The effect of anti-insulin IgG (AlAb) on the ultrastructural organization of insulinreceptors on liver and adipocyte plasma membranes was studied using monomeric ferritin-insulin (Fm-I) as an electron microscopic marker for the insulin binding sites. Liver plasma membranes wereincubated at 0°C and 24°C with 250, 500, or 1000 μU monomeric Fm-I/ml, in the presence and absence of AlAb at a concentration that tripled 125I-insulin binding to livermembranes. Electron microscopy revealed that increasing concentrations of Fm-I increased the number of occupied receptors but had no effect on the distribution of occupied receptors into groups of various sizes on liver membranes. Over 60% of the receptors were observed as single molecules. At 24°C, AlAb produced a significant aggregation of occupied receptors, and only 30% of the receptors were found as single sites. At 0°C, AlAb hardly affected receptor distribution. On adipocyte membranes, however, about 60% of the occupied receptors normally occurred in groups of 2–6 molecules. Addition of AlAb to the adipocyte membranes, at concentrations just below that which inhibited 125I-insulin binding to these membranes, had no effect on the distribution pattern of Fm-I occupied receptors. Normal IgG had no effect on the Fm-I occupied receptors on either liver or adipocyte membranes. These data show that Fm-I occupied receptor sites on liver membranes at 24°C are mobile, and that insulin itself did not cause grouping of these receptors. AlAb-induced Fm-I aggregation probably occurred as the bivalent antibody cross-linked the occupied mobile receptors, since AlAb could not cause aggregation on liver membranes at 0°C, when the receptors were less mobile. The AlAb does not have a morphologically demonstrable effect on the already grouped receptor sites on adipocytes. Insulin receptors on liver and adipocyte membranes differ, not only in their organizational pattern, but also in their responses to AlAb, suggesting that unique differences exist between the membranes, the receptors in the membranes, or both.
Differences in the Ability of Anti-Insulin Antibody to Aggregate Monomeric Ferritin-Insulin Occupied Receptor Sites on Liver and Adipocyte Plasma Membranes
Kenneth R Lyen, Robert M Smith, Leonard Jarett; Differences in the Ability of Anti-Insulin Antibody to Aggregate Monomeric Ferritin-Insulin Occupied Receptor Sites on Liver and Adipocyte Plasma Membranes. Diabetes 1 July 1983; 32 (7): 648–653. https://doi.org/10.2337/diab.32.7.648
Download citation file: