title: The effect of experimentally induced insulin resistance on the leptin response to hyperinsulinaemia.
abstract: OBJECTIVE
  Insulin is thought to be an important regulator of leptin secretion. However, increasing evidence suggests that insulin-mediated glucose uptake rather than insulin per se regulates circulating leptin concentration. Here, we hypothesised that a reduction of insulin sensitivity, ie insulin resistance, will diminish the stimulatory effect of insulin on leptin secretion as a consequence of decreased insulin-mediated glucose uptake.
  
  
  METHODS
  Changes in serum leptin concentration during 30 hyperinsulinaemic-hypoglycaemic clamps were studied after induction of different levels of insulin resistance in normal-weight men. In 15 subjects insulin sensitivity was reduced by exposing them to a 2.5 h antecedent hypoglycaemia (3.1 mmol/l) induced by a high rate of insulin infusion (15.0 mU/min/kg) on the day before the proper experiment ('ante-hypo' condition). In the other 15 subjects no antecedent hypoglycaemia was induced ('control' condition). The proper experiment on both conditions was a 6 h stepwise hypoglycaemic clamp induced by a constant rate of insulin infusion (1.5 mU/min/kg).
  
  
  METHODS
  Experiments were carried out in 30 lean healthy subjects (age, mean +/- s.e.m., 26 +/- 1 y; body mass index, 23.1 +/- 0.6 kg/m2).
  
  
  RESULTS
  As expected, glucose demand during the clamp was lower in the ante-hypo condition than in the control condition (gram of glucose infused per kilogram body weight, 1.52 +/- 0.16 vs 2.01 +/- 0.17 g/kg; P < 0.05). During the clamp, leptin levels increased by 25.4 +/- 4.3% in the control condition (P < 0.05), but not in the ante-hypo condition (+4.8 +/- 4.5%; P > 0.25). Thus, serum leptin response to the clamp significantly differed between the two conditions (P < 0.01). Across both conditions, the increase of leptin levels during the clamp was correlated with the amount of glucose infused (r = 0.37; P < 0.05).
  
  
  CONCLUSIONS
  Considering that insulin concentrations were identical during both clamp conditions, the data indicate that experimentally-induced insulin resistance diminishes the stimulatory effect of insulin on leptin secretion.
authors.affiliation: Department of Internal Medicine I, University of Luebeck, Germany. fruelwald@kfg.mu-luebeck.de
authors.forename: B
authors.initials: B
authors.lastname: Fruehwald-Schultes
authors.forename: K M
authors.initials: KM
authors.lastname: Oltmanns
authors.forename: W
authors.initials: W
authors.lastname: Kern
authors.forename: J
authors.initials: J
authors.lastname: Born
authors.forename: H L
authors.initials: HL
authors.lastname: Fehm
authors.forename: A
authors.initials: A
authors.lastname: Peters
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D015309:Glucose Clamp Technique; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006946:Hyperinsulinism / Q000097:blood*; D007003:Hypoglycemia; D007333:Insulin Resistance; D007700:Kinetics; D020738:Leptin / Q000097:blood*; D008297:Male
chemical_list: D001786:Blood Glucose; D020738:Leptin; D006854:Hydrocortisone