Defective insulin action on protein and glucose metabolism during chronic hyperinsulinemia in subjects with benign insulinoma

A. Battezzati, I. Terruzzi, G. Perseghin, E. Bianchi, V. Di Carlo, G. Pozza, L. Luzi

Research output: Contribution to journalArticlepeer-review


The ability of chronic endogenous hyperinsulinemia to induce a resistance to insulin action on protein and glucose metabolism was studied in 10 subjects affected by a benign (functioning) insulinoma and 18 healthy subjects by means of infusions of [1-14C]leucine and [3-3H] glucose. The insulinoma subjects were divided into two groups with moderate (139 ± 12 pmol/l) (n = 5) and marked (438 ± 42 pmol/l) (n = 5) hyperinsulinemia and were studied during a euglycemic dextrose infusion. Control subjects were studied postabsorptively and during a low-dose (0.3 mU · kg-1 · min-1) (n = 3) and a high-dose (1 mU · kg-1 · min-1) (n = 15) euglycemic insulin clamp to match peripheral insulin concentrations with those of insulinoma subjects. In insulinoma subjects there was no correlation among plasma insulin concentration and leucine concentration (r = 0.05), endogenous leucine flux (r = 0.44), hepatic glucose production (r = 0.47), and glucose uptake (r = 0.05). Insulinoma subjects with marked hyperinsulinemia demonstrated a defective suppression of leucine concentrations (100 ± 11 vs. 65 ± 5 μmol/l, P <0.01), endogenous leucine flux (50.1 ± 6.3 vs. 27.1 ± 0.9 μmol · m-2 · min-1, P <0.01), and hepatic glucose production (5.4 ± 2.0 vs. 0.6 ± 0.6 μmol · kg-1. min-1, P <0.05), and a defective stimulation of glucose uptake (13.5 ± 1.6 vs. 41.1 ± 2.8 μmol · kg-1 · min-1, P <0.001) with respect to normal subjects at a comparable degree of hyperinsulinemia. Our results demonstrate that chronic endogenous hyperinsulinemia causes a defect in insulin action that is generalized to both protein metabolism and hepatic and peripheral glucose metabolism.

Original languageEnglish
Pages (from-to)837-844
Number of pages8
Issue number7
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine


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