Role of HGH on Glucose Homeostasis in Humans

Growth hormone (GH, HGH, or Somatotropin) is involved in a multitude of roles within the body from the growth of bones, muscles, and vital organs to the regulation of hormonal pathways. GH levels have shown to subsequently affect the expression of insulin-like growth factor-1. Previous research has focused on the relationship between levels of GH and glucose metabolism solely through in vivo studies in animal models. As such, researchers have now diverted their attention towards investigating the impact of HGH on metabolic processes related to glucose and insulin in the human body.

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Maintaining glucose homeostasis is essential in preventing diseases resulting from either hypoglycemia or hyperglycemia, Insulin and glucagon are the two most important regulators of glucose levels in the blood. To this end, growth hormone has been shown to mirror the effect of glucagon by counteracting insulin and decreasing glucose levels in the body.

Research has shown that individuals with excess production of GH have an increased chance of developing diabetes. The effect of GH on glucose homeostasis is via two pathways, direct and indirect. Researchers have recently conducted a study in order to evaluate and understand the major pathways through which GH can affect glucose production.

Direct effects on glucose homeostasis

Growth hormone has been shown to act like glucagon by stimulating processes such as gluconeogenesis. Studies have shown that individuals with high growth hormone levels have an increased expression of genes that regulate gluconeogenesis.

Additionally, research has illustrated the effect of GH on glucose transporters. GH suppresses GLUT transporters, thereby preventing the uptake of glucose within cells. HGH does this by its action on phosphoinositide 3-kinase (PI3K) signaling pathway that is responsible for GLUT translocation via increased expression of p85 subunit that in turn downregulates PI3K and prevents GLUT translocation.

In adipose tissue, GH has been shown to increase fatty acid synthesis which further exacerbates insulin resistance. The mechanism for this is thought to be by GH’s inhibition of insulin receptor substrate-1 (IRS-1) and downregulation of the PI3K pathway. In contrast, HGH in muscle cells stimulates the production of triglycerides and uptake of fatty acids. A novel mechanism involving reduced insulin sensitivity has been suggested regarding the direct effect of GH on glucose mechanism albeit not confirmed in humans.

Indirect effects on glucose homeostasis

GH indirectly acts on blood glucose levels through regulation of IGF-1, which mimics insulin’s effect in the body. Animal studies conducted in vivo have shown that IGF-1 can promote glucose uptake from the blood in an effort to lower glucose levels. Research conducted by Di Cola and colleagues has demonstrated that IGF-1 mimics insulin by stimulating glycolysis in mice deficient of insulin receptors compared to normal mice.

GH deficiency and glycemic control in adults

Growth hormone deficiency (GHD) occurs when there are insufficient quantities of GH that cannot meet the body’s remodeling demands. Low levels in GH correlate with low levels of IGF-1 and contribute to the disruption of important metabolic pathways within the body. Multiple studies have attempted to administer GH in these patients in an effort to treat GHD. Although few studies have reported positive effects related to glycemic control in GHD-individuals who are treated with GH, the findings are yet to be confirmed via larger-scale studies.

The changes observed in glucose levels in GHD patients treated with GHD is a complex and multifactorial issue. For example, the dosage and duration of the treatment have been shown to play an important role in the development of cells that are not responsive to insulin. Treatments longer than 1 year that require high doses of HGH have been linked to reduced glucose uptake. Moreover, a high dosage of GH (≥0.01 mg/kg/day) has shown to reduce body fat and improve overall physique. Several studies have examined the effect of a low dose of GH (<0.01 mg/kg/day) on glucose levels and HbA1c. The results were comparable and concluded that low dose treatment of GH over a long period of time does not affect fasting glucose or HbA1c.

Some studies have also investigated the increased prevalence of diabetes in patients after low-dose GH therapy. However, to this date, studies have not found a link between the development of diabetes in GHD-individuals following low-dose therapy.

GH deficiency and glycemic control in children

Although there is a growing body of evidence of the positive changes in glucose levels in GHD-individuals after GH treatment, this has not been the case in children. Minimal studies have been conducted that observe the phenomena of decreased insulin sensitivity in children.

Similar to adults, GHD children may have a higher likelihood of developing diabetes after GH therapy. An array of studies has examined the prevalence of type I and type II diabetes between the GHD children and the general population. Studies focused on type I diabetes revealed no difference in GHD children compared to the population. On the other hand, studies that investigated type II diabetes revealed that type II diabetes was more common in children undergoing GH therapy compared to healthy controls.

Growth hormone has been shown to counteract insulin by stimulating glucose-producing processes. IGF-1 was shown to function similarly to insulin by decreasing glucose levels. GH treatment in GHD-individuals has shown to increase the prevalence of type II diabetes, especially in the pediatric population. Therefore, it is important to stay vigilant and examine the effects of glucose metabolism when treating children with GHD as there continues to be a dire need for clinical trials investigating the effects of HGH therapy on glucose levels in GHD patients.

References

Effects of growth hormone on glucose metabolism and insulin resistance in human

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