Intracellular insulin processing is altered in monocytes from patients with type II diabetes mellitus

Trischitta, V; Benzi, L; Brunetti, A; Cecchetti, P; Marchetti, P; Vigneri, R; Navalesi, R

doi:10.1210/jcem-64-5-914

Title: Intracellular insulin processing is altered in monocytes from patients with type II diabetes mellitus

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Abstract

We studied total cell-associated A14-(/sup 125/I)insulin radioactivity (including surface-bound and internalized radioactivity), insulin internalization, and its intracellular degradation at 37 C in monocytes from nonobese type II untreated diabetic patients (n = 9) and normal subjects (n = 7). Total cell-associated radioactivity was decreased in diabetic patients (2.65 +/- 1.21% (+/- SD) vs. 4.47 +/- 1.04% of total radioactivity. Insulin internalization was also reduced in diabetic patients (34.0 +/- 6.8% vs. 59.0 +/- 11.3% of cell-associated radioactivity. Using high performance liquid chromatography six intracellular forms of radioactivity derived from A14-(/sup 125/I) insulin were identified; 10-20% of intracellular radioactivity had approximately 300,000 mol wt and was identified as radioactivity bound to the insulin receptor, and the remaining intracellular radioactivity included intact A14-(/sup 125/I)insulin, (/sup 125/I)iodide, or (/sup 125/I)tyrosine, and three intermediate compounds. A progressive reduction of intact insulin and a corresponding increase in iodine were found when the incubation time was prolonged. Intracellular insulin degradation was reduced in monocytes from diabetic patients; intracellular intact insulin was 65.6 +/- 18.1% vs. 37.4 +/- 18.0% of intracellular radioactivity after 2 min and 23.6 +/- 22.3% vs. 3.9 +/- 2.3% after 60 min in diabetic patients vs. normal subjects, respectively. In conclusion, 1) humanmore »« less

Authors:: Trischitta, V; Benzi, L; Brunetti, A; Cecchetti, P; Marchetti, P; Vigneri, R; Navalesi, R

Publication Date:: Fri May 01 00:00:00 EDT 1987

Research Org.:: Universita di Catania, Italy

OSTI Identifier:: 6788466

Resource Type:: Journal Article

Journal Name:: J. Clin. Endocrinol. Metab.; (United States)

Additional Journal Information:: Journal Volume: 5

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; DIABETES MELLITUS; ETIOLOGY; INSULIN; BIOCHEMICAL REACTION KINETICS; IODIDES; IODINE 125; KINETICS; MONOCYTES; TRACER TECHNIQUES; TYROSINE; AMINO ACIDS; BETA DECAY RADIOISOTOPES; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY FLUIDS; CARBOXYLIC ACIDS; DAYS LIVING RADIOISOTOPES; DISEASES; ELECTRON CAPTURE RADIOISOTOPES; ENDOCRINE DISEASES; HALIDES; HALOGEN COMPOUNDS; HORMONES; HYDROXY ACIDS; INTERMEDIATE MASS NUCLEI; IODINE COMPOUNDS; IODINE ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; LEUKOCYTES; MATERIALS; METABOLIC DISEASES; NUCLEI; ODD-EVEN NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; PEPTIDE HORMONES; RADIOISOTOPES; REACTION KINETICS; 550901* - Pathology- Tracer Techniques

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                    Trischitta, V, Benzi, L, Brunetti, A, Cecchetti, P, Marchetti, P, Vigneri, R, and Navalesi, R. Intracellular insulin processing is altered in monocytes from patients with type II diabetes mellitus.  United States: N. p., 1987. 
        Web.  doi:10.1210/jcem-64-5-914.

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                    Trischitta, V, Benzi, L, Brunetti, A, Cecchetti, P, Marchetti, P, Vigneri, R, & Navalesi, R. Intracellular insulin processing is altered in monocytes from patients with type II diabetes mellitus.  United States.  https://doi.org/10.1210/jcem-64-5-914

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                    Trischitta, V, Benzi, L, Brunetti, A, Cecchetti, P, Marchetti, P, Vigneri, R, and Navalesi, R. 1987.  
        "Intracellular insulin processing is altered in monocytes from patients with type II diabetes mellitus".  United States.  https://doi.org/10.1210/jcem-64-5-914.

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@article{osti_6788466,

  title        = {Intracellular insulin processing is altered in monocytes from patients with type II diabetes mellitus},

  author       = {Trischitta, V and Benzi, L and Brunetti, A and Cecchetti, P and Marchetti, P and Vigneri, R and Navalesi, R},

  abstractNote = {We studied total cell-associated A14-(/sup 125/I)insulin radioactivity (including surface-bound and internalized radioactivity), insulin internalization, and its intracellular degradation at 37 C in monocytes from nonobese type II untreated diabetic patients (n = 9) and normal subjects (n = 7). Total cell-associated radioactivity was decreased in diabetic patients (2.65 +/- 1.21% (+/- SD) vs. 4.47 +/- 1.04% of total radioactivity. Insulin internalization was also reduced in diabetic patients (34.0 +/- 6.8% vs. 59.0 +/- 11.3% of cell-associated radioactivity. Using high performance liquid chromatography six intracellular forms of radioactivity derived from A14-(/sup 125/I) insulin were identified; 10-20% of intracellular radioactivity had approximately 300,000 mol wt and was identified as radioactivity bound to the insulin receptor, and the remaining intracellular radioactivity included intact A14-(/sup 125/I)insulin, (/sup 125/I)iodide, or (/sup 125/I)tyrosine, and three intermediate compounds. A progressive reduction of intact insulin and a corresponding increase in iodine were found when the incubation time was prolonged. Intracellular insulin degradation was reduced in monocytes from diabetic patients; intracellular intact insulin was 65.6 +/- 18.1% vs. 37.4 +/- 18.0% of intracellular radioactivity after 2 min and 23.6 +/- 22.3% vs. 3.9 +/- 2.3% after 60 min in diabetic patients vs. normal subjects, respectively. In conclusion, 1) human monocytes internalize and degrade insulin in the intracellular compartment in a stepwise time-dependent manner; and 2) in monocytes from type II diabetic patients total cell-associated radioactivity, insulin internalization, and insulin degradation are significantly reduced. These defects may be related to the cellular insulin resistance present in these patients.},

  doi          = {10.1210/jcem-64-5-914},

  url          = {https://www.osti.gov/biblio/6788466},
  journal      = {J. Clin. Endocrinol. Metab.; (United States)},
number       = ,

  volume       = 5,

  place        = {United States},

  year         = {Fri May 01 00:00:00 EDT 1987},

  month        = {Fri May 01 00:00:00 EDT 1987}

}

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