Guanine nucleotide binding regulatory proteins and adenylate cyclase in livers of streptozotocin- and BB/Wor-diabetic rats. Immunodetection of Gs and Gi with antisera prepared against synthetic peptides.
Adenylate cyclase in liver plasma membranes from streptozotocin-diabetic (STZ) or BB/Wor spontaneously diabetic rats showed increased responsiveness to GTP, glucagon, fluoroaluminate, and cholera toxin. Basal or forskolin-stimulated activity was unchanged in STZ rats, but increased in BB/Wor rats. No change in the alpha-subunit of Gi (alpha i) was observed in STZ or BB/Wor rats using pertussis toxin-stimulated [32P]ADP-ribosylation. Immunodetection using antibodies against the COOH-terminal decapeptides of alpha T and alpha i-3 showed no change in alpha i in STZ rats and a slight decrease in BB/Wor rats. Angiotensin II inhibition of hepatic adenylate cyclase was not altered in either diabetic rat. In both models of diabetes, Gs alpha-subunits were increased as measured by cholera toxin-stimulated [32P]-ADP-ribosylation of 43-47.5-kD peptides, reconstitution with membranes from S49 cyc- cells or immunoreactivity using antibodies against the COOH-terminal decapeptide of alpha s. These data indicate that STZ-diabetes increases hepatic Gs but does not change Gi or adenylate cyclase catalytic activity. In contrast, BB/Wor rats show increased hepatic Gs and adenylate cyclase. These changes could explain the increase in hepatic cAMP and related dysfunctions observed in diabetes.
Lynch
C J
CJ
Howard Hughes Medical Institute, Vanderbilt University, Nashville, Tennessee 37232.
Blackmore
P F
PF
Johnson
E H
EH
Wange
R L
RL
Krone
P K
PK
Exton
J H
JH
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000302:isolation & purification* / Q000378:metabolism; D000535:Aluminum / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002384:Catalysis; D002460:Cell Line; D002462:Cell Membrane / Q000032:analysis; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005461:Fluorine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000302:isolation & purification*; D005934:Glucagon / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007106:Immune Sera; D007274:Injections, Intraperitoneal; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology*; D037342:Pertussis Toxin; D051381:Rats; D011913:Rats, Inbred BB; D011919:Rats, Inbred Strains; D010566:Virulence Factors, Bordetella / Q000008:administration & dosage
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D007106:Immune Sera; D010446:Peptide Fragments; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D005576:Colforsin; D000246:Adenosine Diphosphate Ribose; C053629:fluoroaluminum; D005461:Fluorine; D006160:Guanosine Triphosphate; D005934:Glucagon; D002772:Cholera Toxin; D000535:Aluminum; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases