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

• Published in: Journal of Nutritional Science and Vitaminology Vol. 61; no. 4; pp. 313 - 321
• Main Authors: IMAI, Chihiro, HARAZAKI, Tomomi, INOUE, Seiya, MOCHIZUKI, Kazuki, GODA, Toshinao
• Format: Journal Article
• Language: English
• Published: Japan Center for Academic Publications Japan 2015
• Subjects: 1-Deoxynojirimycin - administration & dosage; 1-Deoxynojirimycin - analogs & derivatives; adhesion molecules; Animals; Aorta - metabolism; Blood Glucose - drug effects; cardiovascular disease; Cardiovascular Diseases - etiology; Cardiovascular Diseases - prevention & control; Cell Adhesion Molecules - drug effects; Cytokines - drug effects; Fasting - metabolism; Hyperglycemia - complications; Hyperglycemia - drug therapy; Hypoglycemic Agents - administration & dosage; impaired glucose tolerance; inflammatory cytokines; Interleukin-1beta - metabolism; Leukocytes - metabolism; Male; postprandial hyperglycemia; Postprandial Period - drug effects; Pyrimidines - administration & dosage; Rats; Rats, Inbred OLETF; Risk Factors; S100 Proteins - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0301-4800; 1881-7742
• DOI: 10.3177/jnsv.61.313

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.