Endocytosis is inhibited in hepatocytes from diabetic rats.
The consequences of type I diabetes on cellular endocytosis were investigated by comparing [125I]insulin, [125I]alpha 2-macroglobulin, and Lucifer yellow uptake in hepatocytes freshly isolated from control and STZ-induced diabetic rats. In addition to the previously described reversible inhibition of ligand-induced internalization of the insulin receptor, we report a decrease in the constitutive receptor-mediated endocytosis of alpha 2-macroglobulin and a near abolition of fluid-phase endocytosis of Lucifer yellow in cells from diabetic animals. Despite decreased receptor autophosphorylation and internalization, the ligand-induced surface redistribution of the insulin receptor was normal in the diabetic cell population. By contrast, the insulin receptor association with clathrin-coated pits was impaired in diabetic cells as a result of a decreased concentration of these specialized invaginations on the nonvillous cell surface. The morphology and diameter of clathrin-coated pits were similar in both conditions under study. These results demonstrate a general impairment of endocytosis in hypoinsulinemic diabetes: receptor-mediated endocytosis was less affected than fluid-phase endocytosis. Impaired endocytosis of specific ligands or other macromolecules could be an important mechanism underlying the accumulation of extracellular matrix or even blood cholesterol removal in diabetes.
Krischer
J
J
Department of Morphology, University of Geneva Medical School, Switzerland.
Gilbert
A
A
Gorden
P
P
Carpentier
J L
JL
D000818:Animals; D002966:Clathrin; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D004705:Endocytosis / Q000502:physiology*; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007328:Insulin / Q000493:pharmacokinetics; D007546:Isoquinolines / Q000493:pharmacokinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000493:pharmacokinetics
D002966:Clathrin; D005456:Fluorescent Dyes; D007328:Insulin; D007546:Isoquinolines; D000511:alpha-Macroglobulins; C017475:lucifer yellow; D011972:Receptor, Insulin