Natural diterpenoid alysine A isolated from Teucrium alyssifolium exerts antidiabetic effect via enhanced glucose uptake and suppressed glucose absorption

Authors: ALAATTİN ŞEN, BUKET AYAR, ANIL YILMAZ, ÖZDEN ÖZGÜN ACAR, GURBET ÇELİK TURGUT, GÜLAÇTI TOPÇU

Abstract: Teucrium species have been used in folk medicine as antidiabetic, antiinflammatory, antiulcer, and antibacterial agents. We have explored in vitro antidiabetic impacts of 2 natural diterpenoids, alysine A and alysine B, isolated from Teucrium alyssifolium. The lactate dehydrogenase (LDH) cytotoxicity assay, glucose uptake test, glucose utilization (glycogen content) test, glucose transport test, glucose absorption ($\alpha $-glucosidase activity) test, insulin secretion test, RNA isolation and cDNA synthesis assay, qPCR quantification assays, and statistical analyses were carried out in the present study. Alysine A exerted the following effects at non-cytotoxic doses: . Enhanced the glucose uptake, as much as the insulin in the C2C12, HepG2, and 3T3-L1 cells . Increased the glycogen content in the C2C12 and HepG2 liver cells, significantly higher than the insulin and metformin . Suppressed the alpha-glucosidase and the GLUT2 expression levels in the Caco-2 cells . Suppressed the SGLT1 and GLUT1-5 expression levels in the Caco-2 cells . Induced the insulin receptor substrate (IRS)1 and GLUT2 expression levels of the BTC6 pancreatic cells . Induced the insulin receptor (INSR), IRS2, phosphoinositide 3-kinase (PI3K), GLUT4, and protein kinase (PK) expression levels of the 3T3-L1 and C2C12 cells .Increased glucose transport through the Caco-2 cell layer . Did not influence insulin secretion in the pancreatic BTC6 cells Consequently, these data strongly emphasized the antidiabetic action of alysine A on the particularly critical model mechanisms that assume a part in glucose homeostasis, such as glucose uptake, utilization, and storage. Moreover, the expression level of the essential genes in glucose metabolism and insulin signaling was altered in a way that the results would be antihyperglycemic. A blend of in vitro and in situ tests affirmed the antihyperglycemic action of alysine A and its mechanism. Alysine A has exercised significant and positive results on the glucose homeostasis; thus, it is a natural and pleiotropic antidiabetic agent. Advanced in vivo studies are required to clarify the impact of this compound on glucose homeostasis completely.

Keywords: Alysine A, alysine B, antidiabetic, Teucrium alyssifolium, glucose homeostasis

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