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Insulin resistance of puberty: a defect restricted to peripheral glucose metabolism
S A Amiel1, S Caprio, R S Sherwin
1Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut.
Insights
Puberty causes insulin resistance primarily in peripheral glucose metabolism, not liver glucose production. This selective resistance may boost insulin
Area of Science:
- Pediatric Endocrinology
- Metabolic Research
- Human Physiology
Background:
- Insulin resistance is a hallmark of puberty, but its precise mechanisms remain unclear.
- Understanding these mechanisms is crucial for identifying potential interventions.
- Normal puberty involves significant physiological changes impacting metabolism.
Purpose of the Study:
- To investigate the specific mechanisms of insulin resistance development during normal human puberty.
- To differentiate the effects of puberty on peripheral glucose uptake versus hepatic glucose production.
- To explore the relationship between insulin sensitivity, insulin secretion, and substrate metabolism in prepubertal and pubertal children.
Main Methods:
- Sequential euglycemic and hyperglycemic insulin clamp studies were conducted in healthy prepubertal and pubertal children.
- Glucose turnover, hepatic glucose production, and peripheral glucose uptake were assessed.
- Plasma levels of branched-chain amino acids and free fatty acids (FFA) were measured.
Main Results:
- Pubertal children exhibited significantly lower peripheral glucose uptake in response to insulin compared to prepubertal children.
- Suppression of hepatic glucose production by insulin was not affected by pubertal status.
- Pubertal children demonstrated enhanced insulin responses and a greater reduction in amino acids during hyperglycemic clamp.
Conclusions:
- Insulin resistance during puberty is predominantly localized to peripheral tissues, affecting glucose metabolism.
- Compensatory hyperinsulinemia in puberty may enhance insulin's action on amino acid metabolism.
- This metabolic adaptation likely supports protein anabolism essential for rapid growth during puberty.
Abstract:
To examine mechanisms underlying the development of insulin resistance during normal puberty, sequential 8 and 40 mU/m2.min euglycemic insulin clamp and hyperglycemic clamp studies were performed in 14 healthy prepubertal and 19 pubertal children. Both groups had comparable rates of glucose turnover and plasma levels of branched chain amino acids and FFA at baseline. The low as well as the high insulin dose stimulated peripheral glucose uptake much more effectively in prepubertal children (P less than 0.05). In contrast, suppression of hepatic glucose production (60% at low dose in both groups, pNS) and lowering of substrates in response to insulin was not affected by puberty at either dose. During the hyperglycemic clamp pubertal children showed enhanced insulin responses and in turn a sharper fall in amino acids (P less than 0.05 vs. prepubertals). Our data suggest that insulin resistance during puberty is restricted to peripheral glucose metabolism. Selective insulin resistance leading to compensatory hyperinsulinemia may serve to amplify insulin's effect on amino acid metabolism, thereby facilitating protein anabolism during this period of rapid growth.