Alteration in pancreatic immunoreactivity of insulin-like growth factor (IGF)-binding protein (IGFBP)-6 and in intracellular degradation of IGFBP-3 in fibroblasts of IGF-II receptor/IGF-II-deficient mice.
The Type-2 insulin-like growth factor receptor (IGF2R) mediates the transport of lysosomal hydrolases to lysosomes and the clearance of insulin-like growth factor II (IGF-II). Mutant mice lacking IGF2R usually die perinatally, but are completely rescued from lethality in the absence of IGF-II. IGF2R/IGF-II-deficient mice have elevated levels of circulating IGF binding protein (IGFBP)-3 and show a strong IGFBP-6 immunoreactivity in all pancreatic islet cells and in secretory granules of different size in acinar cells and interlobular connective tissue of exocrine pancreas. Fibroblasts derived from double mutant mice missort the lysosomal protease cathepsin D, and are able to degrade endocytosed (125I)IGFBP-3 intracellularly, however, with lower efficiency than in control cells. These results show that the deficiency of IGF2R and IGF-II affects the expression and metabolism of IGFBPs in a tissue- and cell type-specific manner.
Braulke
T
T
Institute for Biochemistry II, University of Göttingen, Germany. braulke ukb2-00.uni-bc.gwdg.de
Dittmer
F
F
Götz
W
W
von Figura
K
K
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015153:Blotting, Western; D002402:Cathepsin D / Q000032:analysis; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004705:Endocytosis / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D051907:Lysosomal Membrane Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D010179:Pancreas / Q000737:chemistry* / Q000166:cytology; D011233:Precipitin Tests; D017527:Receptor, IGF Type 2 / Q000032:analysis / Q000235:genetics* / Q000276:immunology
D015703:Antigens, CD; D017077:Culture Media, Conditioned; D018972:Insulin-Like Growth Factor Binding Protein 3; D018976:Insulin-Like Growth Factor Binding Protein 6; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II; D002402:Cathepsin D