Effects of atorvastatin and insulin in vascular dysfunction associated with type 2 diabetes
C M Sena1, P Matafome, T Louro
1Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. csena@ci.uc.pt.
Abstract:
Atorvastatin and insulin have distinct mechanisms of action to improve endothelial function. Therefore, we hypothesized that atorvastatin and insulin therapies alone or in combination could have beneficial effects on endothelium-dependent vascular reactivity, oxidative stress, inflammation and metabolic parameters in Goto-Kakizaki (GK) rats, a model of type 2 diabetes fed with atherogenic diet (GKAD). In parallel with the development of diabetes and lipid profile, the generation of oxidative stress was determined by measurement of lipid peroxides and oxidized proteins and the presence of inflammation was evaluated by assessing C-reactive protein (CRP). Additionally, endothelial dependent and independent vascular sensitivity to acetylcholine and sodium nitroprusside were evaluated. GKAD showed increased carbonyl stress, inflammation, fasting glycemia, dyslipidemia and endothelial dysfunction when compared to control GK rats. Noteworthy, supplementation with insulin deteriorated endothelial dysfunction while atorvastatin induced an improvement. Atorvastatin and insulin therapies in combination improved metabolic parameters, CRP levels and insulin resistance indexes and ameliorated endothelial dysfunction in GKAD rats while they were unable to reduce urinary 8-isoprostranes and plasma carbonyl compounds. The therapeutic association of atorvastatin and insulin provided a better metabolic control with a reduction in endothelial dysfunction in GKAD rats by a mechanism that involves an improvement in systemic inflammation.
Insights
Combining atorvastatin and insulin improved metabolic control and endothelial dysfunction in diabetic rats. While insulin alone worsened endothelial function, atorvastatin showed benefits, with the combination therapy reducing inflammation.
Area of Science:
- Biochemistry
- Pharmacology
- Endocrinology
Background:
- Type 2 diabetes is characterized by endothelial dysfunction, oxidative stress, and inflammation.
- Goto-Kakizaki (GK) rats fed an atherogenic diet (GKAD) serve as a model for type 2 diabetes with dyslipidemia and endothelial dysfunction.
Purpose of the Study:
- To investigate the effects of atorvastatin and insulin, alone and in combination, on endothelial function, oxidative stress, inflammation, and metabolic parameters in GKAD rats.
- To evaluate the impact of these therapies on endothelium-dependent and independent vascular reactivity.
Main Methods:
- GKAD rats were treated with atorvastatin, insulin, or a combination.
- Assessed oxidative stress (lipid peroxides, oxidized proteins), inflammation (C-reactive protein - CRP), and vascular reactivity (acetylcholine, sodium nitroprusside).
- Measured fasting glycemia, lipid profiles, and insulin resistance indexes.
Main Results:
- GKAD rats exhibited increased carbonyl stress, inflammation, hyperglycemia, dyslipidemia, and endothelial dysfunction compared to controls.
- Insulin alone worsened endothelial dysfunction; atorvastatin improved it.
- Combination therapy improved metabolic parameters, CRP levels, and insulin resistance, ameliorating endothelial dysfunction without reducing specific oxidative stress markers.
Conclusions:
- Atorvastatin and insulin combination therapy offers metabolic benefits and reduces endothelial dysfunction in GKAD rats, primarily through improved systemic inflammation control.
- Individual therapies have differential effects, with atorvastatin being beneficial for endothelial function and insulin potentially detrimental in this model.
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