Insuline Hormone
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Transcript of 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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Metabolic Effects of Insulin
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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Metabolic Effects of Insulin
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)