The transport of alanine by system A is an important source of carbons for the synthesis of glucose in the liver. Here, we show that the mRNA encoding the ubiquitously expressed isoform of the rat system A transporter (SAT2) is dramatically increased in liver following streptozotocin-induced diabetes. This increase in SAT2 mRNA is intensified in the gluconeogenic periportal hepatocytes and also in hepatocytes surrounding the central vein. SAT3, the more abundant system A mRNA isoform present in liver, is restricted to perivenous hepatocytes and is also increased following this treatment but to a much lesser extent than SAT2 mRNA. SN1, an abundant system N mRNA isoform expressed in both perivenous and periportal hepatocytes, is not affected by streptozotocin treatment. A pharmacological dose of glucagon also increased both SAT2 and SAT3 mRNA levels in liver while SN1 mRNA levels remained unaffected. These results indicate that the increase in system A activity observed in liver following experimentally induced diabetes or glucagon treatment is due to the selective increase in mRNAs encoding system A transporters. (C) 2002 Elsevier Science (USA).