Mechanism Of Catalpol Regulation Of AMPK/GLUT4 Signaling Pathway In Skeletal Muscle Of Rats With Type 2 Diabetes

Objective: To examine how catalpol affects type 2 diabetic rats’ fasting blood sugar(FBG),fasting insulin(FINS),insulin sensitivity index(ISI),and control of the AMPK/GLUT4 signaling pathway.Methods: The Experimental Animal Center of Heilongjiang University of Traditional Chinese Medicine provided 100 healthy male Wistar rats aged 8weeks and weighing 150 ± 50 g.After one week of adaptive feeding,the rats were divided into two groups: normal(n = 10)and experimental(n = 90).For8 weeks,the rats in the experimental group were fed a diet heavy in sugar and fat while the rats in the control group were fed a regular diet.Streptozotocin(STZ,15 mg/kg)was administered intraperitoneally to the rats in the experimental group after they had fasted for 12 hours.Sixty rats that successfully modeled were divided into five groups at random,each with 12rats: the model group,the control group,the low-dose catalpol group,the middle-dose catalpol group,and the high-dose catalpol group.Five milliliters per kilogram of distilled water was gavaged daily to the rats in the normal group and the model group.The rats in the control group received daily gavage administration of 90 mg/kg metformin.Catalpol was gavaged into the stomachs of the rats in the low,medium,and high dose groups at doses of 2.5mg/kg,5 mg/kg,and 10 mg/kg every day.The general health of the rats in each group was noted after 12 weeks of intragastric intervention,and the fasting blood sugar,fasting serum insulin,and insulin sensitivity index were all calculated.By using immunohistochemistry to detect AMPK and GLUT4 protein expression,and RT-PCR to detect AMPK and GLUT4 gene expression in skeletal muscle.By using a Western blot,the expression of the p-AMPK、AMDK protein was found.At last,the data were examined using SPSS 26.0statistical software.Results: Compared with the normal group,the levels of FBG and FINS in the model group were significantly increased(p < 0.05 or p < 0.01),and ISI was significantly decreased(p < 0.05 or p < 0.01).At the same time,compared with the model group,the levels of FBG and FINS in the catalpol group were also significantly decreased(p < 0.05 or p < 0.01).Compared with the control group,there was no significant difference in FBG and ISI levels in the high-dose catalpol group(p > 0.05).The level of FBG in catalpol middle dose group was significantly higher(p < 0.05),and there was significant difference in ISI level(p < 0.05).The results of immunohistochemistry showed that the expression of AMPK and GLUT4 was the highest in the normal group,and the other groups had different degrees of expression.Compared with the metformin control group,the high-dose catalpol group was better than the metformin control group(p < 0.05).The AMPK gene was expressed in all groups,but there was no significant difference between the groups(p > 0.05).Western blot results showed that compared with the normal group,the ratio of p-AMPK / AMPK protein in skeletal muscle of rats in other groups decreased(p < 0.05).Compared with the model group,the ratio of p-AMPK / AMPK protein in the skeletal muscle of the metformin group,catalpol low,medium and high dose groups increased,and the ratio of p-AMPK / AMPK protein in catalpol high dose group was significantly different from that in other groups(p < 0.05).Conclusion:1.In type 2 diabetic rats,catalpol can improve glucose metabolism abnormality,lower fasting blood glucose,and maintain glucose metabolism equilibrium.2.In type 2 diabetic rats,catalpol can increase insulin sensitivity.3.In rat skeletal muscle,catalpol can control the AMPK/GLUT4 signaling pathway,improve AMPK/GLUT4 protein expression,and lessen insulin resistance in type 2 diabetic rats.