Effect of insulin to decrease glucose transport in dissociated cells from the R3230AC mammary adenocarcinoma of diabetic rats.
Dissociated cells of the R3230AC mammary tumor were found to take up glucose by diffusion and by a passive carrier system. Using labeled 3-O-methylglucose as the probe, the following properties of the passive carrier were identified: (1) specificity for glucose, (2) competition by galactose and mannose but not by mannitol and fructose, (3) inhibition by phloretin but not by phloridzin, (4) temperature sensitivity, and (5) a Km for transport of 3-4 mM. The effects of insulin in vitro on carrier-mediated glucose transport were investigated in tumor cells from diabetic rats. At 10-9 M insulin, a time-related decrease in v for transport was observed resulting in an increased calculated Km (2- to 3-fold increase after 60-90 min incubation with insulin); only slight effects on V were obtained. This unusual response in v to insulin was observed when glucose was present in the medium at 2 mM and 5 mM, but not at 20 mM glucose. The effect of insulin to decrease the v was dose-related, with the major effects seen between 10-10M and 10-8M. The apparent decrease in glucose entry in vitro may in part explain the ability of insulin to inhibit growth of this tumor in vivo.
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000378:metabolism*; D004058:Diffusion; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D008757:Methylglucosides / Q000378:metabolism; D010693:Phloretin / Q000494:pharmacology; D051381:Rats; D013311:Streptozocin
D007328:Insulin; D008757:Methylglucosides; D013311:Streptozocin; D005947:Glucose; D010693:Phloretin