LAUSR

Abstract 1. The metformin and Scutellariae radix extract (SB) combination has been previously reported to enhance anti-diabetic activity. Considering that organic cation transporters (OCTs) and multi-drug and toxin extrusion proteins (MATEs) in the liver and kidney are determinant factors on hepatic distribution and renal clearance of metformin, the effects of SB on OCT or MATE-mediated systemic exposure of metformin as well as on glucose tolerance and hypoglycemia were examined. 2. Although SB inhibited metformin uptake through human transporters OCT1 and MATE1 in vitro, the systemic exposures of metformin in vivo rats were not altered after metformin treatment with and without SB due to unchanged renal excretion of metformin. 3. However, 28-day metformin treatment with SB decreased the mRNA level of hepatic MATE1 in rats, resulting in reduced biliary excretion of metformin and thereby higher concentration of metformin in the liver. In addition, in rats with 28-day metformin treatment with SB, glucose tolerance and plasma lactate level were enhanced, while hypoglycemia was not detected. 4. Thus in rats, intervention of SB on transporter-mediated metformin transportation partially improves glucose tolerance without hypoglycemia and increases hepatic distribution of metformin. Also the further investigations in humans are required to clarify the relevance of these findings to the clinical significance.