Pancreas

Biochemistry

2nd stage
Dr.Lamees Majid Al-Janabi

The Pancreas

is a mixed glandular organ (has both endocrine secretions [like the insulin H] and exocrine secretions [Hormones to the digestive system], In humans, it is located in the abdominal cavity behind the stomach. It consist of head ,neck ,body and tail.

The pancreas as endocrine gland

The endocrine function of the pancreas consists of the islets of Langerhans, producing several important hormones, including insulin, glucagon, somatostatin, and pancreatic polypeptide, all of which circulate in the blood.

Cell type

Relative abundance

Hormone produced

A ( α )

~ 25 %

Glucagon

B ( β)

~ 70 %

Insulin

D ( δ)

< 5%

Somatostatin

F (PP)

Trace

Pancreatic polypeptide

Enterochromaffin


Serotonin

Serotonin

Insulin
Is a polypeptide consisting of 2 chains , A ( contains 21 amino acids) and B ( contains 30 amino acids).
It is synthesized as a preprohormone from which a sequence of 23 amino acids removed to form a proinsulin which undergoes a series of site specific peptide cleavage that result in the formation of mature insulin and C- peptide.
C – peptide has no Known biological activity, but it carry a valuable diagnostic significance to distinguish endogenous from exogenous insulin secretion.

Regulation of insulin secretion

A:- Glucose :-
An increase in plasma glucose concentration is the most important physiological regulator of insulin secretion. The maximal response is obtained at glucose levels between 300-500 mg/dl.
Mechanisms :-
1. Glucose combines with receptors possibly located on β- cell membrane that activate release mechanism.
2. Intracellular metabolites or the rate of metabolic flux through pathways such pentose phosphate pathway, citric acid cycle or glycolytic pathway are involved.

B:- Hormonal factors:-

Insulin release is inhibited by &2 - adrenergic agonists, but stimulated by β2 – adrenergic agonists.
Chronic exposure to excessive levels of GH, cortisol, placental lactogen , oestrogens and progesterone also stimulate insulin secretion.


C:- Phormacological agents :-
Insulin release is stimulated by certain drugs example Sulphonylureas ex: Glibenclamide.
Effects of Insulin:
1. On CHO metabolim: Insulin ↓ blood glucose level by :-
↑glucose entry into skeletal muscle and adipose tissue.
↑ glycogen synthesis in the liver and skeletal muscle.
↑ Hepatic glycolysis
Inhibition of gluconeogenesis
Inhibition of glucose – 6 – phosphatase activity.

2. On lipid metabolism:- Insulin stimulate lipogenesis and inhibits lipolysis.

3. On protein metabolism:- Insulin stimulate protein synthesis and retards protein degredation.
4. Effect on cell replication:- Insulin stimulate cell proliferation in culture , and may be involved in growth regulation invivo.

Pathophysiology of glucose metabolism

Insulin deficiency (whether absolute or relative) results in Diabetes mellitus “ DM” , the incidence of which is dramatically increasing elsewhere in the world.
Generally DM is usually divided into 2 main types:
1. Type 1 diabetes ( T1D ). Most of these cases are due to immune-mediated processes
2. Type 2 diabetes ( T2D ). There is a spectrum of disorders ranging from mainly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance.

Glucagon:

Is a single polypeptide consists of 29 amino acids synthesized as proglucagon precursor. glucagon secretion is inhibited by glucose.
The role of Glucagon
1-Glucagon generally elevates the concentration of glucose in the blood
by promoting gluconeogenesis and glycogenolysis.
2- Glucagon also decrease fatty acid synthesis in adipose tissue and the liver as
well as promoting lipolysis in these tissues which causes them to release fatty acids into circulation where they can be used to generate energy in tissues such as skeletal muscle when required.

Somatostatin

Is a cyclic peptide synthesized as large somatostatin prohormone. Also , it is secreted from the hypothalamus and gastrointestinal tissues.
Effects:
Somatostatin suppresses the release of gastrointestinal Hormones Gastrin ,Cholecystokinin (CCK) ,Secretin , Motilin, Vasoactive intestinal peptide (VIP), Gastric inhibitory polypeptide (GIP), Enteroglucagon.
Decrease rate of gastric emptying, and reduces smooth muscle contractions and blood flow within the intestine.
Suppresses the release of pancreatic hormones.
Suppresses the exocrine secretory action of pancreas.
Pathophysiology
1-The excess levels of somatostatin may cause abdominal cramps and pain,
persistent diarrhea, high blood glucose concentrations, weight loss, and episodic flushing of nthe skin.
2-somatostatin deficiency have been found in Alzheimer disease.

Pancreatic Polypeptide “ PP”

Is a 36 aminoacid peptide.

PP secretion is increased by:

protein meal, fasting , exercise, and acute hypoglycaemia.

PP secretion is decreased by:

by somatostatin and intravenous glucose.


Function of PP: unknown, but it may affect hepatic glycogen levels and gastrointestinal secretion.