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 (Gi) function in liver plasma membranes from rats made chemically diabetic by streptozotocin (STZ) treatment. Clonidine activation of the alpha 2 adrenergic receptor, which activates Gi, 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 Gi 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 Gi expression. Therefore, STZ-induced diabetes altered the function of Gi but had no effect on Gi expression.
Allard
W J
WJ
Department of Molecular Biology, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486.
Vicario
P P
PP
Saperstein
R
R
Slater
E E
EE
Strout
H V
HV
D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D002462:Cell Membrane / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015151:Immunoblotting; D008099:Liver / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D051381:Rats
D005576:Colforsin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D003000:Clonidine