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genefegan

Insulin?

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Cormac_Doyle

Special transporter proteins in cell membranes allow glucose from the blood to enter a cell. These transporters are, indirectly, under blood insulin's control in certain body cell types (e.g., muscle cells and adipose {fat} cells).

 

Low levels of circulating insulin, or its absence, will prevent glucose from entering those cells (e.g., in type 1 diabetes). More commonly, however, there is a decrease in the sensitivity of cells to insulin (e.g., the reduced insulin sensitivity characteristic of type 2 diabetes), resulting in decreased glucose absorption.

 

In either case, there is 'cell starvation' and weight loss, sometimes extreme. In a few cases, there is a defect in the release of insulin from the pancreas. Either way, the effect is the same: elevated blood glucose levels.

 

Two types of tissues are most strongly influenced by insulin, as far as the stimulation of glucose uptake is concerned: muscle cells (myocytes) and fat cells (adipocytes). The former are important because of their central role in movement, breathing, circulation, etc., and the latter because they accumulate excess food energy against future needs. Together, they account for about two-thirds of all cells in a typical human body.

 

Insulin binds to the extracellular portion of the alpha subunits of the insulin receptor. This, in turn, causes a conformational change in the insulin receptor that activates the kinase domain residing on the intracellular portion of the beta subunits. The activated kinase domain autophosphorylates tyrosine residues on the C-terminus of the receptor as well as tyrosine residues in the IRS-1 protein.

 

phosphorylated IRS-1, in turn, binds to and activates phosphoinositol 3 kinase (PI3K)

PI3K catalyzes the reaction PIP2 + ATP → PIP3 + ADP

PIP3 activates protein kinase B (PKB)

PKB phosphorylates glycogen synthase kinase (GSK) and thereby inactivates GSK

GSK can no longer phosphorylate glycogen synthase (GS)

unphosphorylated GS makes more glycogen

PKB also facilitates vesicle fusion, resulting in an increase in GLUT4 transporters in the plasma membrane

 

After the signal has been produced, termination of signaling is then needed. Endocytosis and degradation of the receptor bound to insulin is a main mechanism to end signaling. In addition, signaling can be terminated by dephosphorylation of the tyrosine residues by tyrosine phosphatases. Serine/Threonine kinases are also known to reduce the activity of insulin. Finally, with insulin action being associated with the number of receptors on the plasma membrane, a decrease in the amount of receptors also leads to termination of insulin signaling.

 

The actions of insulin (indirect and direct) on cells include:

* Increased glycogen synthesis – insulin forces storage of glucose in liver (and muscle) cells in the form of glycogen; lowered levels of insulin cause liver cells to convert glycogen to glucose and excrete it into the blood. This is the clinical action of insulin, which is directly useful in reducing high blood glucose levels as in diabetes.

* Increased lipid synthesis – insulin forces fat cells to take in blood lipids, which are converted to triglycerides; lack of insulin causes the reverse.

* Increased esterification of fatty acids – forces adipose tissue to make fats (i.e., triglycerides) from fatty acid esters; lack of insulin causes the reverse.

* Decreased proteolysis – decreasing the breakdown of protein

* Decreased lipolysis – forces reduction in conversion of fat cell lipid stores into blood fatty acids; lack of insulin causes the reverse.

* Decreased gluconeogenesis – decreases production of glucose from nonsugar substrates, primarily in the liver (the vast majority of endogenous insulin arriving at the liver never leaves the liver); lack of insulin causes glucose production from assorted substrates in the liver and elsewhere.

* Decreased autophagy - decreased level of degradation of damaged organelles. Postprandial levels inhibit autophagy completely. (Autophagy is an important component of the body's response to aging and damaged tissue; without it, cancer is dramatically more likely ... consistently high levels of insulin therefore make cancer more likely !!! )

* Increased amino acid uptake – forces cells to absorb circulating amino acids; lack of insulin inhibits absorption.

* Increased potassium uptake – forces cells to absorb serum potassium; lack of insulin inhibits absorption. Insulin's increase in cellular potassium uptake lowers potassium levels in blood. This possibly occurs via insulin-induced translocation of the Na+/K+-ATPase to the surface of skeletal muscle cells.

* Arterial muscle tone – forces arterial wall muscle to relax, increasing blood flow, especially in microarteries; lack of insulin reduces flow by allowing these muscles to contract.

* Increase in the secretion of hydrochloric acid by parietal cells in the stomach (high levels of circulating insulin will cause heart burn and ulcers ...)

* Decreased renal sodium excretion (thus increasing blood pressure)

 

===================================

 

Drugs such as Actos and Avandia increase the insulin signalling by partially activating the pathway above; thus it requires less inulin to trigger the GLUT4 transporters.

Drugs such as Glip or the sulpha drugs increase the output of insulin from the pancreas

Drugs such as Metformin primarily target the insulin/glucagon feedback mechanisms in the liver

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rzrbks

goes in and pounds the sugar molecules into shapes where they'll fit into the receptors and your body gets to use them and send many to your brain, which, does run on carbs.

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Cormac_Doyle
goes in and pounds the sugar molecules into shapes where they'll fit into the receptors and your body gets to use them and send many to your brain, which, does run on carbs.

 

Technically it goes in and changes the shape of the receptor ;)

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JJM335
Technically it goes in and changes the shape of the receptor ;)

 

Technically it binds to the receptor activating a signaling response within the cell. This stimulates vesicles containing the GLUT4 glucose transporter to be trafficked to the plasma membrane that encloses the cell - there they merge with the plasma membrane. The GLUT4 transporters are now embedded within the plasma membrane where they are able to transport glucose molecules from outside the cell, across the plasma membrane into the cell. NET RESULT - glucose moves from outside to inside the cell.

 

Receptor binding also stimulates the production of more GLUT4 molecules.

 

Joel

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mjc1991

it opens your cells to uptake glucose to provide your body with energy instead of letting your glucose build up in the bloodstream.

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TX_Clint
goes in and pounds the sugar molecules into shapes where they'll fit into the receptors and your body gets to use them and send many to your brain, which, does run on carbs.

 

Ergo... if I didn't have diabetes and eat a LC/HF diet I'd be a genius. :stupido3:

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GretchO
...your brain, which, does run on carbs.

 

the brain uses glucose, doesn't have to be from carbs.

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