The effect of experimentally induced insulin resistance on the leptin response to hyperinsulinaemia.
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.
Fruehwald-Schultes
B
B
Department of Internal Medicine I, University of Luebeck, Germany. fruelwald@kfg.mu-luebeck.de
Oltmanns
K M
KM
Kern
W
W
Born
J
J
Fehm
H L
HL
Peters
A
A
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
D001786:Blood Glucose; D020738:Leptin; D006854:Hydrocortisone