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Insulin does not stimulate protein synthesis acutely in prepubertal children with insulin-dependent diabetes mellitus
M G Vogiatzi1, K S Nair, P R Beckett
1Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
Insights
Insulin treatment in children with type 1 diabetes reduces protein breakdown but does not stimulate protein synthesis. This finding in children mirrors adult responses, indicating insulin
Area of Science:
- Pediatric Endocrinology
- Metabolic Research
- Diabetes Mellitus Type 1
Background:
- Insulin's role in protein metabolism differs between adult and young subjects.
- Adults with type 1 diabetes show decreased protein loss with insulin, mainly via reduced breakdown.
- Rodent studies suggest insulin may stimulate protein synthesis in young, growing individuals.
Purpose of the Study:
- To investigate if insulin stimulates protein synthesis in prepubertal children with insulin-dependent diabetes mellitus.
- To compare insulin's effect on protein metabolism in growing children versus adults and young rodents.
Main Methods:
- Studied five prepubertal children with type 1 diabetes (aged 8.6-11.25 years).
- Measured leucine kinetics using L-[1-13C]leucine infusion during insulin deprivation and administration.
- Analyzed serum insulin, beta-hydroxybutyrate, and free fatty acid concentrations.
Main Results:
- Insulin treatment significantly reduced protein breakdown (Leucine Ra) and leucine oxidation.
- Insulin administration normalized blood glucose levels and decreased ketone and fatty acid levels.
- Protein synthesis (nonoxidative leucine disposal) was not significantly affected by insulin treatment.
Conclusions:
- Acute insulin therapy in growing prepubertal children with type 1 diabetes reduces net protein loss.
- This reduction is primarily achieved by inhibiting protein breakdown, not by stimulating protein synthesis.
- The effect of insulin on protein metabolism in growing children is similar to that observed in adults.
Abstract:
Insulin treatment in adult type I diabetic patients decreases protein loss primarily by inhibiting protein breakdown without stimulating protein synthesis. In young growing rodents, insulin treatment has been reported to stimulate protein synthesis. We examined whether insulin stimulates protein synthesis in normally growing prepubertal children with insulin-dependent diabetes mellitus. Five prepubertal children with insulin-dependent diabetes mellitus (aged 8.6-11.25 yr) were studied in the postabsorptive state on two occasions: once during insulin deprivation (I-; blood glucose, 325 +/- 67.8 mg/dL; mean +/- SD) and once during insulin administration for 4 h (I+; blood glucose, 96 +/- 23.6 mg/dL). Leucine kinetics were measured using a 4-h primed continuous infusion of L-[1-13C]leucine. Serum insulin concentrations were lower (I- vs. I+, 0.6 +/- 0.3 vs. 7.5 +/- 4.3 microU/mL; mean +/- SD; P = 0.02), whereas serum beta-hydroxy-butyrate (I- vs. I+, 3.4 +/- 0.5 vs. 0.9 +/- 0.5 mg/dL; P < 0.001) and free fatty acid concentrations (I- vs. I+, 2.9 +/- 0.4 vs. 0.9 +/- 0.4 mEq/L; P < 0.001) were higher in the insulin-deprived state than during insulin administration. Leucine Ra, an index of protein breakdown (I- vs. I+, 200.5 +/- 23.4 vs. 167 +/- 17 mumol/kg.h; P = 0.008), and leucine oxidation (I- vs. I+, 56.5 +/- 20.7 vs. 29.6 +/- 9.3 mumol/kg.h; P = 0.03) were reduced by insulin treatment. Nonoxidative leucine disposal, an index of protein synthesis, was not affected by insulin treatment (I- vs. I+, 144 +/- 20.8 vs. 137.5 +/- 13.5 mumol/kg.h; P = 0.4). We conclude that the acute decline in net protein loss during insulin treatment in growing prepubertal children, like that in adults, is due primarily to an inhibition of protein breakdown without stimulation of protein synthesis.