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 mediated actions, including glucose transport. As intracellular insulin has never been quantitatively assessed in human cells, we evaluated its concentrations 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 intact insulin concentrations were measured by HPLC and expressed as pmol.10(-6). Insulin concentrations were higher (ANOVA P < 0.01) within cells from obese (115.4 +/- 26.4 pmol . 10(-6)/2 . 10(5) cells) and obese diabetic patients (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 was significantly lower (P < 0.01) in cells from both obese and obese diabetic patients than in normal subjects. Intracellular undissociated insulin-insulin receptor complexes on average, increased 2-fold (P < 0.01) in cells from insulin resistant patients compared with normal cells. Finally, in downregulated cells from obese and obese diabetic patients, the recycling of the internalized insulin receptor was completely disrupted. In conclusion, monocytes from obese patients with and without Type 2 diabetes mellitus, present increased intracellular insulin concentrations and these conditions are associated with a significant impairment of insulin receptor processing. Increased intracellular insulin concentration in cells from these patients may be necessary in order to overcome insulin resistance. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.