Oral Presentation ESA-SRB-AOTA 2019

Effects of diet on human islet function (#92)

Heather Burns 1 , Rebecca Stokes 1 , Jennifer Chen 1 , Jenny E Gunton 1 2 3 4
  1. Westmead Institute for Medical Research, Westmead, NSW, Australia
  2. Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
  3. St Vincent's Clinical School, University of New South Wales, Kensington, NSW, Australia
  4. Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW, Australia

INTRODUCTION:  While it is well known that obesity increases the risk of type 2 diabetes, the effect of specific diets on human islet function is difficult to determine. In this study, we wish to examine the effects of a high fat diet on human islet function after transplant.

METHODS: Human islets were transplanted into immunodeficient mice which had been made diabetic with alloxan prior to transplantation. Ten female Rag-1KO mice (on C57Bl/6 genetic background) were each transplanted with 2000IEQ human islets under the kidney capsule. Eight weeks after the transplant, mice with functioning grafts (n=8) were commenced on high-fat diet (HFD, 45% of calories from fat) or continued on normal chow diet (n=4 each). Glucose and insulin tolerance tests (GTT and ITT) were performed before and after diet and metabolic measurement of energy expenditure was performed using Promethion metabolic cages.

RESULTS: 80% of transplant recipients (8 of 10) were normoglycaemic after islet cell transplantation. Mice placed on a HFD gained significantly more weight over the following 8 weeks compared to their chow diet counterparts. HFD mice also had higher daily non-fasting BSL readings than mice on chow diet, with one HFD mouse exhibiting persistent hyperglycaemia (BSL>17mmol/L), however differences in daily random BGL were not significant for the most part. GTT results at 8 weeks post diet commencement showed a significantly greater deterioration in the HFD group compared to the chow group, with a tendency to higher fasting BGL, significantly higher BGL readings at 15 and 30 minutes, and a significant change in overall glucose tolerance (p=0.0022).

CONCLUSION: Prolonged exposure to HFD results in significant weight gain and impairment of islet function in human islets transplants into diabetic mice. The onset of dysglycaemia is slower than seen in C57Bl/6 mice.5cf9b7440fdf7-Presentation1.jpg