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2. BIOCHEMICAL ROLE OF HORMONES :
1. PANCREAS : pancreas secrete two hormones ,insulin and glucagon .
2. Insulin is secreated by alpha cells of ielts of Langerhans ,was isolated by Banting and Best in 1922 . Insulin is
associated with blood sugar .and has effect on carbohydrate metabolism .insulin affects fat and protein
metabolism .as much as it does carbohydrate metabolism..
3. When there is a large number of carbohydrate or energy giving food ,insulin gets secreted in large quantity .it
stores energy substances. The carbohydrate stores as glycogen in liver and muscle and fat as adipose tissue .
EFFECT ON CARBOHYDRATE METABOLISM :
1. When we take carbohydrate in diet , glucose is absorbed into blood and cause insulin to get secreted. And insulin
helps in rapid uptake ,storage and utilization of glucose by all tissues .glucose enters the all cells by facilitated
diffusion .insulin increases the cell entry by facilitated diffusion .the glucose transporter molecule is called GLUT
4 in liver glucose induce hexokinase and this increases phosphorylation of glucose, as a result the concentration of
intracellular free glucose remain low facilitating the entry of glucose into cell..
2. In a normal person half of glucose is ingested and is converted to energy through glycolytic pathway. And half is
stored as glycogen or fat .glycolysis decreases in the absence of insulin and the anabolic process of glycogenesis
and lipogenesis are affected .only 5 % of an ingested glucose load is converted to fat in an insulin deficient
diabetic.
3. Insulin increases hepatic glycolysis by increasing the activity and amount of severe regulatory enzyme including
Glucokinase , phosphofructokinase-I and pyruvate kinase. increased glycolysis increases glucose utilization and thus
indirectly decreases glucose release into plasma .insulin decreases the activity of glucose 6 phosphatase .this enzyme
is found only in liver ,its absent in muscle. Glucose 6 phosphate cannot cross plasma membrane of the liver cell ,it
result in retention of glucose within liver .i
In liver and muscle ,insulin stimulates the conversion of glucose to glucose 6 phosphate that gets converted to
glucose 1 phosphate .and is incorporated in glycogen by enzyme glycogen synthase. Insulin activates
phosphodiesterase causing hydrolysis and conversion of CAMP TO 5 AMP ,Hence intracellular Camp level
decreased . glycogen synthase remain in dephosphorylated active form promoting glycogen synthase .low level of
CAMP also do not promote phosphorylation of phosphorylase so the net effect is highly anabolic .the glycogen has
total of about 5-6% of liver mass that is equivalent to almost 100 gms of stored glycogen in whole liver. The action
of insulin on glucose transport ,glycolysis and glycogenesis occur within seconds many gluconeogenic enzyme are
activated by glucocorticoid hormone ,vasopressin , angiotensin II . The key gluconeogenic enzyme is
phosphoenolpyruvate carbokinase .
Insulin stimulates lipogenesis from glucose .the net action is to decrease the blood glucose level .
EFFECTS ON LIPID METABOLISM:
1. Lipogenesis is promoted by insulin :
4. by :
1. Providing acetyl COA and NADPH required in fatty acid synthesis.
2. Maintaining a normal level of enzyme acetyl COA carboxylase and providing the glycerol moiety required for
triglycerol synthesis.
The effect of insulin on fat is anabolic .it is inhibitor of lipolysis in liver and adipose tissue and has indirect anabolic
effect .since insulin decreases tissue Camp level ,protein kinase activity is decreased resulting in phosphorylated form
of lipase .This cannot cause hydrolysis of fat .insulin also activates phosphatase as a result of which lipase is
maintained a dephosphorylated inactive form .so it results in decrease in free fatty acid level .,it promotes glucose
utilization .the patients who are suffering from insulin deficiency ,lipase activity increases resulting enhanced lipolysis
and increased free fatty acid in plasma and liver. Insulin affects the formation of VLDL and LDL .these metabolites
are elevated n poorly controlled diabetes .accelerated atherosclerosis ,a serious problem in many diabetics
EFFECT ON PROTEIN METABOLISM :
Insulin has anabolic effect on protein anabolism since it stimulates protein synthesis and retards protein degradation
it increases the uptake of neutral aa into muscle. Mostly alanine,leucine,isoleucine ,tyrosine etc. the effects of insulin
on general protein synthesis in skeletal and cardiac muscle and in liver are thought to be exerted at the level of m
RNA translation .insulin depresses the rate of gluconeogenesis. As aa are the most important substrate for
gluconeogenesis.so suppression of gluconeogenesis conserves the aa in protein stores of body .protein wasting is one
of the wasting serious of all effect of diabetes mellitus.
5. EFFECT ON GROWTH AND SYNERGISTIC EFFECT WITH GROWTH HORMONES:
Insulin is required for synthesis of protein, it is essential for growth .Insulin with growth hormone promote growth .
Insulin deficiency :hyperglycemia occurs during diabetes mellitus. Due to decreased entry of glucose into cells
,decreased utilization of glucose by various tissue, and increased production of glucose by liver .it depicts the
pathophysiology of insulin deficiency.polyuria,and weight loss inspire of adequate caloric intake are major symptoms of
insulin deficiency .High level of blood sugar lead to excretion of sugar in urine .the urine volume is increased due to
osmotic diuresis leading to polyuria and polydipsia. Due to non utilization of glucoses a source of energy that lead to
weight loss
6. Glucagon : it is the hormone secreted by beta cells of islets of Langerhans of pancreas .most important function is
to increase the blood glucose concentration .secretion of glucagon is inhibited by glucose. Insulin promotes energy
storage by stimulating glycogenesis ,lipogenesis and protein synthesis ,glucagon cause mobilization of energy sources.
EFFECT ON GLUCOSE METABOLISM :
1. It breakdown liver glycogen
2. Increase the synthesis of glucose from non carbohydrate sources.
3. The liver is target of glucagon action .
4. It greatly enhance the availiabity of glucose to other organ after glycogenosis the blood glucose concentration
increases with in minutes .
5. As a result of glycogenolysis in liver ,blood glucose concentration increases with in minutes bind to specific
receptors in hepatic cell plasma membrane that result in activation of adenylyl cyclase .Adenylyl cyclase forms
Camp that activates a protein kinase and causes phosphorylation of protein including glycogen phosphorylase .
6. Being active in phosphorylated form ,phosphorylase enhance rate of glycogen degradation releases glucose to
blood
7. Glycogen synthase is also phosphorylated by kinase .synthase is inactive in this form and glycogen synthesis
inhibited. Glucagon adds glucose to blood ,also it prevents glucose from leaving blood from glycogenesis . It
increases the blood sugar concentration .few microgram of glucagon cause blood glucose level to double.
7. Glucagon has no effect on glycogenolysis in muscle tissue. The increased level of Camp following release of glucagon
stimulates the conversion of amino acid to glucose this include regulatory enzyme PEPCK.
EFFECT ON LIPID METAMOBLISM :
1. Glucagon is lipolytic agent.it increase camp level in adipose cell.it causes activation of kinase that phosphorylates
the hormones sensitive enzyme lipase .the lipase hydrolyse the stored fat into components, glycerol and fat. The
fatty acid released are transport to blood for other tissue .excessive breakdown of fatty acid promotes ketogenesis
it leads to ketosis.
THYROID :
1. It produces 2 hormones : triiodothyronine and tetra iodothyronine .and thyroxine.
2. T3 and T4 : They need iodine for biological activity .
3. Calcitonin: it is secreted by thyroid gland.it has week effects on blood calcium but opposite those of
parathormone.it reduces ca+2 concentration by decreasing resorption of blood mineral.it functions to increase
deposition of ca+2and phosphate.
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