Development and characterization of a novel rat model of type 2 diabetes mellitus: the UC Davis type 2 diabetes mellitus UCD-T2DM rat
Language: 
English
Short Title: 
Development and characterization of a novel rat model of type 2 diabetes mellitus
Abstract: 

The prevalence of type 2 diabetes (T2DM) is increasing, creating a need for T2DM animal models for the study of disease pathogenesis, prevention, and treatment. The purpose of this project was to develop a rat model of T2DM that more closely models the pathophysiology of T2DM in humans. The model was created by crossing obese Sprague-Dawley rats with insulin resistance resulting from polygenic adult-onset obesity with Zucker diabetic fatty-lean rats that have a defect in pancreatic beta-cell function but normal leptin signaling. We have characterized the model with respect to diabetes incidence; age of onset; longitudinal measurements of glucose, insulin, and lipids; and glucose tolerance. Longitudinal fasting glucose and insulin data demonstrated progressive hyperglycemia (with fasting and fed glucose concentrations >250 and >450 mg/dl, respectively) after onset along with hyperinsulinemia resulting from insulin resistance at onset followed by a progressive decline in circulating insulin concentrations, indicative of beta-cell decompensation. The incidence of diabetes in male and female rats was 92 and 43%, respectively, with an average age of onset of 6 mo in males and 9.5 mo in females. Results from intravenous glucose tolerance tests, pancreas immunohistochemistry, and islet insulin content further support a role for beta-cell dysfunction in the pathophysiology of T2DM in this model. Diabetic animals also exhibit glycosuria, polyuria, and hyperphagia. Thus diabetes in the UC Davis-T2DM rat is more similar to clinical T2DM in humans than in other existing rat models and provides a useful model for future studies of the pathophysiology, treatment, and prevention of T2DM.

Author(s): 
Cummings, Bethany P.
Digitale, Erin K.
Stanhope, Kimber L.
Graham, James L.
Baskin, Denis G.
Reed, Benjamin J.
Sweet, Ian R.
Griffen, Steven C.
Havel, Peter J.
Item Type: 
Journal Article
Publication Title: 
American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Journal Abbreviation: 
Am. J. Physiol. Regul. Integr. Comp. Physiol.
Publication Date: 
Dec 2008
Publication Year: 
2008
Pages: 
R1782-1793
Volume: 
295
Issue: 
6
ISSN: 
0363-6119
DOI: 
10.1152/ajpregu.90635.2008
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 18832086 PMCID: PMC2685302

Turabian/Chicago Citation

Bethany P. Cummings, Erin K. Digitale, Kimber L. Stanhope, James L. Graham, Denis G. Baskin, Benjamin J. Reed, Ian R. Sweet, Steven C. Griffen and Peter J. Havel. Dec 2008. "Development and characterization of a novel rat model of type 2 diabetes mellitus: the UC Davis type 2 diabetes mellitus UCD-T2DM rat." American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 295: 6: R1782-1793. 10.1152/ajpregu.90635.2008.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1152/ajpregu.90635.2008 | issn = 0363-6119 | volume = 295 | pages = R1782-1793 | last = Cummings | first = Bethany P. | coauthors = Digitale, Erin K., Stanhope, Kimber L., Graham, James L., Baskin, Denis G., Reed, Benjamin J., Sweet, Ian R., Griffen, Steven C., Havel, Peter J. | title = Development and characterization of a novel rat model of type 2 diabetes mellitus: the UC Davis type 2 diabetes mellitus UCD-T2DM rat | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | date = Dec 2008 | pmid = | pmc = }} </ref>