title: 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.affiliation: Laboratory of Nutritional Physiology, Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Imai
authors.forename: Tomomi
authors.initials: T
authors.lastname: Harazaki
authors.forename: Seiya
authors.initials: S
authors.lastname: Inoue
authors.forename: Kazuki
authors.initials: K
authors.lastname: Mochizuki
authors.forename: Toshinao
authors.initials: T
authors.lastname: Goda
mesh_terms: D017485:1-Deoxynojirimycin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D015815:Cell Adhesion Molecules / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects; D005215:Fasting / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D053583:Interleukin-1beta / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D019518:Postprandial Period / Q000187:drug effects; D011743:Pyrimidines / Q000008:administration & dosage*; D051381:Rats; D020334:Rats, Inbred OLETF; D012307:Risk Factors; D009418:S100 Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D015815:Cell Adhesion Molecules; D016207:Cytokines; D007004:Hypoglycemic Agents; D053583:Interleukin-1beta; D011743:Pyrimidines; D009418:S100 Proteins; D014409:Tumor Necrosis Factor-alpha; C045621:miglitol; D017485:1-Deoxynojirimycin; C583175:anagliptin