Tangzhiqing enhances glucose and lipid metabolism in obese diabetic rats by targeting PI3K/AKT and ER stress.

INTRODUCTION: The study determined the influence of the Tangzhiqing formula (TZQ) on insulin resistance in obese rats having type 2 diabetes mellitus (T2DM). The investigation was performed for the PI3K/AKT signaling pathway and endoplasmic reticulum (ER) stress. METHODS: The study consists of 48 Sprague-Dawley rats, which were given a high-fat diet for 4 weeks. These rats were also injected with streptozotocin (STZ) to develop obesity and T2DM mellitus (T2DM). The sample was distributed into 6 different groups, including the model group, control group, the low dose of TZQ (TZQ1), the medium dose of TZQ (TZQ2), the high dose of TZQ (TZQ3), and the metformin group, having 8 rats in each group. After a 4-week treatment period, measurements were performed for serum fasting blood glucose (FBG), fasting insulin (FINS), insulin resistance (HOMA-IR), insulin sensitivity index (ISI), and lipid profiles. HE staining, RT-qPCR, and western blotting were utilized for analyzing pancreatic tissues. Further, the examination of the PI3K/AKT signaling and the proteins associated with ER stress was performed. RESULTS: TZQ revealed a significant decline in FBG, FINS, and HOMA-IR. A noteworthy improvement in ISI was reflected in TZQ2 and TZQ3. TZQ reduced TG, TC, LDL-C, and FFA levels. However, TZQ increased HDL-C. In TZQ1, TZQ2, and TZQ3, pancreatic islet cell injury had been reduced. TZQ raised PI3K, AKT mRNA, and protein expression and decreased ERK, IRE1, GRP78, and ATF6. DISCUSSION: TZQ modified the PI3K/AKT pathway and ER stress. This experiment has identified possible therapeutic advantages of TZQ for handling T2DM. The insulin resistance was enhanced, and glucose and lipid metabolism were improved amongst the rats with obesity and T2DM when given TZQ.