Insuline Hormone

8/13/2019 Insuline Hormone

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Insuline Hormonerd groupNinda Ramadani Herli NasutionRetno HandayaniSahid Hidayat


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Insulin

The ONLY hormone capable of lowering bloodglucose

Secreted by pancreatic cells in response toelevated blood glucose levels

Increases transport of glucose to muscle, liverand adipose tissue (what lowers blood glucoselevels)

insulin inhibits Glucagon secretion,andsomatostatin inhibits the secretion of both insulinand Glucagon


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insulin gene encodes a large precursor of insulin(preproinsulin)

During translation, the signal peptide is cleaved

(proinsulin) After cleavage of signal sequence proinsulin folds

and forms S-S bonds

In proinsulin A and B chains are connected by a Cpeptide

Cleavage of C peptide forms final product

Insulin Synthesis


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When the glucose concentration is low, insulin

secretion is suppressed and fat is used almostexclusively for energy everywhere except inthe brain tissue.

When the glucose concentration is high,insulin secretion is stimulated andcarbohydrate is used instead of fat, and theexcess blood glucose is stored in the form of

liver glycogen, liver fat, and muscle glycogen .


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Insulin

A small protein, 5.8 kDa

Important in glucose metabolism

Mature insulinA larger precursor

preproinsulin

Remove a 23 aa signal

sequence

Formation of three

disulfide bonds

Proinsulin

Remove the C peptide

Mature insulin

A and B chains.


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Metabolic Effects of Insulin

Energy storage Liver

Promotes anabolism:

glycogen synthesis and storage

Inhibits glycogen breakdown Promotes glycolysis

Inhibits gluconeogenesis

Increases protein, triglyceride and VLDL formation

Inhibits catabolism Decrease hepatic glycogenolysis, ketogenesis and

gluconeogenesis


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Muscle

Promotes protein synthesis

Increased amino acid transport

Stimulating ribosomal protein synthesis

Promotes glycogen synthesis

Enhanced by increased glucose transport into cells

Enhanced activity of glycogen synthase

Inhibiting activity of glycogen phosphorylase

Increased glucose transport into muscle cells


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Adipose tissue

Promotes triglyceride storage

Increased production of lipoprotein lipase Hydrolysis of triglycerides from circulating lipoproteins

Increasing glucose transport into fat cells

Increased cellular levels of alpha-glycerol phosphateesterification of fatty acids to triglycerides

Inhibition of intracellular lipolysis (lipase)


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Factors and conditions that increase and decrease insulin

secretion

decrease insulin secretionIncrease insulin secretion

-Decrease blood glucose

-fasting

-somatostatin

-Alfa-adrenergic activity

-increase blood glucose

-increase blood free fatty acid

-increase blood amino acid

-gastrointestinal hormones (gastrin,

choleccystokinin ,secretin, gastric

inhibitory peptide )

-glucagon, growth hormone, cortisol.

-parasympathetic stimulation-insulin resistance ;obesity


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Insulin is a hormone associated with energy

abundance

Increased ingested carbohydrate , increasesglycogen storage in the liver and muscles .Although all the excess carbohydrate that cannotbe stored as glycogen are converted under the

stimulus of insulin into fats and stored in theadipose tissue .

Increased ingested proteins , increases insulinsecretion to enhance amino acid uptake by cells

and conversion of these amino acids into protein,in addition ,it inhibits the breakdown of theproteins that are already in the cells.


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When insulin is secreted into the blood ,its circulatedalmost entirely in an unbound form ;it has plasma halflife averages only about 6 minutes ,so that it is mainlycleared from the circulation with 10-15 minutes .

Except for the portion of the insulin that combines withreceptors in the target cells ,the remained is degradedby the enzyme insulinase mainly in the liver ,to a lesserextent in the kidneys and muscles .


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The end effects of insulin stimulation are the following :

1- within seconds after insulin binds with its membranereceptors , the membrane of about 80% of the bodys cellsmarkedly increase their uptake of glucose .this isespecially true of muscle cells and adipose cells but not

true of most neurons in the brain .2- the cell membrane becomes more permeable to many ofamino acids ,potassium ions ,and phosphate ions ,causingincreased transport of these substances into cells .


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Storage of glycogen in muscles

If the muscles are not exercising after a meal and yet

glucose transport into the muscle cells in abundance

,then most of the glucose is stored in the form ofmuscle glycogen instead of being used for energy

,up to a limit of 2 to 3 % concentration .the glycogen

can later be used for energy by the muscle .


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Effects of insulin on carbohydrate metabolism

Insulin increases glucose transport into and glucose usageby most other cells of the body (with the exception of brain

cells) in the same way that it affects glucose transport and

usage in the muscle cells .

The transport of glucose into adipose cells mainly provides

substrate for the glycerol portion of the fat molecule .

Therefore ,in this indirect way ,insulin promotes deposition

of fat in these cells.


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Glucagon


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Glucagon and its functions

Glucagon ,a hormone secreted by the alpha cells of the isletsof Langerhans ,when the blood glucose concentration falls.

has several functions that are diametrically opposed to those

of insulin .Most important of these functions is to increase

the blood glucose concentration ,an effect that is exactly theopposite that of insulin

Like insulin ,glucagon is a large polypeptide .it has a

molecular weight of 3485 and is composed of a chain of 29

amino acids

glucagon is also called the hyperglycemic hormone.


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Effects on glucose metabolism

The major effects of glucagon on glucose metabolism :

1- breakdown of liver glycogen (glycogenolysis)

2- increased gluconeogenesis in the liver

* Both of these effects greatly enhance the availability ofglucose to the other organs of the body.

* Glucagon causes glycogenolysis and increased blood

glucose concentration:

* The most dramatic effect of glucagon is it's ability to cause

glycogenolysis in the liver ,which in turn increase the blood

glucose concentration within minutes


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Regulation of glucagon secretion

- Increased blood glucose inhibits glucagon secretion :

- increase blood amino acids stimulate glucagon secretion

:

High concentrations of amino acids as occur in the bloodafter protein meals stimulate the secretion of glucagon .this

is the same effect that amino acids have in stimulating

insulin secretion.

Thus in this instance the glucagon and insulin responses arenot opposite.

- exercise stimulates glucagon secretion.


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-exercise stimulates glucagon secretion :In exhaustive exercise, the blood concentration of glucagon

often increases fourfold to fivefold. A beneficial effect of

the glucagon is that to prevents a decrease in blood

glucose

One of the factors that might increase glucagon secretion in

exercise is increased circulating amino acids .other

factors such as betaadrenergic stimulation of the isletsof langerhans ,may also play a role .


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SYNTHESISDNA in cells

mRNA

Preproglucagon

proglucagon

glucagon

Gl A ti C ll


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Glucagon Action on Cells:


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iabetes Melitus


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Diabetes mellitus

Is a syndrome of impaired carbohydrate ,fat, and proteinmetabolism caused by either lack of insulin secretion ordecreased sensitivity of the tissue to insulin

There are two types of diabetes mellitus

1-type 1 diabetes also called insulindependent diabetesmellitus (IDDM) is caused by lack of insulin secretion

2-type 2 diabetes mellitus also called non-insulin-dependent diabetes mellitus (NIDDM) is caused by

decrease sensitivity of target tissue to the metaboliceffects of insulin (also called insulin resistance )


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Clinical characteristics of patients with type 1 and type 2

diabetes mellitus

Type 2type1feature

Usually more than 30

Obese

Normal to high initially

High ,resistant to

suppression

IncreaseReduce

Weight loss,

thiazolidinediones

Metformin

,sulfonylureas,insulin

Usually


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Diabetes Mellitus: Type II a Group of

Diseases


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Diabetes Mellitus (DM)

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Insuline Hormone