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J Diabetes Res. 2015;2015:261418. doi: 10.1155/2015/261418. Epub 2015 Apr 16.

Characterization of the Prediabetic State in a Novel Rat Model of Type 2 Diabetes, the ZFDM Rat.

Author information

1
Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
2
Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan ; Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
3
Hoshino Laboratory Animals, Inc., Ibaraki 306-0606, Japan.

Abstract

We recently established a novel animal model of obese type 2 diabetes (T2D), the Zucker fatty diabetes mellitus (ZFDM) rat strain harboring the fatty mutation (fa) in the leptin receptor gene. Here we performed a phenotypic characterization of the strain, focusing mainly on the prediabetic state. At 6-8 weeks of age, fa/fa male rats exhibited mild glucose intolerance and severe insulin resistance. Although basal insulin secretion was remarkably high in the isolated pancreatic islets, the responses to both glucose stimulation and the incretin GLP-1 were retained. At 10-12 weeks of age, fa/fa male rats exhibited marked glucose intolerance as well as severe insulin resistance similar to that at the earlier age. In the pancreatic islets, the insulin secretory response to glucose stimulation was maintained but the response to the incretin was diminished. In nondiabetic Zucker fatty (ZF) rats, the insulin secretory responses to both glucose stimulation and the incretin in the pancreatic islets were similar to those of ZFDM rats. As islet architecture was destroyed with age in ZFDM rats, a combination of severe insulin resistance, diminished insulin secretory response to incretin, and intrinsic fragility of the islets may cause the development of T2D in this strain.

PMID:
25961052
PMCID:
PMC4415487
DOI:
10.1155/2015/261418
[Indexed for MEDLINE]
Free PMC Article

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