anagliptin and Hyperglycemia

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.

Topics: 1-Deoxynojirimycin; Animals; Aorta; Blood Glucose; Cardiovascular Diseases; Cell Adhesion Molecules; Cytokines; Fasting; Hyperglycemia; Hypoglycemic Agents; Interleukin-1beta; Leukocytes; Male; Postprandial Period; Pyrimidines; Rats; Rats, Inbred OLETF; Risk Factors; S100 Proteins; Tumor Necrosis Factor-alpha

Treatment with the dipeptidyl peptidase-4 inhibitor, anagliptin, or with the α-glucosidase inhibitor, miglitol, reduced the oral sucrose load-inducible expression of interleukin (IL)-1β, IL-18, tumor necrosis factor-α, S100a8, S100a9, S100a11, IL-1R2, IL-1Rn and tumor necrosis factor receptor 2 genes in peripheral leukocytes of Otsuka Long-Evans Tokushima fatty (OLETF) rats at the stage of impaired glucose tolerance. Inhibiting postprandial hyperglycemia reduced the expression of genes related to inflammation in peripheral leukocytes of OLETF rats.

Topics: 1-Deoxynojirimycin; alpha-Glucosidases; Animals; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Gene Expression; Hyperglycemia; Hypoglycemic Agents; Inflammation; Insulin; Interleukin-18; Interleukin-1beta; Leukocytes, Mononuclear; Male; Pyrimidines; Rats; Rats, Inbred OLETF; Receptors, Interleukin-1; S100 Proteins; Sucrose; TNF Receptor-Associated Factor 2