Effect of Type 2 Diabetes in the Aortic Function of Female UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) Rats

Authors

Farjana Akther, University of the PacificFollow
Md Rahatullah Razan, University of the PacificFollow
Tia Tang, University of the PacificFollow
James L. Graham, University of California, DavisFollow
Kimber L. Stanhope, University of California, DavisFollow
Peter J. Havel, University of California, DavisFollow
Roshanak Rahimian, University of the PacificFollow

Poster Number

6a

Lead Author Affiliation

Physiology and Pharmacology

Lead Author Status

Doctoral Student

Second Author Affiliation

Physilogy and Pharmacology

Second Author Status

Doctoral Student

Introduction/Abstract

UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) rat is a novel validated model of type 2 diabetes mellitus. UCD-T2DM is characterized by polygenic, adult-onset obesity and spontaneous β-cell failure and, as a result, more closely models the pathophysiology of type 2 diabetes in humans than other rodent models.

Purpose

The objectives of this study were to determine the effect of diabetes in aortic function of female UCD- T2DM rats and to investigate the possible underlying mechanism of vascular function in this model.

Method

Endothelium-dependent vasodilation (EDV) to acetylcholine (ACh, 10^-8 to 10^-5M) was measured in intact aortic rings pre-contracted with phenylephrine (PE, 2µM). Endothelium-independent vasodilation to sodium nitroprusside (SNP, 10^-9 to 10^-5 M) was assessed in endothelium-denuded rings pre-contracted with PE (2µM). Furthermore, constrictor response curves to PE (10^-8 to 10^-5 M) were generated before and after incubation with L-NAME (200μM), an endothelial nitric oxide synthase (eNOS) inhibitor. Expression of molecules associated with insulin signaling and vascular response were also evaluated in aortic tissues.

Results

Endothelium-dependent vasodilation (EDV) to acetylcholine (ACh, 10^-8 to 10^-5M) was measured in intact aortic rings pre-contracted with phenylephrine (PE, 2µM). Endothelium-independent vasodilation to sodium nitroprusside (SNP, 10^-9 to 10^-5 M) was assessed in endothelium-denuded rings pre-contracted with PE (2µM). Furthermore, constrictor response curves to PE (10^-8 to 10^-5 M) were generated before and after incubation with L-NAME (200μM), an endothelial nitric oxide synthase (eNOS) inhibitor. Expression of molecules associated with insulin signaling and vascular response were also evaluated in aortic tissues.

Significance

These data, for the first time, show that the vascular function is altered in aortic rings of female UCD-T2DM rats. Impaired insulin signaling and decreased sensitivity of vascular smooth muscle to NO along with the enhanced contractile responsiveness to PE may in part contribute to the attenuated relaxation response to ACh in diabetic female rats. (Supported by NIHLBI, R15HL128988).

Location

DeRosa University Center

Format

Poster Presentation

Poster Session

Morning 10am-12pm