Abstract
The ability of insulin to bind, internalize, and regulate its own receptor was investigated in cultured human fibroblasts obtained from 8 normal subjects and 8 patients with type II, non-insulin-dependent diabetes mellitus (NIDDM). The ability of the cells from the two groups to bind insulin was the same, and Scatchard analysis demonstrated identical curvilinear plots. When cells were incubated at 37 degrees C with the lysosomotropic agent, chloroquine, and 125I-insulin, the drug led to a marked, but comparable, increase in cell-associated radioactivity in both control and diabetic fibroblasts (236 and 245% increase, respectively). Insulin pretreatment leads to a loss of insulin receptors in cultured human fibroblasts and preincubation with insulin led to a comparable dose-dependent decrease in subsequent insulin binding in both normal and diabetic fibroblasts. Scatchard analysis demonstrated that this decrease in binding was entirely due to a decrease in receptor number with no change in receptor affinity. These data demonstrate normal insulin binding, insulin internalization, and insulin-mediated receptor loss in fibroblasts from patients with with NIDDM, and these cells are several generations removed form the in vivo milieu...Continue Reading
Citations
Mar 1, 1996·Diabetologia·G SestiA Fusco
Sep 1, 1987·Journal of the Neurological Sciences·C Nakano, K Ohno
Sep 19, 1983·Life Sciences·H HidakaB V Howard
Aug 26, 1998·Metabolism: Clinical and Experimental·T P CiaraldiJ M Olefsky
Feb 1, 1991·American Journal of Respiratory Cell and Molecular Biology·L A Brown
Oct 1, 1993·Baillière's Clinical Endocrinology and Metabolism·W T Garvey, M J Birnbaum
Dec 1, 1989·Diabetes/metabolism Reviews·W T Garvey
Jul 1, 1989·Journal of Cellular Physiology·P A WhitsonN M Cintron
Jan 1, 1985·Journal of Cellular Biochemistry·R KadleR E Fellows
Sep 1, 1984·Diabetic Medicine : a Journal of the British Diabetic Association·R Taylor
Oct 1, 1988·Acta Paediatrica Japonica; Overseas Edition·T TakumiT Matsuo
Oct 1, 1988·Diabetic Medicine : a Journal of the British Diabetic Association·S S Reddy, C R Kahn
Oct 1, 1987·Journal of the American College of Nutrition·J Hallfrisch
Dec 7, 2017·Journal of Nutritional Science·Andressa R AmaralCarlos E Ambrósio
Dec 1, 1992·American Journal of Medical Genetics·E SeemanováM Dreyer
Dec 27, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Elena V GalkinaKlaus Ley
Nov 1, 1983·The American Journal of Physiology·R H Whitson, S A Kaplan
Nov 1, 1984·The American Journal of Physiology·K SugaharaR J Mason
Feb 21, 1997·Cell·J C BrüningC R Kahn
Jan 17, 1983·The American Journal of Medicine·O G KoltermanJ M Olefsky
Aug 15, 1988·Analytical Biochemistry·C A StuartA Green
Apr 30, 1985·Biochemical and Biophysical Research Communications·P Garcia-Webb, A M Bonser
Apr 16, 1982·Science·R DePirroR Dellatonio