ZUCKER DIABETIC FATTY (ZDF) RAT MODEL

ZDF rats have been extensively used to study the pathogenesis of type 2 diabetes and is a popular model for evaluating drug candidates for glucose lowering, insulin sensitizers, insulin secretogogues and anti-obesity compounds in pharmaceutical industry. ZDF rat is a sub-strain of Zucker fatty rat and is selectively inbred for hyperglycemia. These rats are characterized by a mutation in leptin receptor which causes obesity by 4 weeks of age due to hyperphagia. They become hyperinsulinemic, hyperlipidemic and exhibit impaired glucose tolerance. The male rats develop insulin resistance and glucose intolerance between 3 and 8 weeks of age and become overtly hyperglycemic between 8 and 10 weeks of age. Pancreatic exhaustion has been observed similar to human type 2 diabetes which results in rapid decline in plasma insulin levels starting at 10 weeks of age and worsens as they age and convert to frank diabetes by 10-12 weeks of age. The data shown below are the effect of the test compound on the plasma levels of fasting plasma glucose, triglycerides, free fatty acids, cholesterol, and liver HMG CoA Reductase mRNA expression in ZDF rats.

Triangulum scientists have several years of experience using ZDF rat model, and our scientists work with you for a custom design and run studies to demonstrate proof-of-concept, mechanism of action and the therapeutic efficacy of your test compounds. We also conduct end-point analysis, histopathology, and will assist you with professional interpretation of the data. Please contact us with your specific needs.

Relevant publications by our scientists:
1. Watts LM, Manchem VP, Leedom TA, Rivard AL, McKay RA, Bao D, Neroladakis T, Monia BP, Bodenmiller DM, Cao JX, Zhang HY, Cox AL, Jacobs SJ, Michael MD, Sloop KW, Bhanot S. Diabetes. 2005, 54(6):1846-1853. PMID: 15919808