Effect of insulin on glycerol production in obese adolescents.
Impaired stimulation of glucose metabolism and reduced suppression of lipolytic activity have both been suggested as important defects related to the insulin resistance of adolescent obesity. To further explore the relationship between these abnormalities, we studied seven obese [body mass index (BMI) 35 +/- 2 kg/m2] and seven lean (BMI 21 +/- 1 kg/m2) adolescents aged 13-15 yr and compared them with nine lean adults (aged 21-27 yr, BMI 23 +/- 1 kg/m2) during a two-step euglycemic-hyperinsulinemic clamp in combination with 1) a constant [2H5]glycerol (1.2 mg.m-2.min-1) infusion to quantify glycerol turnover and 2) indirect calorimetry to estimate glucose and net lipid oxidation rates. In absolute terms, basal glycerol turnover was increased and suppression by insulin was impaired in obese adolescents compared with both groups of lean subjects (P < 0.01). However, when the rates of glycerol turnover were adjusted for differences in body fat mass, the rates were similar in all three groups. Basal plasma free fatty acid (FFA) concentrations were significantly elevated, and the suppression by physiological increments in plasma insulin was impaired in obese adolescents compared with lean adults (P < 0.05). In parallel with the high circulating FFA levels, net lipid oxidation in the basal state and during the clamp was also elevated in the obese group compared with lean adults. Net lipid oxidation was inversely correlated with glucose oxidation (r = -0.50, P < 0.01). In conclusion, these data suggest that lipolysis is increased in obese adolescents (vs. lean adolescents and adults) as a consequence of an enlarged adipose mass rather than altered sensitivity of adipocytes to the suppressing action of insulin.
Robinson
C
C
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Tamborlane
W V
WV
Maggs
D G
DG
Enoksson
S
S
Sherwin
R S
RS
Silver
D
D
Shulman
G I
GI
Caprio
S
S
D000293:Adolescent; D000328:Adult; D002096:C-Peptide / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D009994:Osmolar Concentration
D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005947:Glucose; D005990:Glycerol