ENDOCRINOLOGY Lec. 8 Dr. Ali al-bayati - PowerPoint Presentation

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ENDOCRINOLOGY

Lec. 8

Dr. Ali al-bayati

Hormones of the pancreas and GIT

the pancreas

DEFINITION

The

pancreas (pan= all ,

kreas

= flesh) is

a gland that is

partly exocrine and

partly endocrine.

The

exocrine part secretes

the digestive

pancreatic juice, and the

endocrine part

secretes hormones,

eg

. Insulin.

The endocrine pancreasDistributed throughout the gland are groups of specialised

cells called the pancreatic islets (islets of Langerhans).The endocrine pancreas secretes the hormones insulin and glucagon, which are

principally concerned with control of blood glucose levels.

The islets containing

four different types of cells that secreted different

hormones

, In order of abundance, they are the:

Beta

cells, which secrete

insulin

and amylin.

alpha

cells, which secrete

glucagon

;

delta

cells, which secrete

somatostatin

Gamma

cells, which secrete

pancreatic polypeptide (PP)

.

Insulin

Is a polypeptide hormone produce by

β-cells of Langerhans

It has profound on

metabolism

of Carbohydrates

, fat & proteins.

It

is considered as the anabolic hormone.

It was the first hormone to be isolated,

purified & synthesized.

First

hormone to be sequenced

First hormone to be produced by recombinant DNA technology.

Two Interchain Disulfide bridge = A7-B7

& A20-B19

.

Intrachain

Disulfide link in chain A = 6-11.

• Gene for protein synthesis is located on Chr 11• Produced from

β-cell of Langerhans of pancreas.• Synthesis involve two precursors– Preproinsulin = 108AA– Proinsulin = 86 AA

Synthesis

These are sequentially degraded to form

the active

hormone Insulin

and

Connecting peptide

(C-Peptide)

C-peptide

has no biological activity,

however its

estimation in plasma serves as the

useful index for endogenous production of insulin.• In β-cells, Insulin combines with Zinc to form a complex & stored in granules.Regulation of Insulin secretion• About 40-50Units secreted daily by Human pancreas

.

•

Normal value is = 20-30

μ

U/mL

Insulin Secretion

Factors Increased secretion;

insulin secretion is increased by glucose, amino acids, and gastrointestinal peptide hormones.

Glucose: Type 2 glucose transporters (

GLUT2

) mediate the entry of glucose into beta cells.

Amino acids:

Ingestion of protein causes a transient rise in plasma amino acid levels (for example, arginine) that enhances the glucose stimulated secretion of insulin.

Gastrointestinal peptide hormones:

(

GLP-1) and gastric inhibitory polypeptide ([GIP] increase the sensitivity of β cells to glucose.

Their

action may account for same amount of glucose given orally induces a much greater secretion of insulin than if given

intravenously (

IV).

Mechanism of glucose stimulated insulin secretion;

oral agents used to treat type 2 diabetes

, increase insulin secretion by closing ATP-sensitive K+ channels.

Degradation of Insulin

• Half life is 4-5mins.• A protease enzyme, namely insulinase degrades Insulin (mainly found in liver andkidney)

GlucagonGlucagon is a peptide hormone secreted by the α cells of the pancreatic islets of Langerhans.

Glucagon, along with epinephrine, norepinephrine, cortisol, and growth hormone (the counter regulatory hormones)

Cellular mechanism of action of glucagon;

Glucagon binds to high-affinity G protein–coupled receptors on the cell membrane of hepatocytes. Binding results in the activation of adenylyl cyclase, which produces the second, messenger cyclic adenosine monophosphate (cAMP). Subsequent activation of cAMP dependent

protein kinase A results in the phosphorylation-mediated activation or inhibition of key regulatory enzymes involved in carbohydrate and lipid metabolism.

Delta CellsThe delta cells secrete somatostatin. This consists of two polypeptides, one of 14 amino acids and one of 28. Somatostatin has a variety of functions. Taken together, they work to reduce the rate at which food is absorbed from the contents of the intestine. Somatostatin is also secreted by the hypothalamus and by the intestine.

Gamma CellsThe gamma cells of the islets secrete a 36-amino-acid pancreatic polypeptide. Its function is to self-regulate the pancreas secretion activities. It also has effects on hepatic glycogen levels and gastrointestinal secretions. Its secretion human is increased after a protein meal, fasting, exercise and acute hypoglycemia and is decreased by somatostatin.,.

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