A Novel Rat Model of Type 2 Diabetes: The Zucker Fatty Diabetes Mellitus ZFDM Rat

Abstract

The Zucker fatty (ZF) rat harboring a missense mutation (fatty, fa) in the leptin receptor gene (Lepr) develops obesity without diabetes; Zucker diabetic fatty (ZDF) rats derived from the ZF strain exhibit obesity with diabetes and are widely used for research on type 2 diabetes (T2D). Here we establish a novel diabetic strain derived from normoglycemic ZF rats. In our ZF rat colony, we incidentally found fa/fa homozygous male rats having reproductive ability, which is generally absent in these animals. During maintenance of this strain by mating fa/fa males and fa/+ heterozygous females, we further identified fa/fa male rats exhibiting diabetes. We then performed selective breeding using the fa/fa male rats that exhibited relatively high blood glucose levels at 10 weeks of age, resulting in establishment of a diabetic strain that we designated Hos:ZFDM-Leprfa (ZFDM). These fa/fa male rats developed diabetes as early as 10 weeks of age, reaching 100% incidence by 21 weeks of age, while none of the fa/+ male rats developed diabetes. The phenotypic characteristics of this diabetic strain are distinct from those of normoglycemic ZF rats. ZFDM rat strain having high reproductive efficiency should serve as a more useful animal model of T2D.

Involvement of spinal glutamate transporter-1 in the development of mechanical allodynia and hyperalgesia associated with type 2 diabetes

“…We found that ZDF rats developed mechanical hyperalgesia and allodynia over time, which were consistent with previous studies showing that ZDF rats develop peripheral neuropathy at a similar range of age 32,33. In addition, we found that ZDF rats exhibited enhanced basal extracellular levels of glutamate in the spinal cord, as compared with age-matched lean control rats.…”

Administrations of thalidomide into the rostral ventromedial medulla alleviates painful diabetic neuropathy in Zucker diabetic fatty rats

“…We found that ZDF rats became hyperglycemic at the age of 13 weeks. These results were consistent with some previous reports that have shown that ZDF rats develop diabetes at a similar range of age (Shiota and Printz 2012;Yokoi et al, 2013). Additionally, our study reported that ZDF rats exhibited increased levels of TNFα, IL-1β, and NFκB in the RVM at the age of 13 weeks, when ZDF rats were first confirmed as diabetic.…”

Antioxidant diet and sex interact to regulate NOS isoform expression and glomerular mesangium proliferation in Zucker diabetic rat kidney

“…It remained elevated at 20 weeks: 443 ± 29.3 mg/dL (n = 13) in females and 439 ± 48.8 mg/dL (n = 11) in males. In the non- diabetic Zucker rat, random blood glucose averages between 114-136 mg/dL over the same age range (Yokoi et al, 2013). …”