title: Diabetic Phenotype in the Small Intestine of Zucker Diabetic Fatty Rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Metabolic Disease Research, Novo Nordisk A/S, Copenhagen, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Hvid
authors.forename: Stina Rikke
authors.initials: SR
authors.lastname: Jensen
authors.forename: Brent M
authors.initials: BM
authors.lastname: Witgen
authors.forename: Christian
authors.initials: C
authors.lastname: Fledelius
authors.forename: Jesper
authors.initials: J
authors.lastname: Damgaard
authors.forename: Charles
authors.initials: C
authors.lastname: Pyke
authors.forename: Thomas Bovbjerg
authors.initials: TB
authors.lastname: Rasmussen
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D007420:Intestine, Large / Q000473:pathology; D007421:Intestine, Small / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009765:Obesity / Q000378:metabolism*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D017423:Sequence Analysis, RNA; D013393:Sucrase / Q000378:metabolism*; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: C000631436:Pdk2 protein, rat; C000631440:Pdk4 protein, rat; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D017346:Protein Serine-Threonine Kinases; D013393:Sucrase; D005947:Glucose