Impaired glucose tolerance and increased weight gain in transgenic rats overexpressing a non-insulin-responsive phosphoenolpyruvate carboxykinase gene

Abstract

The effects of an overexpressed, non-insulin-responsive gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (GTP) (PEPCK; EC 4.1.1.32), on glucose homeostasis were investigated. Transgenic rats harboring a metallothionein-driven PEPCK gene (lacking the entire PEPCK upstream- regulatory region) expressed transgene PEPCK mRNA in the key gluconeogenic tissues, liver and kidney. Female transgenic rats, studied at 10 weeks of age, showed mild fasting hyperglycemia (6.9 ± 0.2 vs. 5.9 ± 0.1 mM P = 0.002 n = 6), hyperinsulinemia (92.2 ± 4.0 vs. 54.0 ± 6.6 pM, P = 0.001, n = 6), impaired glucose tolerance and increased weight gain (178.3 ± 3.2 vs. 153.4 ± 2.5 g, P = 0.001, n = 16 and n = 13 trans..