INCREASED ALANINE UPTAKE AND LIPID-SYNTHESIS FROM ALANINE IN ISOLATEDHEPATOCYTES OF WISTAR-KYOTO FATTY RATS - AN INHIBITORY EFFECT OF BIGUANIDES

To examine the pathophysiological characteristics of non-insulin-depen dent diabetes mellitus, alanine metabolism in isolated hepatocytes of male Wistar-Kyoto (WKY) fatty rats (genetically obese and hyperglycemi c) and their lean littermates was investigated. The effects of glucago n and the biguanides, metformin and buformin, on alanine metabolism we re also studied by measuring alanine uptake and lipid synthesis from a lanine. WKY fatty rats showed higher plasma insulin and lipid concentr ations than lean rats at 5 as well as at 12 weeks of age. Alanine upta ke into hepatocytes was increased in fatty rats only at 12 weeks of ag e compared with lean rats. Lipid synthesis from alanine in hepatocytes was increased in fatty rats at 5 and 12 weeks of age compared with le an rats. Glucagon increased alamine uptake into hepatocytes but did no t affect lipid synthesis from alanine in both fatty and lean rats. Low concentrations (0.1 mM) of biguanides decreased lipid synthesis from alanine only in fatty rats without inhibiting alanine uptake into hepa tocytes. These observations suggest that lipid synthesis from alanine in hepatocytes of WKY fatty rats is accelerated prior to the onset of diabetes mellitus, which might be associated with the development of d iabetes, and that an inhibitory effect on increased lipid synthesis is one of the pharmacodynamic actions of biguanides.