[Summary] Drug naive, newly diagnosed type 2 diabetic subjects were randomized to Saxagliptin/Metformin / Rosiglitazone(Triple Therapy, n=23) or insulin 70 30 mix group(Intensive Insulin Therapy) (n=21) for 24 weeks. How did the 2 therapies influence fasting blood glucose, fasting insulin, C-peptide, and glucagon levels and the change of body weight were compared. This study was aimed to explore the comparative glycemic efficacy and impact on α/ β-cell function of two different antidiabetic therapies, triple combination therapy using saxagliptin/metformin/ rosiglitazone and intensive insulin therapy, for newly diagnosed type 2 diabetes mellitus. The results indicated that fasting blood glucose, HbA1C , insulin resistance index 2(HOMA 2-IR), glucagon and body mass index level were significantly decreased, and insulin secretion index 2 ( HOMA 2-% β) was increased significantly( P <0. 05) in triple therapy group, and the decreasing extent of HOMA 2-IR, glucagon, and body mass index were significantly greater than that in the intensive insulin group(P<0. 05). Triple therapy group has a stronger effect of reducing insulin resistance, as well as on inhibiting glucagon and promoting weight loss.

[Summary] Thirty-two SD rats were randomly divided into noraml control group(NC, n = 10) and high fat diet group(HF, n=22). 10 weeks later, the HF group rats were injected STZ(30 mg/ kg) to set up the model of diabetes complicating with nonalcoholic fatty liver disease (NAFLD). Then, HF group were randomly divided into model control group(MC, n = 8) and Saxagliptin intervene group( M + S, n = 8). The M + S group were made an intervention with Saxagliptin(10 mg·kg-1 ·d-1 ) for 8 weeks. At the end of 18 weeks, the fasting blood glucose, serum insulin, liver function, liver weight, tumor necrosis factor alpha, and interleukin 6 were measured. HOMA-IR was calculated. Western bolt was used to determine the expression of NF-κB in hepatic tissue. The level of the indexes above increased in the MC group than in the NC group. But the indexes above mentioned in M + S group were ameliorated. The expression of NF-κB was significantly up regulated in MC group as compared with the NC group, and significantly reduced in the M+S group than in the MC group. The results of correlation analysis revealed that TNF-αand IL-6 were positive correlated with HOMR-IR, respectively. Saxagliptin can effectively reduce the blood glucose level and alleviate insulin resistance, then further relieve the inflammation of liver injury, and finally to alleviate the condition of T2DM with NAFLD. It may play a protective role in the damaged hepatic cells.

The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC