Development and characterization of a novel rat model of type 2 diabetes mellitus: The UC Davis type 2 diabetes mellitus UCD-T2DM rat

Bethany P. Cummings, Erin K. Digitale, Kimber Stanhope, James L. Graham, Denis G. Baskin, Benjamin J. Reed, Ian R. Sweet, Steven C. Griffen, Peter J Havel

Research output: Contribution to journalArticle

57 Citations (Scopus)

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 β-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 β-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 β-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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume295
Issue number6
DOIs
StatePublished - Dec 2008

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Type 2 Diabetes Mellitus
Insulin
Glucose
Age of Onset
Insulin Resistance
Fasting
Glycosuria
Animal Disease Models
Polyuria
Hyperphagia
Incidence
Hyperinsulinism
Glucose Tolerance Test
Leptin
Hyperglycemia
Sprague Dawley Rats
Pancreas
Obesity
Immunohistochemistry
Lipids

Keywords

  • β-cell
  • Diabetic rodent model
  • Hyperglycemia
  • Insulin

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Development and characterization of a novel rat model of type 2 diabetes mellitus : The UC Davis type 2 diabetes mellitus UCD-T2DM rat. / Cummings, Bethany P.; Digitale, Erin K.; Stanhope, Kimber; Graham, James L.; Baskin, Denis G.; Reed, Benjamin J.; Sweet, Ian R.; Griffen, Steven C.; Havel, Peter J.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 295, No. 6, 12.2008.

Research output: Contribution to journalArticle

Cummings, Bethany P. ; Digitale, Erin K. ; Stanhope, Kimber ; Graham, James L. ; Baskin, Denis G. ; Reed, Benjamin J. ; Sweet, Ian R. ; Griffen, Steven C. ; Havel, Peter J. / Development and characterization of a novel rat model of type 2 diabetes mellitus : The UC Davis type 2 diabetes mellitus UCD-T2DM rat. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2008 ; Vol. 295, No. 6.
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