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DPP-4 (CD26) Inhibitor Alogliptin Inhibits Atherosclerosis in Diabetic Apolipoprotein E-Deficient Mice
- Publication Year :
- 2011
-
Abstract
- Dipeptidyl peptidase-4 (DPP-4 or CD26) inhibitors, a new class of antidiabetic compounds, are effective in the treatment of hyperglycemia. Because atherosclerosis-related cardiovascular diseases are the major complications of diabetes, it is important to determine the effect of DPP-4 inhibitors on atherosclerosis. In this study, nondiabetic and diabetic apolipoprotein E-deficient mice were treated with DPP-4 inhibitor alogliptin for 24 weeks, and atherosclerotic lesions in aortic origins were examined. Results showed that diabetes significantly increased atherosclerotic lesions, but alogliptin treatment reduced atherosclerotic lesions in diabetic mice. Metabolic studies showed that diabetes increased plasma glucose and that alogliptin treatment reduced glucose. Furthermore, immunohistochemistry study showed that diabetes increased interleukin-6 (IL-6) and IL-1β protein expression in atherosclerotic plaques, but alogliptin treatment attenuated diabetes-augmented IL-6 and IL-1β expression. In consistence with the observations from the mouse models, our in vitro studies showed that alogliptin-inhibited toll-like receptor 4 (TLR-4)-mediated upregulation of IL-6, IL-1β, and other proinflammatory cytokines by mononuclear cells. Taken together, our findings showed that alogliptin-inhibited atherosclerosis in diabetic apolipoprotein E-deficient mice and that the actions of alogliptin on both glucose and inflammation may contribute to the inhibition.
- Subjects :
- Apolipoprotein E
Blood Glucose
Male
medicine.medical_specialty
Apolipoprotein B
Dipeptidyl Peptidase 4
Interleukin-1beta
Inflammation
Enzyme-Linked Immunosorbent Assay
Biology
Real-Time Polymerase Chain Reaction
Article
Proinflammatory cytokine
Diabetes Mellitus, Experimental
chemistry.chemical_compound
Mice
Apolipoproteins E
Piperidines
Diabetes mellitus
Internal medicine
medicine
Animals
Humans
Uracil
Dipeptidyl peptidase-4
Triglycerides
Pharmacology
Mice, Knockout
Dipeptidyl-Peptidase IV Inhibitors
Cholesterol
Interleukin-6
U937 Cells
medicine.disease
Atherosclerosis
Endocrinology
chemistry
biology.protein
medicine.symptom
Cardiology and Cardiovascular Medicine
Alogliptin
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....b2074ced6367f6fc0f37972319a5dfae