Supplementary Material for: Diabetic Phenotype in the Small Intestine of Zucker Diabetic Fatty Rats

Background/Aims: In contrast to streptozotocin
(STZ)-induced rodent models of diabetes, there are no thorough
characterizations of the intestinal phenotype and the underlying changes
in the global gene-expression of genetic models of diabetes, such as
the Zucker diabetic fatty (ZDF) rat. The aim of the present study was to
characterize the intestine in the ZDF rat. Methods: The
intestine of ZDF rats and lean controls was examined macroscopically and
histologically, and ribonucleic acid sequencing (RNAseq) was performed
in samples of jejunal mucosa. Results: We observed an
increased mass and length of the small and large intestines in ZDF rats.
RNAseq showed an increased expression of Pdk2 and Pdk4,
which are involved in the regulation of glucose and fatty acid
metabolism, and increased expression of genes involved in
gluconeogenesis and peroxisomal beta-oxidation in jejunal mucosa. Conclusion:
Intestinal enlargement in ZDF rats is likely driven by increased food
intake, since (i) it also occurs in obese and normoglycemic Zucker fatty
rats, and (ii) insulin treatment of STZ-induced diabetic rats reduced
the food intake and mass of the small intestine. Results from RNAseq
indicate that small intestinal epithelial cells in ZDF rats have
developed insulin resistance, and support that a normal physiological
effect of insulin in the enterocytes is the regulation of glucose
metabolism.