Specific macrophage receptor activity for advanced glycosylation end products inversely correlates with insulin levels in vivo.
A high-affinity macrophage receptor has been shown to mediate the removal of proteins modified by advanced nonenzymatic glycosylation end products (AGEs) in both animals and humans. To characterize the effect of diabetes on this receptor system, resident peritoneal macrophages from experimentally induced and genetically diabetic mice were studied. Binding and degradation of radioiodinated AGE-bovine serum albumin (AGE-BSA) were determined from saturation kinetics and compared with glucose and insulin levels of each subgroup. Scatchard plot analysis of nondiabetic mouse macrophages has indicated 1.5 X 10(5) receptors/cell, with a binding affinity of 1.7 X 10(7) M-1. The in vitro exposure of macrophages to either elevated glucose or insulin concentrations failed to demonstrate a short-term regulatory effect on AGE-receptor function. However, macrophages from hypoinsulinemic alloxan-induced diabetic mice indicated a two- to threefold increase in AGE-receptor number per cell (2.98 +/- 0.25 X 10(5)/cell), and macrophages from C57BL/KsJ (db/db) mice showed an almost threefold greater receptor number (2.86 +/- 0.2 X 10(5)/cell), with binding affinity remaining essentially unchanged (1.24 +/- 0.05 X 10(7) and 1.21 +/- 0.07 X 10(7) M-1, respectively). In addition, a moderate increase (25-30%) of 125I-labeled AGE-BSA degradation was observed in these two insulin-deficient diabetic macrophage groups compared with the normal control group. In contrast, macrophages from hyperinsulinemic and hyperglycemic C57BL/6J (db/db) mice demonstrated a distinct reduction in both AGE-receptor number (0.67 +/- 0.03 X 10(5)/cell) and binding affinity (0.37 +/- 0.03 X 10(7) M-1), with a decrease of AGE-BSA degradation of approximately 50% compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Vlassara
H
H
Laboratory of Medical Biochemistry, Rockefeller University, New York, NY 10021.
Brownlee
M
M
Cerami
A
A
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006031:Glycosylation; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*
D007328:Insulin; D011506:Proteins; D011956:Receptors, Cell Surface; C027786:glucose receptor; D005947:Glucose