THE FUNCTION BUT NOT THE EXPRESSION OF RAT-LIVER INHIBITORY GUANINE-NUCLEOTIDE BINDING-PROTEIN IS ALTERED IN STREPTOZOTOCIN-INDUCED DIABETES

Adenylate cyclase activity was examined as a measure of inhibitory guanine nucleotide binding protein (G(i)) function in liver plasma membranes from rats made chemically diabetic by streptozotocin (STZ) treatment. Clonidine activation of the alpha-2 adrenergic receptor, which activates G(i), inhibited forskolin-stimulated adenylate cyclase activity in control membranes. However, there was no effect on adenylate cyclase activity in membranes from STZ diabetic animals. Also, a polyclonal antipeptide antibody was raised to a highly conserved segment of the G(i)-alpha-2 subunit. This antibody specifically recognizes a 41 kilodalton protein, is blocked by an excess of peptide, does not recognize the alpha-subunit of transducin, and immunoprecipitates a 41 kilodalton protein which was ADP-ribosylated by pertussis toxin. Immunoblots using this antibody detect no difference between normal and STZ diabetic animals in the level of liver plasma membrane G(i) expression. Therefore, STZ-induced diabetes altered the function of G(i) but had no effect on G(i) expression.