Selective up-regulation of system a transporter mRNA in diabetic liver.
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.
Varoqui
Hélène
H
Department of Opthalmology, Louisiana State University Health Sciences Center, New Orleans, Louisiania 70112, USA.
Erickson
Jeffrey D
JD
D026924:Amino Acid Transport System A / Q000096:biosynthesis* / Q000235:genetics; D026921:Amino Acid Transport Systems, Neutral; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005934:Glucagon / Q000494:pharmacology; D022781:Hepatocytes / Q000378:metabolism; D017403:In Situ Hybridization; D008099:Liver / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D015533:Transcriptional Activation; D015854:Up-Regulation
D026924:Amino Acid Transport System A; D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C412568:Slc38a2 protein, rat; C403222:system N protein 1; D005934:Glucagon