Diabetes, Vol 38, Issue 12 1579-1584, Copyright © 1989 by American Diabetes Association

ARTICLES

Defects in insulin-receptor internalization and processing in monocytes of obese subjects and obese NIDDM patients

V Trischitta, A Brunetti, A Chiavetta, L Benzi, V Papa and R Vigneri
Department of Endocrinology, University of Catania, Italy.

We investigated intracellular processing of the insulin-receptor complex in monocytes from 12 healthy control subjects, 11 obese nondiabetic subjects, and 13 obese patients with non-insulin-dependent diabetes mellitus (NIDDM) by measuring receptor internalization, recovery of cell-surface insulin binding after receptor internalization, and the release of intracellular intact insulin (insulin retroendocytosis). When monocytes from the three groups of subjects were exposed to 100 nM unlabeled insulin for 30 min at 37 degrees C, the subsequent cell-surface 125I-labeled insulin binding was reduced, but the total number of insulin receptors, measured by radioimmunoassay, was not changed. These findings indicate a redistribution of insulin receptors from the surface to the cell interior. Insulin-receptor internalization was significantly lower in monocytes of obese NIDDM patients (mean +/- SE 17.8 +/- 4.7%) than in obese subjects and healthy control subjects (33.5 +/- 4.5%, P less than .05, and 34.4 +/- 3.7%, P less than .02, respectively). Moreover, in downregulated cells, a complete recovery of the initial insulin binding was observed in control subjects but not in obese NIDDM patients or obese nondiabetic subjects. The release of internalized insulin was also reduced in obese NIDDM patients and obese subjects (t 1/2 = 49.0 +/- 2.4 min, P less than .02; 47.4 +/- 5.7 min, P less than .05; and 32.9 +/- 3.8 in NIDDM patients, obese subjects, and control subjects, respectively). In the radioactivity released from monocytes of obese subjects and obese NIDDM patients, the percentage of intact insulin was higher (P less than .05) than in control subjects, suggesting reduced intracellular insulin degradation in obese subjects and obese NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. N. Rudovich, H. J. Rochlitz, and A. F.H. Pfeiffer Reduced Hepatic Insulin Extraction in Response to Gastric Inhibitory Polypeptide Compensates for Reduced Insulin Secretion in Normal-Weight and Normal Glucose Tolerant First-Degree Relatives of Type 2 Diabetic Patients Diabetes, September 1, 2004; 53(9): 2359 - 2365. [Abstract] [Full Text] [PDF]

				M. L. Hribal, R. D'Alfonso, B. Giovannone, D. Lauro, Y. Y. Liu, P. Borboni, M. Federici, R. Lauro, and G. Sesti The Sulfonylurea Glimepiride Regulates Intracellular Routing of the Insulin-Receptor Complexes through Their Interaction with Specific Protein Kinase C Isoforms Mol. Pharmacol., February 1, 2001; 59(2): 322 - 330. [Abstract] [Full Text]

				H. Fakhrai-Rad, A. Nikoshkov, A. Kamel, M. Fernstrom, J. R. Zierath, S. Norgren, H. Luthman, and J. Galli Insulin-degrading enzyme identified as a candidate diabetes susceptibility gene in GK rats Hum. Mol. Genet., September 1, 2000; 9(14): 2149 - 2158. [Abstract] [Full Text] [PDF]

				W. C. Duckworth, R. G. Bennett, and F. G. Hamel Insulin Degradation: Progress and Potential Endocr. Rev., October 1, 1998; 19(5): 608 - 624. [Abstract] [Full Text]

				K. Yamada, J.-L. Carpentier, B. Cheatham, E. Goncalves, S. E. Shoelson, and C. R. Kahn Role of the Transmembrane Domain and Flanking Amino Acids in Internalization and Down-regulation of the Insulin Receptor J. Biol. Chem., February 17, 1995; 270(7): 3115 - 3122. [Abstract] [Full Text] [PDF]