PANCREAS & ITS HORMONES

PANCREAS & ITS HORMONES

PANCREAS

·     Pancreas in an organ that lies at the upper left abdomen.

·     Pancreas is made up of two major types of cells.

ü Acini-which secretes digestive juice into the duodenum.

ü Islets of Langerhans –which secretes hormones.

(25%)α Islets of Langerhans – Glucagon.

(60%)β Islets of Langerhans – Insulin.

(15%)δ Islets of Langerhans – Somatostatin.

       INSULIN:

vInsulin is a protein hormone secreted by β cells of islets of Langerhans of pancreas.

   Chemistry:

vMolecular weight around 6000 Daltons.

vIt consist of 2 polypeptide chains-A chain & B chain.

vA chain has 21 amino acids & B chain has 30 amino acids.

vA chain & B chain are connected by 2 inter disulphide bridges at cysteine 7 of A chain and cysteine 7 of B chain and cysteine 20 of A chain and 19 of B chain.

v‘A’ chain has intra disulphide bridge between cysteine 6 & cysteine 11.

Biosynthesis of Insulin

-      Insulin is synthesized in significant quantities only in beta cells in the pancreas.

-      The insulin mRNA is translated as a single chain precursor called preproinsulin,

-      The removal of its signal peptide during insertion into the endoplasmic reticulum generates proinsulin.

-      Proinsulin consists of three domains: an amino-terminal B chain, a carboxy-terminal A chain and a connecting peptide in the middle known as the C peptide.

-      Within the endoplasmic reticulum, proinsulin is exposed to several specific endopeptidases which excise the C peptide, thereby generating the mature form of insulin.

-       Insulin and free C peptide are packaged in the Golgi into secretory granules which accumulate in the cytoplasm.

-      When the beta cell is appropriately stimulated, insulin is secreted from the cell by exocytosis and diffuses into islet capillary blood.

-      C peptide is also secreted into blood, but has no known biological activity.

 

Secretions:

vInsulin is secreted in response to glucose(i.e)

                          [8 m mol/L (145mg/dl) ]

vIn fasting - ≤ 25 m IU/L of Insulin is secreted.

(30 min after glucose = 30 – 230m IU/L)

vInsulin secretion is stimulated by glucose in 2 phases.

  Functions:

1.  Lowering of blood glucose level by

ü Increasing glycogenesis.

ü Increasing glycolysis.

ü Increasing HMP shunt.

ü Increasing glucose uptake by various tissues.

ü Decreases glycogenolysis.

ü Decreases gluconeogenesis

2.  Lowering of free fatty acids by

ü Decreasing lipolysis.

ü Increases TG synthesis.

ü Decreases ketogenesis.

3.  Promotes protein synthesis.

4.  Decreases concentration of potassium and phosphorous in blood.

5.  Stimulates cell proliferation & growth.

  Regulation Of Insulin Secretion:

vInsulin secretion primarily controlled & regulated by glucose concentration in blood.

(i.e) plasma concentration of insulin almost increases 10 fold within 3 to 5 min after acute elevation of the blood glucose.

vInsulin secretion is also regulated by other factors as follows.

Increases insulin secretion:

·     Increased blood glucose.

·     Increased blood free fatty acids.

·     Increased blood amino acids

·     Glucagon, Growth hormone, cortisol.

·     Acetyl choline.

Decreases insulin secretion:

·     Decreased blood glucose.

·     Fasting.

·     Somatostatin.

GLUCAGON

vIt is also called as hyperglycemic hormone.

vIt is secreted by α islets of Langerhans of pancreas.

   Chemistry

       Glucagon has 3485 Daltons of molecular weight.

ü Is is a polypeptide containing 29 amino acid with histidine in N – terminal & threonine in C- terminal.

H2N-His------------------------------------Thr-cooH.

                             29 Aminoacid

   Secretion

v When glucose levels in the blood stream drop, the β cells of pancreas stop secreting insulin & α cells of pancreas releases glucagon.

vNormal glucagon level range in fasting-50-100pg/m[50-100pg/ml]

Functions

vIncreases blood glucose levels by

ü Increasing glycogenolysis.

ü Increasing gluconeogenesis.

ü Decreasing Glycolysis

ü Decreasing Glycogenesis.

vIncreases lipolysis (i,e) triglyceride breakdown to fatty acid and glycerol.

vDecreases fattyacid/ lipid synthesis.

vDecreases protein synthesis.

vIncreases protein catabolism.

vGlucagon increases heat production & rise in BMR.

vGlucagon increases potassium release from the liver.

vGlucagon exerts positive ionotropic effect (force of heart contraction) on heart (hence used in treatment of heart tissues (i,e) heart failure & in cardiogenic shock.

Regulation Of Glucagon Secretion