Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Genetic Deletion of the Endoplasmic Reticulum Gene Herpud1 Results in Impaired Insulin Secretion (#106)

Diane Vue 1 , Maria Stathopoulos 1 , Nicole Wong 1 , Sof Andrikopoulos 1
  1. University of Melbourne, Heidelberg, Vic, Australia
Prolonged physiological stress which causes over secretion of insulin can result in β-cell dysfunction and ultimately type 2 diabetes. We have previously shown that the gene, Herpud1 has a function in the islet β-cell and insulin secretion. Herpud1 encodes the ER-resident protein HERP which plays a protective role in ER-stress related pathways. To determine the function of Herpud1 in the islet β-cell we obtained a knock-out mouse model with global deletion of Herpud1. These mice were studied at 8 weeks of age to determine whether the deletion of Herpud1 affected body weight and basal glucose and insulin levels as well as insulin secretory responses in vivo (using the intravenous glucose tolerance test - IVGTT).  The data show that there was no difference in body weight (Negative littermates: 21.4 ± 0.9 grams, Knockout: 19.8 ± 0.3 grams, p=0.08, n=5-7) or basal insulin levels (Negative littermates: 0.6 ± 0.1 ng/ml, Knockout: 0.5 ±0.1 ng/ml, p=0.20, n=5-7) between the Herpud1 knockout mice and their negative littermates. Basal glucose concentrations were lower in the knockout compared with the negative littermates (10.4 ± 0.8 mmol/L vs 8.3 ± 0.6 mmol/L, p=0.04, n=5-6).  Following the IVGTT Herpud1-deficient mice had a decrease in glucose-mediated insulin secretion compared with their negative littermates (AUC - negative littermates: 54.3 ± 6.7 ng/ml x 30min, Knockout 42.6 ± 3.3 ng/ml x 30 min, p = 0.03, n=5-6).  We conclude that the preliminary data suggest that Herpud1 plays an important role in the islet β-cell since its genetic deletion caused reduced insulin secretion in response to glucose.  Further studies will be performed to determine the mechanism of this reduction in secretion and whether a high fat diet worsens the phenotype of the mice.