Methylamine and monensin do not block insulin internalization but do influence the intracellular distribution and action of insulin in pancreatic acini from diabetic mice.
Methylamine and monensin are two agents known to interfere with the recycling of membrane receptors. In the present investigation, we studied their effects on the binding, intracellular distribution, and action of insulin in isolated pancreatic acini prepared from diabetic mice. These drugs had several similar effects on these cells. In a dose-dependent fashion, both increased the amount of [125I]insulin associated with acini. Methylamine approximately doubled and monensin tripled the amount of insulin associated with cells. Employing electron microscope autoradiographs, we observed the accumulation of hormone in large vacuoles in the Golgi-lysosomal area after treatment with methylamine and in smaller swollen Golgi vesicles after treatment with monensin. The influences of both agents on the biological effects of insulin in acini were then investigated. Both agents blocked insulin stimulation of [3H]2-deoxy-D-glucose uptake in acini. The effect of methylamine was also studied on [3H]leucine incorporation into protein and was found to only partially block the effect of insulin. Since insulin and its receptor are internalized, it is likely that the accumulation of insulin in acini induced by these two agents was due to their inhibition of the cellular processing of insulin and its receptor. Moreover, the effects of these two agents to inhibit insulin-stimulated glucose transport may have resulted from either the inhibition of the recruitment of glucose carriers from the Golgi to the plasma membrane or an abnormal interaction of internalized insulin with the Golgi.
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005663:Furans / Q000494:pharmacology*; D006056:Golgi Apparatus / Q000378:metabolism; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007930:Leucine / Q000378:metabolism; D008297:Male; D008744:Methylamines / Q000494:pharmacology*; D051379:Mice; D008854:Microscopy, Electron; D008985:Monensin / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D014617:Vacuoles / Q000378:metabolism
D005663:Furans; D007328:Insulin; D008744:Methylamines; D008985:Monensin; D003847:Deoxyglucose; C027451:methylamine; D007930:Leucine