Influence of streptozotocin-induced diabetes on adenylate cyclase activity in cultured type II pneumocytes.
Previous studies with cultured type II pneumocytes from streptozotocin-induced diabetic rats demonstrated altered surfactant synthesis and secretion. The effects of the diabetic state were reversed by in vivo but not in vitro insulin treatment. In the current study, cultured type II pneumocytes from control and streptozotocin-induced diabetic rats were demonstrated to possess approximately 17,500 and 8,500 receptors per cell, respectively. High-affinity binding sites were determined to have a dissociation constant of 0.429 nM and 0.203 nM for control and diabetic cells, respectively. Functional capacity of the insulin receptors was determined by the initial rates of 2-deoxy-D-glucose uptake. Uptake was stimulated by insulin in a dose-dependent manner and was not significantly altered by the diabetic state. This would suggest that the insulin receptor was present and functioning in cells isolated from diabetic rats. Basal adenylate cyclase activity of type II cell homogenates from diabetic rats was shown to be 16% of that for controls. In addition, isoproterenol, guanosine 5'-triphosphate (GTP), and NaF were unable to stimulate adenylate cyclase activity. However, forskolin, which directly activates the catalytic subunit of adenylate cyclase, was able to increase the cellular content of cyclic adenosine monophosphate (cAMP) in this model. This would suggest that some step prior to adenylate cyclase but not the catalytic subunit was altered by the diabetic state. But forskolin was unable to restore surfactant secretion, suggesting that in addition to adenylate cyclase, other processes are affected by the diabetic state. The effects of the diabetic state on adenylate cyclase and surfactant secretion were reversed by in vivo but not in vitro insulin treatment.
Brown
L A
LA
Department of Pediatrics, Emory University, Atlanta, Georgia 30322.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D011663:Pulmonary Surfactants / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism; D012969:Sodium Fluoride / Q000494:pharmacology; D013311:Streptozocin
D007328:Insulin; D011663:Pulmonary Surfactants; D005576:Colforsin; D013311:Streptozocin; D006160:Guanosine Triphosphate; D012969:Sodium Fluoride; D003847:Deoxyglucose; D000242:Cyclic AMP; D011972:Receptor, Insulin; D000262:Adenylyl Cyclases; D007545:Isoproterenol