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

Journal Article · Fri May 01 04:00:00 EDT 1987 · J. Clin. Endocrinol. Metab.; (United States)

DOI:https://doi.org/10.1210/jcem-64-5-914· OSTI ID:6788466

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

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.

• Research Organization: Universita di Catania, Italy
• OSTI ID: 6788466
• Journal Information: J. Clin. Endocrinol. Metab.; (United States), Journal Name: J. Clin. Endocrinol. Metab.; (United States) Vol. 5; ISSN JCEMA
• Country of Publication: United States
• Language: English

Related Subjects

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