MY DIARY GAME| BY JOYVIC| THE ROLE OF INSULIN IN GLYCOGEN| DECEMBER 6,2021
Hello dearest, I hope our morning is goin on cool?. I would like to continue on my lecture on HORMONES. The aim of the content is to give a knowledge of it. I hope you will be blessed. I will continue on the role of insulin in glycogen metabolism.
Role of insulin in glycogen metabolism Similar to glucagon, insulin also elicits response at target sites by activating a cascade of enzymatic activities through mutual activation of protein kinases .
However, the cascade of enzymatic reactions elicited by insulin, ultimately results in changes in gene transcription within the nucleus through phosphorylation reactions which promote uptake of glucose and its conversion to glycogen
Insulin also stimulates the synthesis of glycogen in muscle and liver cells by promoting a decrease in the phosphorylation of glycogen synthase hence, increasing its activity
Insulin therefore enhances synthesis of glycogen, while inhibiting its breakdown .
Apart from G Protein – Coupled receptors, we also have the Protein Kinase – Associated receptors, an example of which is the Receptor Tyrosine Kinase (RTK), to which insulin binds, to exert its hormonal effects
There are well over 50 receptor tyrosine kinases, belonging to at least 13 different receptor families, some of which include the insulin receptor, nerve growth factor (NGF), epidermal growth factor (EGF), platelete derived growth factor (PDGF) and fibroblast growth factor (FGF)
All Receptor Tyrosine Kinases are usually single peptides with: A large glycosylated extracellular ligand binding domain A single trans-membrane region A cytosolic portion having a conserved catalytic protein tyrosine kinase domain; a juxta-membrane region and a C – terminal tail.
The trans-membrane portion of RTKs anchors the receptor in the plane of the plasma membrane, thereby connecting the extracellular environment with the internal milieu
The juxta-membrane sequence of the receptor separates the trans-membrane domain from the cytoplasmic domains
It is also involved in the modulation of the activities of the receptor, a process known as receptor trans-modulation
In some cases, the juxta-membrane region also binds to specific substrates in a ligand-dependent manner hence, playing a role in cell signaling
The tyrosine kinase domain is the most conserved region of RTKs and must remain intact for receptor signaling to occur
The C – terminal of RTKs is the least conserved sequence and is believed to be involved in the regulation of kinase activity
It contains several tyrosine residues, which are phosphorylated during receptor activation
A specific feature of the insulin receptor is the presence of four subunits – two α and two β subunits, held together by di-sulphide bonds
The two α subunits lie outside the cell membrane, while the two β subunits penetrate the membrane into the cell’s cytoplasm
Binding of insulin to the α-subunits of its receptor leads to activation of the kinase domains and their signaling potential by a process known as ‘receptor oligomerization’
Receptor oligomerization stabilizes all interactions between adjacent cytoplasmic domains of the receptor and controls activation of kinase activity
During receptor oligomerization, there is aggregation of receptors, after which the tyrosine kinase domain of each receptor phosphorylates the tyrosine of neighboring receptors, a process known as autophosphorylation
Apart from autophosphorylation, there are also series of protein phosphorylation activities and signal transduction involving several molecules, including Grb 2, Son of Sevenless (SOS), Insulin Receptor Substrates (IRS), Ras, Raf, Mitogen – Activated Protein Kinase (MAPK), etc., - all of which lead to phosphorylation of transcription factors within the nucleus
This leads to slow changes in the rates of transcription of DNA and translation of mRNAs that code for much of the enzymatic machinery involved in glycogen metabolism