INSULIN

Insulin is a peptide hormone produced by beta cells of the islets of langerhan in the pancreas. it is considered to be the main anabolic hormone, and It regulates the metabolism of carobhydrates, fats and proten, by promoting the absorption od glucose from the blood into the liver, skeletal muscle, and fat cells.  In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, and in the case of the liver uses both. Glucose production and secretion by the liver is inhibited strongly by high concentrations of insuin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially of body fat reserves.

Beta cells are sensitive to blood sugar levels so that they secrete insulin into the blood in response to high levels of glucose; and inhibit secretion of insulin when glucose levels are low.

Insulin enhances glucose uptake and metabolism in the cells, thereby reducing blood sugar level. Their neighboring alpha cells, taking their cues from the beta cells, secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high. Glucagon increases blood glucose level by stimulating glycogenolysis, and gluconeogenesis in the liver.The secretion of insulin and glucagon into the blood in response to the blood glucose concentration is the primary mechanism of glucose homeostasis.

Decreased or absent insulin activity results in diabetes mellitus, a condition of high blood sugar level (hyperglycaemia). There are two types of the disease. 

TYPE 1. In type 1, the beta cells are destroyed by an autoimmune response so that insulin can no longer be synthesized or be secreted into the blood.

TYPE 2.  The destruction of beta cells is less pronounced than in type 1 diabetes, and is not due to an autoimmune process. Instead, there is an accumulation of amyloid in the pancreatic islets, which likely disrupts their anatomy and physiology.

The pathogensis of type 2 diabetes reduces the population of islet beta-cells, reduced secretory function of islet beta-cells that survive, and peripheral tissue insulin resistance are known to be involved.

Type 2 diabetes is characterized by increased glucagon secretion which is unaffected by, and unresponsive to the concentration of blood glucose. But insulin is still secreted into the blood in response to the blood glucose. As a result, glucose accumulates in the blood.                  

PHYSIOLOGICAL EFFECTS

The actions of insulin on the global human metabolism level include:

• Increase of cellular intake of certain substances, most prominently glucose in muscle and adipose tissue, (about two-thirds of body cells)
• Increase of DNA replication and protein synthesis, via control of amino acid uptake
• Modification of the activity of numerous enzymes.

THE ACTIONS OF INSULIN (INDIRECT AND DIRECT) ON CELLS INCLUDE:

• Stimulates the uptake of glucose – Insulin decreases blood glucose concentration by inducing intake of glucose by the cells. This is possible because Insulin causes the insertion of the GLUT4 transporter in the cell membranes of muscle and fat tissues which allows glucose to enter the cell.
• Increased fat synthesis – insulin forces fat cells to take in blood glucose, which is converted into triglycerides; decrease of insulin causes the reverse.
• Increased esterification of fatty acids – forces adipose tissue to make neutral fats (i.e. triglycerides) from fatty acids; decrease of insulin causes the reverse.
• Decreased lipolysis – forces reduction in conversion of fat cell lipid stores into blood fatty acids and glycerol; decrease of insulin causes the reverse.
• Induce glycogen synthesis – When glucose levels are high, insulin induces the formation of glycogen by the activation of the hexokinase enzyme, which adds a phosphate group in glucose, thus resulting in a molecule that cannot exit the cell. At the same time, insulin inhibits the enzyme glucose-6-phosphatase, which removes the phosphate group. These two enzymes are key for the formation of glycogen. Also, insulin activates the enzymes phosphofructokinase and glycogen synthase which are responsible for glycogen synthesis.
• Decreased gluconeogensis and glycogenolysis – decreases production of glucose from noncarbohydrate substrates, primarily in the liver (the vast majority of endogenous insulin arriving at the liver never leaves the liver); decrease of insulin causes glucose production by the liver from assorted substrates.
• Decreased proteolysis – decreasing the breakdown of protein
• Decreased autophagy – decreased level of degradation of damaged organelles. Postprandial levels inhibit autophagy completely.
• Increased amino acid uptake – forces cells to absorb circulating amino acids; decrease of insulin inhibits absorption.

• Arterial muscle tone – forces arterial wall muscle to relax, increasing blood flow, especially in microarteries; decrease of insulin reduces flow by allowing these muscles to contract.
• Increase in the secretion of hydrochloric acid by parietal cells in the stomach.
• Increased potassium uptake – forces cells synthesizing glycogen (a very spongy, "wet" substance, that increases the content of intracellular water, and potassium ions to absorb potassium from the extracellular fluids; lack of insulin inhibits absorption. Insulin's increase in cellular potassium uptake lowers potassium levels in blood plasma. This possibly occurs via insulin-induced translocation of the Na+/K+-ATPase to the surface of skeletal muscle cells.
• Decreased renal sodium excretion.

Insulin also influences other body functions, such as vascular compliance and cognition. Once insulin enters the human brain, it enhances learning and memory and benefits verbal memory in particular. Enhancing brain insulin signaling by means of intranasal insulin administration also enhances the acute thermoregulatory and glucoregulatory response to food intake, suggesting that central nervous insulin contributes to the co-ordination of a wide variety of homeostatic regulatory processes in the human body. Insulin also has stimulatory effects on gonadothrophic releasing hormone thus favoring fertility. Once insulin molecules have docked onto the receptor and effected its action, it may be released back into the extracellular environment, or it may be degraded by the cell. The two primary sites for insulin clearance are the liver and the kidney. The liver clears most insulin during first-pass transit, whereas the kidney clears most of the insulin in systemic circulation.