Effects of bezafibrate on insulin sensitivity and insulin secretion in non-obese Japanese type 2 diabetic patients.

The aim of the present study was to investigate the effect of bezafibrate on insulin sensitivity and insulin secretion in 30 non-obese Japanese type 2 diabetic patients with hypertriglyceridemia (serum triglycerides > 150 mg/dL). Insulin sensitivity was measured with homeostasis model assessment insulin resistance (HOMA-IR) proposed by Matthews et al. HOMA-B-cell function, proposed by Matthews et al validated against minimal model-derived insulin secretion, was used to assess pancreatic insulin function. Twenty-two patients were treated with glibenclimide and the rest were treated with diet alone. All patients were treated with bezafibrate (400 mg/d) for 3 months. There were no changes in diet and the dose of any medications used throughout the study. Fasting glucose, insulin, triglycerides, HDL cholesterol, and total cholesterol levels were measured before and after treatment of bezafibrate. After treatment of bezafibrate for 3 months, serum triglyceride levels significantly decreased from 277 +/- 30 to 139 +/- 9 mg/dL (P <.001) and serum HDL cholesterol levels increased significantly from 45 +/- 2 to 52 +/- 2 mg/dL (P =.003). Serum cholesterol level was unchanged during the study (198 +/- 7 v 201 +/- 7 mg/dL, P =.383). Fasting glucose (163 +/- 8 v 139 +/- 6 mg/dL, P =.006) significantly decreased after the treatment with bezafibrate. HbA1c levels decreased, although not statistically significant (7.50 +/- 0.25 v 7.17% +/- 0.19%, P =.147). On the other hand, fasting insulin (9.3 +/- 0.7 v 7.3 +/- 0.5 microU/mL, P =.010) and HOMA-IR (3.61 +/- 0.24 to 2.53 +/- 0.20, P <.001) levels decreased significantly after the treatment with bezafibrate. In contrast, HOMA-B-cell function did not change during the study (41.4 +/- 5.5 v 41.8 +/- 4.7, P =.478). There was no significant difference in body mass index (BMI) levels before and after the therapy (23.0 +/- 0.4 v 23.1 +/- 0.4 kg/m(2), P =.483). From these results, it can be concluded that bezafibrate reduces serum triglycerides, insulin resistance, and fasting blood glucose levels in non-obese Japanese type 2 diabetic patients.

Characterization of defectiveness in endogenous antigen presentation of novel murine cells established from methylcholanthrene-induced fibrosarcomas.

Three cell lines (4A1, 4C2 and 6D1 cells) derived from fibrosarcoma induced by the inoculation of 3-methylcholanthrene into C3H/HeN (H-2k) mice were examined for their ability to present antigens to CD8+ cytotoxic T lymphocytes (CTL). 6D1 and 4C2 cells were deficient in presenting endogenously synthesized influenza virus antigens to CTL, but they were able to present antigens when they were sensitized with a synthetic epitope peptide. The expression of the H-2 Kk gene in 4C2 and 6D1 cells was much reduced and was detectable only with Northern blot hybridization. The expression of two transporter genes (TAP1 and TAP2), examined by Northern hybridization, was also reduced in both cells, and negligible particularly in 4C2 cells. Interferon-gamma (IFN-gamma) treatment of these cells induced expression of Kk, TAP1 and TAP2 genes and rescued the defect of class I-restricted antigen presentation in 4C2 and 6D1 cells. Even after this treatment, however, antigen-presentation capability of 4C2 cells was still much lower than that of normal 4A1 cells. This finding suggests that 4C2 cells might have an additional defective gene(s), whose products are involved in the processing of class I-restricted antigen, besides the Kk and TAP genes, and this may explain the difficulty of 4C2 cells to induce tumour-specific immunity, as described previously. To our knowledge, the 4C2 cell is the first tumour cell postulated to have more than three defective genes involved in class I-restricted antigen presentation.