type mice. These results demonstrate that the overexpression of OST-48 may protect pancreatic beta cell function from insult. Further insight into mechanisms responsible for this protection is required to understand the protective role for OST-48 within the pancreatic beta cells.