Metabolic and genomic dissection of diabetes in the Cohen rat

Chana Yagil, Ronit Barkalifa, Marina Sapojnikov, Alexander Wechsler, David Ben-Dor, Sarah Weksler-Zangen, Nurit Kaiser, Itamar Raz, Yoram Yagil

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

We investigated the metabolic and genetic basis of diabetes in the Cohen Diabetic rat, a model of diet-induced diabetes, as a means to identify the molecular mechanisms involved. By altering individual components in the diabetogenic diet, we established that the dietary susceptibility that leads to the development of diabetes in this model is directly related to the high casein and low copper content in chow. The development of diabetes is accompanied by depletion of the acini from the exocrine pancreas and replacement with fat cells, while the appearance of the islets of Langerhans remains intact. With reversion back from diabetogenic to regular diet, the diabetic phenotype disappears but the histological changes in the exocrine pancreas prevail. Using positional cloning, we detected a major quantitative trait locus (QTL) on rat chromosome 4 with a chromosomal span of 4.9 cM, and two additional loci on chromosomes 7 and X. A screen for genes within that QTL in the rat and in the syntenic regions in mouse and man revealed only 23 candidate genes. Notable among these genes is Ica1, which has been causally associated with diabetes and bovine casein. We conclude that the development of diabetes in our model is dependent upon high casein and low copper in diet, that it is accompanied by histomorphological changes in the exocrine but not endocrine pancreas, that it is reversible, and that it is associated with a major QTL on chromosome 4 in which we detected Ica1, a high priority candidate gene.

Original languageEnglish
Pages (from-to)181-192
Number of pages12
JournalPhysiological Genomics
Volume29
Issue number2
DOIs
StatePublished - 24 Apr 2007

Keywords

  • Candidate genes
  • Diet-induced
  • Genetic susceptibility

ASJC Scopus subject areas

  • Physiology
  • Genetics

Fingerprint

Dive into the research topics of 'Metabolic and genomic dissection of diabetes in the Cohen rat'. Together they form a unique fingerprint.

Cite this