Aloperine Relieves Type 2 Diabetes Mellitus via Enhancing GLUT4 Expression and Translocation

Abstract

Aloperine (ALO), a quinolizidine alkaloid isolated from Sophora alopecuroides L. used in the traditional Uygur medicine, induced a significant increase in cellular glucose uptake of L6 cells, suggesting it has the potential to relieve hyperglycemia. Therefore, we investigated the effects of ALO on type 2 diabetes mellitus (T2DM) through in vitro and in vivo studies. The translocation of glucose transporter 4 (GLUT4) and changes in intracellular Ca2+ levels were real-time monitored in L6 cells using a laser scanning confocal microscope and related protein kinase inhibitors were used to explore the mechanism of action of ALO. Furthermore, high fat diet combined with low-dose streptozotocin (STZ) was used to induce T2DM in rats, and ALO was given to the stomach of T2DM rats for 4 weeks. In vitro results showed that ALO-induced enhancement of GLUT4 expression and translocation were mediated by G protein-PLC-PKC and PI3K/Akt pathways and ALO-enhanced intracellular Ca2+ was involved in activating PKC via G protein-PLC-IP3R-Ca2+ pathway, resulting in promoted GLUT4 plasma membrane fusion and subsequent glucose uptake. ALO treatment effectively ameliorated hyperglycemia, glucose intolerance, insulin resistance and dyslipidemia, alleviated hepatic steatosis, protected pancreatic islet function and activated GLUT4 expression in insulin target tissues of T2DM rats. These findings demonstrated that ALO deserves attention as a potential hypoglycemic agent.

Glucose Uptake Is Increased by Estradiol Dipropionate in L6 Skeletal Muscle Cells

“…The rising extracellular Ca 2+ level led to in 2-fold increases in GLUT4 expression in L6 myocytes and insulin stimulated glucose uptake [ 35 ]. It has been showed in the literature that the intracellular Ca 2+ plays a significant role in insulin induced GLUT4 transduction [ 29 , 36 ] and uptake of glucose [ 37 ]. EDP stimulated GLUT4 expression and intracellular Ca 2+ level ( Figure 5 A).…”

Aloperine protects against cerebral ischemia/reperfusion injury via activating the PI3K/AKT signaling pathway in rats

“…Animals in the positive control group received intraperitoneal administration of 2 mg/kg NIM (Shandong Fangming Pharmaceutical Group Co., Ltd.) instead of ALO, while those in the sham group received the same volume of saline (containing 10% acetic acid). The doses of ALO were determined based on previous studies ( 14 , 15 ). NIM is a dihydropyridine calcium antagonist, which can reduce nerve cell apoptosis through calcium influx, increase the oxygen supply and blood supply to brain tissue by improving the deformability of red blood cells, reducing the permeability of the blood-brain barrier and improving blood rheology, so as to protect cerebrovascular and nerve cells ( 16 , 17 ).…”

Triterpenoid saponins and C21 steroidal glycosides from Gymnema tingens and their glucose uptake activities

“…We used a cell-based uorescentlylabeled deoxyglucose analog kit (2-NBDG kit, Cayman Chemical, USA) to evaluate whether compounds 1-11 increased glucose uptake in L6 cells. 49,50 Before the experiment, the differentiated L6 myotube was inoculated into a 96-well plate at a density of 1 × 10 4 -4 × 10 4 cells/well. Aer 2 h of starvation in serum-free a-MEM medium, we add 100 mL MEM-a medium, which contained different drugs, to each well, and cells were incubated for 12 h to 100% fusion.…”