RAGE deficient mice develop insulin secretory defects which are exacerbated with high fat feeding — ASN Events
  1. Schedule
  2. ADS Basic Orals - The stressed out islet, kidney and heart
  3. RAGE deficient mice develop insulin secretory defects which are exacerbated with high fat feeding

RAGE deficient mice develop insulin secretory defects which are exacerbated with high fat feeding (#78)

Felicia YT Yap 1 2 , Melinda T Coughlan 1 , Phillip Kantharidis 1 , Robyn M Slattery 3 , Brooke E Harcourt 4 , Vicki Thallas-Bonke 1 , Chen Chen 5 , Shane T Grey 6 , Josephine M Forbes 4
  1. Baker IDI Heart and Diabetes Institute, Melbourne, Vic, Australia
  2. Immunology Department, Monash University, Melbourne, VIctoria, Australia
  3. Immunology Department, Monash University, Melbourne, VIctoria, Australia
  4. Glycation and Diabetes Complications Laboratory, Mater Medical Research Institute, Brisbane, Queensland, Australia
  5. The University of Queensland, Brisbane, Queesland, Australia
  6. Garvan Institute of Medical Research, Sydney, New South Wales, Australia

Background/Aim: The receptor for AGEs (RAGE) is a pattern-recognition receptor, which has been suggested as a contributor to beta cell dysfunction. The aim of this study was to examine the effects of RAGE deficiency on beta cell function in vivo.

Methods: Wildtype (C57BL/6J; WT) and RAGE deficient (KO) mice were either fed normal or high fat chow for 16 weeks. Two groups of high fat fed WT mice  also underwent islet transplantation with either WT or RAGE KO islets after 12 weeks and followed for a further four weeks. Intraperitoneal glucose tolerance tests (IPGTT) were performed. Insulin secretory function was determined in isolated islets.

Results: High fat fed WT mice showed a lower RAGE expression in islets and impaired insulin secretion during IPGTT when compared to the wildtype mice fed normal chow. RAGE KO mice exhibited higher plasma glucose and insulin level concentrations during IPGTT on both chow or high fat diets as compared to WT mice. When insulin secretion assays were performed on islets isolated from these mice, RAGE KO islets had a higher basal insulin secretion but were not glucose responsive suggesting a specific islet defect with RAGE deficiency that was equivalent to WT islets treated with palmitic acid. In addition, RAGE KO islets transplanted into wildtype recipients which were high fat fed, performed worse than WT islets with respect to maintaining glucose homeostasis, consistent with an islet specific defect. 

Conclusions:  RAGE knockout mice have specific defects in insulin secretion which are exacerbated with high fat feeding.