GH, (HGH, somatotropin) is a protein synthesized and stored in somatotroph cells in the anterior pituitary gland. The growth hormone mainly fuels childhood growth, but in addition to this, it also maintains cell reproduction and proliferation throughout adult life. On stimulation from the hypothalamus through GHRH, GH is released by the anterior pituitary in a pulsatile manner.
HGH, on being released from the anterior pituitary, stimulates the liver production of IGF-1, which in turn, inhibits GH release with negative feedback. Along with IGF1, GHRH, and SS, Insulin also plays a role in the regulation of GH. HGH secretion is also stimulated by the release of ghrelin, the hunger hormone, and inhibited by SS, another hormone released from the hypothalamus.
GH, once in circulation, has many functions such as lipolysis, glucose metabolism, and protein synthesis. Hence, this implies that the factors which affect these processes can also affect GH levels in serum, especially insulin.
On reaching the circulation, HGH then acts on GHR and activates signaling pathways. These processes are divided into two, Pre-GHR processes which include secretion of GH and maintenance of GH levels in the blood, and Post-GHR processes which involve recognition by GHR and subsequent activation of signaling pathways. These pathways are GHR/JAK2/STATs, GHR/ JAK2/SHC/MAPK, and GH/IRS/PI3K/Akt pathways. Most GH disorders are due to a mutation of STAT 5b Receptor, indicating its importance in the functioning of HGH. However, these receptors also are activated by other hormones, explaining the correlation between GH and these hormones.
Researchers Examine GH’s role In Diabetes
Research on the pathophysiology of diabetes has shown a major relation between GH and Insulin, both of which have opposite functions. Insulin and GH maintain a balance in a healthy individual but in patients with DM, low levels of insulin reduce the sensitivity of GHRHR to GH and increase the level of SS, hence destroying the balance between GH, insulin, and glucose metabolism.
Understanding this further, in relation to both T1DM and T2DM, might help researchers in developing new methods of treatment for these disorders. Along with diabetes, the balance between GH and insulin also plays an important role in the development and progression of obesity through their effect on lipid metabolism. Furthermore, obesity is one of the key factors leading to T2DM. However, the regulation of GH by insulin is different in obese and diabetic patients as such that inhibition of GH in obese people is due to IR whereas SS, and desensitization of GHRHR are responsible for low levels of GH in diabetic patients.
Insulin doesn’t only affect HGH levels in circulation but can also affect HGH function by interfering in the Post-GHR processes. Both hormones share the three pathways mentioned above, and this helps with GH and Insulin interaction. However, they use these pathways for different purposes. Insulin affects GH signaling in time and dose-dependent methods, depending on multiple factors like IRS, SOCS, GHR sensitivity, and the signaling pathways they share.
In conclusion, Insulin is required for the maintenance of the level of HGH within the body. The effect of insulin on GH levels is determined by its secretion and sensitivity of GHR, along with obesity levels, and to some extent, IGF-1. Insulin, however, doesn’t just work on pre-GHR processes but also on post-GHR processes by activating the GH-induced MAPK pathway and phosphorylating STAT5. It has a negative effect on the JAK2 and GHR/STAT5 pathways. However, these pathways’ effects need to be studied further in large-scale studies that represent the general population.