Intracellular hyperinsulinism: a metabolic characteristic of obesity with and without type 2 diabetes - Intracellular insulin in obesity and Type 2 diabetes

There is evidence that intracellular insulin may carry out some insulin med iated actions, including glucose transport. As intracellular insulin has ne ver been quantitatively assessed in human cells, we evaluated its concentra tions in monocytes from normal subjects (n = 7) and obese patients without (n = 9) and with Type 2 diabetes mellitus (n = 10). After the incubation of cells with labeled insulin for 60 min at 37 degrees C, intracellular intac t insulin concentrations were measured by HPLC and expressed as pmol.10(-6) . Insulin concentrations were higher (ANOVA P < 0.01) within cells from obe se (115.4 +/- 26.4 pmol . 10(-6)/2 . 10(5) cells) and obese diabetic patien ts (93.2 +/- 36.3 pmol.10(-6)/ 2 . 10(5) cells) compared with normal cells (28.5 +/- 13.1 pmol . 10(-6)/2 . 10(5) cells). Moreover, after insulin was removed from the incubation medium the decrease of intracellular insulin wa s significantly lower (P < 0.01) in cells from both obese and obese diabeti c patients than in normal subjects. Intracellular undissociated insulin-ins ulin receptor complexes on average, increased 2-fold (P < 0.01) in cells fr om insulin resistant patients compared with normal cells. Finally, in downr egulated cells from obese and obese diabetic patients, the recycling of the internalized insulin receptor was completely disrupted. In conclusion, mon ocytes from obese patients with and without Type 2 diabetes mellitus, prese nt increased intracellular insulin concentrations and these conditions are associated with a significant impairment of insulin receptor processing. In creased intracellular insulin concentration in cells from these patients ma y be necessary in order to overcome insulin resistance. (C) 1999 Elsevier S cience Ireland Ltd. All rights reserved.