Abstract: OBJECTIVE:To observe the effect of Jiangtang Xiaoke(JTXK) granule on endoplasmic reticulum(ER)stress in high fat diet(HFD)-induced type 2 diabetes mellitus(T2 DM) KK-Ay mice.METHODS:KK-Ay mice were fed with HFD to induce the T2 DM model,while normal control C57 BL/6 J mice were given standard feed.Fasting blood glucose(FBG) in all mice was measured weekly and oral glucose tolerance tests(OGTTs) were performed at 4 and 10 weeks after start of treatment to determine glucose metabolism.Serum fasting insulin(FINS) and insulin sensitivity index(ISI) were measured to determine insulin sensitivity.m RNA expressions of eukaryotic initiation factor-2 alpha(e IF2α),glucose regulated protein 78(GRP78),activating transcription factor 4(ATF4),and C/EBP homology protein(CHOP) were assessed by reverse transcription polymerase chain reaction and the protein expressions of p-e IF2α,GRP78,and CHOP were assessed by Western blotting.RESULTS:JTXK granule significantly reduced FBG and free fatty acid levels and improved OGTT at the120 min of the 10-week treatment in T2 DM KK-Ay mice.FINS and Hb Alc levels were reduced and insulin sensitivities were increased in KK-Ay diabetic mice,which were improved with the treatment of JTXK granule,especially at the 7 and 3.5 g/kg doses.JTXK granule at the 3.5 g/kg dose was most effective in reducing both gene and protein expressions of e IF2α,GRP78,and CHOP.CONCLUSION:ER stress response is increased in T2 DM KK-Ay mice.Treatment with JTXK granule attenuates glucose disorders,improves insulin sensitivity,and reduces serum FFA in T2 DM KK-Ay mice.The mechanisms may be attributed to regulation of the signaling ER stress pathway via decreasing e IF2α phosphorylation and suppressing e IF2α-ATF4-CHOP activation.

Key words: Endoplasmic reticulum stress, Fatty liver Lipid metabolism, Diabetes mellitus,type 2, Jiangtang Xiaoke granule