Anıl YILMAZ, Alaattin ŞEN, Buket AYAR, Gurbet Çelik TURGUT, Özden Özgün ACAR, Gülaçtı TOPÇU

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

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, isolatedfrom Teucrium alyssifolium. The lactate dehydrogenase (LDH) cytotoxicity assay, glucose uptake test, glucose utilization(glycogen content) test, glucose transport test, glucose absorption (α-glucosidase activity) test, insulin secretion test,RNA isolation and cDNA synthesis assay, qPCR quantification assays, and statistical analyses were carried out in thepresent 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 andmetformin• 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 cellsConsequently, these data strongly emphasized the antidiabetic action of alysine A on the particularly critical modelmechanisms that assume a part in glucose homeostasis, such as glucose uptake, utilization, and storage. Moreover, theexpression level of the essential genes in glucose metabolism and insulin signaling was altered in a way that the resultswould be antihyperglycemic. A blend of in vitro and in situ tests affirmed the antihyperglycemic action of alysine A andits mechanism. Alysine A has exercised significant and positive results on the glucose homeostasis; thus, it is a naturaland pleiotropic antidiabetic agent. Advanced in vivo studies are required to clarify the impact of this compound onglucose homeostasis completely.

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