Treatment with DPP-4I Anagliptin or α-GI Miglitol Reduces IGT Development and the Expression of CVD Risk Factors in OLETF Rats.

Abstract

It has been reported that postprandial hyperglycemia from the pre-diabetic stage, especially from the impaired glucose tolerance (IGT) stage, is positively associated with subsequent incidences of cardiovascular diseases (CVD) and type 2 diabetes. In this study, we aimed to investigate whether treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4I) or an α-glucosidase inhibitor (α-GI), either of which suppresses postprandial hyperglycemia, reduces the expression of CVD risk factors in an IGT animal model. A DPP-4I, anagliptin (1,200 ppm), or an α-GI, miglitol (600 ppm), in the diet was administered for 47 wk to Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model for spontaneously-developed type 2 diabetes, at the IGT stage. We examined whether each treatment reduced the expression of CVD risk factors such as inflammatory cytokines/cytokine-like factors in peripheral leukocytes and adhesion molecules in the aortic tissues and circulation. Treatment with either drug reduced IGT development and repressed expression of the interleukin-1β, tumor necrosis factor-α, S100a9, and S100a11 genes in peripheral leukocytes in the fasting state at weeks 25 and 39. The mRNA levels of E-selectin in aortic tissues and protein levels of the soluble forms of E-selectin and ICAM-1 in arterial blood were significantly lower in the anagliptin and miglitol groups than in the control group. Our results suggest that long-term treatment with anagliptin or miglitol in OLETF rats at the IGT stage suppresses the expression of inflammatory cytokines in peripheral leukocytes and adhesion molecules in aortic tissues.

• Authors: Chihiro Imai, Tomomi Harazaki, Seiya Inoue, Kazuki Mochizuki, Toshinao Goda
• Journal: Journal of nutritional science and vitaminology (J Nutr Sci Vitaminol (Tokyo)) Vol. 61 Issue 4 Pg. 313-21 ( 2015) ISSN: 1881-7742 [Electronic] Japan
• PMID: 26440638 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Cell Adhesion Molecules
• Cytokines
• Hypoglycemic Agents
• Interleukin-1beta
• Pyrimidines
• S100 Proteins
• Tumor Necrosis Factor-alpha
• miglitol
• 1-Deoxynojirimycin
• anagliptin

Topics

• 1-Deoxynojirimycin (administration & dosage, analogs & derivatives)
• Animals
• Aorta (metabolism)
• Blood Glucose (drug effects)
• Cardiovascular Diseases (etiology, prevention & control)
• Cell Adhesion Molecules (drug effects)
• Cytokines (drug effects)
• Fasting (metabolism)
• Hyperglycemia (complications, drug therapy)
• Hypoglycemic Agents (administration & dosage)
• Interleukin-1beta (metabolism)
• Leukocytes (metabolism)
• Male
• Postprandial Period (drug effects)
• Pyrimidines (administration & dosage)
• Rats
• Rats, Inbred OLETF
• Risk Factors
• S100 Proteins (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)