title: Endogenous chronic hyperinsulinemia does not increase the production rate of VLDL apolipoprotein B: proof from a kinetic study in patients with insulinoma.
abstract: OBJECTIVE
  It is currently suggested that chronic hyperinsulinemia is a causal factor for the increased production rate of very-low-density lipoproteins (VLDL) associated with metabolic syndrome. However, the involvement of hyperinsulinemia independently of the other abnormalities also observed in metabolic syndrome has never been proven in humans.
  
  
  METHODS
  We used patients with insulinoma showing hyperinsulinemia but no insulin resistance as a model and conducted an apolipoprotein B (apoB) kinetic study in seven patients with insulinoma, seven insulin-resistant (IR) obese patients, and 12 controls.
  
  
  RESULTS
  Insulinemia was higher in patients with insulinoma or IR than in controls both in the fasting state [2.4-fold (P = 0.039) and 3.1-fold (P = 0.003), respectively] and in the fed state [3.5-fold (P = 0.006) and 2.6-fold (P = 0.05), respectively]. Patients with insulinoma were not IR (steady state plasma glucose = 80 ± 46 mg/dl, a value lower than in IR subjects (231 ± 75, P = 0.0013). In the fed state, triglyceridemia and VLDL apoB pool size were higher in IR subjects compared with controls and patients with insulinoma [208 ± 56 vs. 89 ± 30 mg/dl (P < 0.0001) and 96 ± 42 mg/dl (P < 0.0001), respectively, for triglyceridemia and 3.56 ± 0.60 vs. 1.85 ± 0.88 mg/kg (P = 0.004) and 2.32 ± 1.79 (P = 0.052) mg/kg for VLDL apoB pool size]. The production rate of VLDL apoB in subjects with insulinoma was not significantly different from that in controls (14.56 ± 7.43 vs. 16.40 ± 7.70 mg/kg · d) but was higher in IR subjects compared with these two groups [25.66 ± 12.84 mg/kg · d (P = 0.046 and 0.035, respectively)].
  
  
  CONCLUSIONS
  Chronic endogenous hyperinsulinemia is not directly responsible for any increase in the production rate of VLDL apoB in humans.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 866, Université de Bourgogne, Faculté de Médecine, Dijon F-21000 France. laurence.duvillard@chu-dijon.fr
authors.forename: Laurence
authors.initials: L
authors.lastname: Duvillard
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Florentin
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pont
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Petit
authors.forename: Sabine
authors.initials: S
authors.lastname: Baillot-Rudoni
authors.forename: Alfred
authors.initials: A
authors.lastname: Penfornis
authors.forename: Bruno
authors.initials: B
authors.lastname: Vergès
mesh_terms: D001055:Apolipoproteins B / Q000096:biosynthesis*; D006801:Humans; D006946:Hyperinsulinism / Q000209:etiology / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D007340:Insulinoma / Q000150:complications / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000096:biosynthesis*; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000150:complications / Q000378:metabolism*
chemical_list: D001055:Apolipoproteins B; D008079:Lipoproteins, VLDL