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 language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Regulatory Integrative and Comparative Physiology |
| Volume | 295 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 2008 |
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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 journal › Article
}
TY - JOUR
T1 - Development and characterization of a novel rat model of type 2 diabetes mellitus
T2 - The UC Davis type 2 diabetes mellitus UCD-T2DM rat
AU - Cummings, Bethany P.
AU - Digitale, Erin K.
AU - Stanhope, Kimber
AU - Graham, James L.
AU - Baskin, Denis G.
AU - Reed, Benjamin J.
AU - Sweet, Ian R.
AU - Griffen, Steven C.
AU - Havel, Peter J
PY - 2008/12
Y1 - 2008/12
N2 - 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.
AB - 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.
KW - β-cell
KW - Diabetic rodent model
KW - Hyperglycemia
KW - Insulin
UR - http://www.scopus.com/inward/record.url?scp=57749116205&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=57749116205&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.90635.2008
DO - 10.1152/ajpregu.90635.2008
M3 - Article
C2 - 18832086
AN - SCOPUS:57749116205
VL - 295
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 6
ER -