THE ENDOCRINE THE ENDOCRINE PANCREAS:PANCREAS:

Located partially behind the stomach, Located partially behind the stomach, the pancreas is a mixed gland composed the pancreas is a mixed gland composed of both endocrine and exocrine cells. of both endocrine and exocrine cells.

More than 98% of the gland is made up More than 98% of the gland is made up of acinar cells producing an enzyme-rich of acinar cells producing an enzyme-rich juice that enters a system of ducts and juice that enters a system of ducts and is delivered to the duodenum of the is delivered to the duodenum of the small intestine during food digestion. small intestine during food digestion.

The remaining 1-2% of cells form about The remaining 1-2% of cells form about 1 million of islets of Langerhans, tiny 1 million of islets of Langerhans, tiny cell clusters that produce pancreatic cell clusters that produce pancreatic hormones. hormones.

The islets have four distinct populations The islets have four distinct populations of cells, the two most important ones are of cells, the two most important ones are alpha cells that produce hormone alpha cells that produce hormone glucagon, and more numerous beta cells glucagon, and more numerous beta cells that synthesize insulin. In addition, delta that synthesize insulin. In addition, delta cells produce somatostatin and F cells cells produce somatostatin and F cells secrete pancreatic polypeptide (PP). secrete pancreatic polypeptide (PP).

Hormones of the Hormones of the Pancreas:Pancreas: Glucagon and insulin are directly responsible for the Glucagon and insulin are directly responsible for the

regulation of blood glucose levels and their effects regulation of blood glucose levels and their effects are exactly opposite: are exactly opposite:

insulin is hypoglycemic (it decreases blood glucose)insulin is hypoglycemic (it decreases blood glucose)

glucagon is hyperglycemic (it increases blood glucagon is hyperglycemic (it increases blood glucose). glucose).

Pancreatic somatostatin inhibits the release of both Pancreatic somatostatin inhibits the release of both insulin and glucagon and slows the activity of the insulin and glucagon and slows the activity of the digestive tract.digestive tract.

PP regulates secretion of pancreatic digestive PP regulates secretion of pancreatic digestive enzymes and inhibits release of bile by the enzymes and inhibits release of bile by the gallbladder.gallbladder.

Glucagon:Glucagon:

Glucagon is a 29 amino acid polypeptide with Glucagon is a 29 amino acid polypeptide with extremely potent hyperglycemic properties. extremely potent hyperglycemic properties. One molecule of this hormone can induce the One molecule of this hormone can induce the release of 100 million molecules of glucose release of 100 million molecules of glucose into the blood. into the blood.

The major target organ of glucagon is the The major target organ of glucagon is the liver, where it promotes:liver, where it promotes:

Breakdown of glycogen to glucose (glycogenolysis)Breakdown of glycogen to glucose (glycogenolysis) Synthesis of glucose from lactic acid and from Synthesis of glucose from lactic acid and from

noncarbohydrate molecules such as fatty acids and noncarbohydrate molecules such as fatty acids and amino acids (referred to asgluconeogenesis).amino acids (referred to asgluconeogenesis).

Release of glucose into the blood by the Release of glucose into the blood by the liverliver

All these effects increase blood sugar All these effects increase blood sugar levels.levels.

Secretion of glucagon from the alpha cells is Secretion of glucagon from the alpha cells is induced by, most importantly, low blood induced by, most importantly, low blood sugar levels but also by high amino acid sugar levels but also by high amino acid levels in the blood (e.g. following a protein-levels in the blood (e.g. following a protein-rich meal). Rising blood sugar concentration rich meal). Rising blood sugar concentration and somatostatin from the delta cells inhibit and somatostatin from the delta cells inhibit glucagon release.glucagon release.

Insulin:Insulin:

Insulin is a 51 amino acid protein Insulin is a 51 amino acid protein consisting of two polypeptide chains linked consisting of two polypeptide chains linked by disulfide bonds. It is synthesized as part by disulfide bonds. It is synthesized as part of a larger molecule called proinsulin and of a larger molecule called proinsulin and packed into secretory vesicles where its packed into secretory vesicles where its middle portion is excised by enzymes to middle portion is excised by enzymes to produce functional hormone, just before produce functional hormone, just before insulin is released from the beta cell. insulin is released from the beta cell.

As mentioned earlier, insulin's main As mentioned earlier, insulin's main function is to lower blood sugar levels but function is to lower blood sugar levels but it also affects protein and fat metabolism. it also affects protein and fat metabolism.

In general, insulin:In general, insulin:

Increases membrane transport of glucose Increases membrane transport of glucose into body cells, especially muscle and liver into body cells, especially muscle and liver cellscells

Inhibits the breakdown of glycogen (it Inhibits the breakdown of glycogen (it should not be confused with glucagon!) into should not be confused with glucagon!) into glucose,glucose,

Increases the rate of ATP production from Increases the rate of ATP production from glucoseglucose

Increases the rate of glycogen synthesisIncreases the rate of glycogen synthesis Increases the rate of glucose conversion to Increases the rate of glucose conversion to

fat.fat.

Insulin binds to tyrosine kinase receptors, but Insulin binds to tyrosine kinase receptors, but mechanism of action, including type(s) and mechanism of action, including type(s) and specific roles of second messengers, are poorly specific roles of second messengers, are poorly understood. understood.

The beta cells are stimulated to produce insulin The beta cells are stimulated to produce insulin primarily by elevated blood sugar levels, but also primarily by elevated blood sugar levels, but also by high blood levels of amino acids and fatty by high blood levels of amino acids and fatty acids. acids.

Several hormones also induce the release of Several hormones also induce the release of insulin, including glucagon, epinephrine, growth insulin, including glucagon, epinephrine, growth hormone, thyroid hormones, and glucocorticoids. hormone, thyroid hormones, and glucocorticoids.

In contrast, somatostatin inhibits insulin release.In contrast, somatostatin inhibits insulin release.

Gastric hormones:Gastric hormones: