Acarbose attenuates migration/proliferation via targeting microRNA-143 in vascular smooth muscle cells under diabetic conditions

Abstract

Acarbose (an a-glucosidase inhibitor) has been demonstrated to reduce the progression of atherosclerosis without affecting serum levels of glucose in rabbits fed a high cholesterol diet. The main focus of recent atherosclerosis studies has been microRNA targets. However, the mechanism by which acarbose targets miRNA-mediated atherosclerosis remains unclear. This study aimed to evaluate the effect of acarbose on microRNA-related regulation of rat aortic vascular smooth cell line (A7r5 cell) migration and proliferation induced by diabetic conditions. We reported that acabose exhibit significantly inhibits proliferative and cell migration abilities in A7r5 cells. The expression of protein and levels of mRNA were measured by Western blot analysis and real-time PCR. Acarbose inhibited the phosphorylation of focal adhesion kinase (FAK) and phosphoinositide 3-kinases (PI3K)/protein kinase B (Akt), Ras signals, small GTPase proteins expression to attenuate cell migration and proliferation. Furthermore, acarbose upregulated the expression of miR-143, and transfected miR-143 mimic and its inhibitor to explore its mechanism. In conclusion, acarbose reduces VSMC migration and proliferation via upregulating miR-143 to inhibit Ras-related signaling, and potentially prevention of atherosclerosis.

Effect of delayed luminal carbodhydrate uptake via α-glucosidase inhibition on plasma glycemic parameters and lipid profiles in adult wistar fatty rats

“…In clinical trials lasting 12weeks or more, the HbA1c and glycemic responses typically demonstrated improvement over time while lipid profiles while improved, were less dramatic. [18][19][20][21][22][23][24][25][26][27][28][29] The results of this study are consistent with previous clinical findings, and confirm that the 8-week trial of feeding a highly palatable high carbohydrate sucroseladen diet to both lean and obese adult Wistar Fatty Rats with wellestablished NIDDM in the obese phenotype resulted in excess weight gain in both phenotypes, with the greatest gain by far among the obese+NIDDM phenotype. The SU diet also was associated with a predictable exaggeration of glycemic responses in the obese+NIDDM phenotype.…”

“…13 The lipid profiles in the obese+NIDDM phenotype have been associated with increases in biochemical markers for free radical development and are clearly consistent with atherogenic lipid profiles, including elevations in both serum triglycerides and cholesterol, including the Low density (Alpha) lipoprotein fraction which have been associated with senescent alterations in the vascular intima. [29][30][31] Although the lipid parameters were not remarkably improved in the obese+NIDDM rats following the ACB treatment, the excess weight gain of obese+NIDDM rats consuming the high sucrose diet was improved, suggesting relatively short duration of the therapeutic regimen may have been effective in attenuating the glycemic status, with some improvement in insulin sensitivity, but the normalization of the lipid profiles may require a longer treatment duration or a greater dose of the α-glucosidase inhibitor agent. In contrast, acarbose was effective in improving both glycemic and lipid parameters and in normalizing weight gain with the SU diet to that of ST fed controls.…”

“…17,18 Thus, long term treatment with α-glucosidase inhibitors especially when combined with dietary intervention can bring about long term improvements in both glycemic and lipid profiles, and a likely decreased rate of progression of NIDDM and atherogenic markers of cardiovascular disease and senescence. [22][23][24][25][26][27][28][29][30][31] Thus, the α-glucosidase competitive inhibitor Acarbose has been evaluated in several short to medium length clinical studies where it has been found to result in statistically significant improvements in glycemic parameters in NIDDM, including improvement in blood glucose and HbA1c levels when used as monotherapy in conjunction with dietary modification. Most studies have reported beneficial effects after 12 or more weeks administration of a dose of 50 to 100 mg before meals.…”

“…Most studies have reported beneficial effects after 12 or more weeks administration of a dose of 50 to 100 mg before meals. [22][23][24][25][26][27][28][29] In contrast, the effects of acarbose on lipid parameters have been variable, likely due to differences in patient populations, duration of pre-existing illness, dosages employed, and duration of treatment, and are likely attributable to an improved economy of insulin sensitivity and glucose utilization in peripheral tissues.…”

Mulberry Leaf and Neochlorogenic Acid Alleviates Glucolipotoxicity-Induced Oxidative Stress and Inhibits Proliferation/Migration via Downregulating Ras and FAK Signaling Pathway in Vascular Smooth Muscle Cell

“…A previous in vitro study suggested that in tumor cell lines, osteopontin stimulates MMP9 up-regulation via FAK, ERK, and NF-κB-dependent signaling pathways, which promote cytoskeletal organization, cell motility, and cell migration [ 12 ]. Furthermore, our previous study showed that diabetic conditions (OH) induced A7r5 cell migration and proliferation-related signaling and that acarbose treatment could potentially prevent atherosclerosis [ 13 ].…”