Correlations between fatty acid and glucose metabolism. Potential explanation of insulin resistance of puberty.
In vivo resistance to the action of insulin on glucose uptake has been documented during puberty. To test the hypothesis that the glucose-fatty acid cycle, as proposed by Randle et al. (Randle PJ, Garland PB, Hales CN, Newsholme EA: The glucose fatty-acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785-789, 1963), may be responsible for this phenomenon, we studied nine prepubertal (Tanner I), nine pubertal (Tanner II-IV), and five young adult healthy subjects. The rate of lipolysis was measured with [d-5]glycerol tracer during basal state and during a stepwise hyperinsulinemic (10 and 40 mU.m-2.min-1)-euglycemic clamp. The rates of insulin-stimulated glucose disposal (Rd) were measured during the clamp, whereas glucose and fat oxidation were measured by using indirect respiratory calorimetry. Basal glycerol rate of appearance (Ra; lipolysis) and fat oxidation were similar between prepubertal and pubertal subjects but higher than adults when the data were expressed per kilogram body weight or per kilogram fat-free mass (FFM; glycerol Ra: 2.5 +/- 0.2, 2.6 +/- 0.2 vs. 1.6 +/- 0.2 mumol.min-1.kg FFM-1, P < 0.05; fat oxidation: 4.4 +/- 0.6, 4.8 +/- 0.3 vs. 3.2 +/- 0.6 mumol.min-1.kg FFM-1, P < 0.05). However, when expressed for total body, glycerol Ra and fat oxidation were higher in pubertal versus prepubertal and adult subjects. Insulin-like growth factor I (IGF-I) levels correlated with total-body lipolysis (r = 0.52, P = 0.006) and with total lipid oxidation (r = 0.44, P = 0.016) at baseline.(ABSTRACT TRUNCATED AT 250 WORDS)
Division of Pediatric Endocrinology, Metabolism, and Diabetes Mellitus, Children's Hospital, University of Pittsburgh, Pennsylvania 15213.
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Arslanian
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Kalhan
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000704:Analysis of Variance; D001481:Basal Metabolism; D001786:Blood Glucose / Q000378:metabolism*; D001823:Body Composition; D001834:Body Water / Q000502:physiology; D002648:Child; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008066:Lipolysis; D008297:Male; D010103:Oxygen Isotopes; D011627:Puberty / Q000378:metabolism*; D012044:Regression Analysis
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010103:Oxygen Isotopes; D005947:Glucose; D005990:Glycerol