From the Guidelines
Growth hormone has significant effects on intermediary metabolism pathways, primarily promoting anabolic processes while exerting anti-insulin or diabetogenic effects, as evidenced by its role in decreasing insulin sensitivity during puberty 1.
Effects on Carbohydrate Metabolism
- Growth hormone decreases glucose uptake in peripheral tissues by reducing insulin sensitivity, as seen in hyperinsulinemic-euglycemic clamp studies demonstrating 30% lower insulin-mediated glucose disposal in adolescents compared to prepubertal children and young adults 1.
- GH increases hepatic glucose production through glycogenolysis and gluconeogenesis, maintaining blood glucose levels during fasting.
Effects on Lipid Metabolism
- Growth hormone enhances lipolysis in adipose tissue, increasing free fatty acid release and oxidation, which provides energy and spares glucose utilization.
Clinical Implications
- The effects of growth hormone on intermediary metabolism pathways are crucial in understanding the development of type 2 diabetes in children and adolescents, particularly during puberty when insulin resistance is increased 1.
- Close monitoring of glucose metabolism is advised when initiating GH therapy in patients with chronic kidney disease due to an increased risk of impaired glucose tolerance 2. ### Key Findings
- Growth hormone secretion is most likely responsible for the insulin resistance during puberty, and both growth hormone secretion and insulin resistance decline with completion of puberty 1.
- The adverse effect of obesity on glucose metabolism is evident early in childhood, with obese children being hyperinsulinemic and having 40% lower insulin-stimulated glucose metabolism compared to nonobese children 1.
From the Research
Effects of Growth Hormone on Intermediary Metabolism Pathways
- Growth hormone (GH) has anabolic effects on glucose, lipid, and protein metabolism in human subjects 3
- GH stimulates the release and oxidation of free fatty acids (FFA), leading to decreased glucose and protein oxidation and preservation of lean body mass (LBM) and glycogen stores 3
- The most prominent metabolic effect of GH is a marked increase in lipolysis and FFA levels 3
- GH has a counterregulatory effect on insulin, inducing insulin resistance via mechanisms involving increased FFA flux and uptake 3, 4
- GH substitution in GH-deficient adults may worsen insulin resistance, but the GH-induced reduction in fat mass and increase in LBM may offset the insulin antagonistic actions of the hormone 5
Protein Metabolism
- GH has modest effects on protein metabolism in the basal state, including increased protein synthesis and decreased breakdown at the whole body level and in muscle 3
- During fasting and stress, the effects of GH on protein metabolism become more pronounced, with increased protein synthesis and decreased breakdown 3, 5
- Lack of GH during fasting increases protein loss and urea production rates by approximately 50%, with a similar increase in muscle protein breakdown 3
Lipid Metabolism
- GH mobilizes lipids by inhibiting lipoprotein lipase activity in adipose tissue and activating the hormone-sensitive lipase 5
- Chronic stimulation of lipolysis by GH results in an increased flux of free fatty acids (FFAs) into systemic circulation, contributing to the development of insulin resistance 6
- GH-induced lipolysis and impairment of insulin signaling are associated with deregulation of the FSP27-PPARγ axis, altering adipose tissue homeostasis and contributing to the development of insulin resistance and Type 2 diabetes 6