26
Lec. 8: Pancreatic hormones
The pancreases' is an intra-abdominal organ, it has endocrine and exocrine parts,
The exocrine part is responsible for the production and releases of digestive enzymes
The endocrine part (the islets of Langerhans) secrets hormones, There are four major
cell types in the islets of Langerhans:
1) α cell, responsible for the production of glucagon.
2) β-cell for production of insulin,
3) δ (Delta)-cell for production of somatostatin, and
4) F (or PP) cell responsible for the production of pancreatic polypeptide.
Insulin
Is a peptide hormone made up of 51 amino acids, arranged as two polypeptide chains, the
A chain has 21 amino acids and is linked to the B chain (30 a.a) by two disulfide bridges.
Biosynthesis of insulin occurs from a precursor called preproinsulin (109 aminoacids),
which consists of proinsulin plus an extension of 23 amino acids. It is cleaved by
peptidase, and converted to proinsulin (86AA). proinsulin is a single polypeptide, It has
A and B chains, the A chain is linked to the B chain by a connecting peptide (C-peptide),
then Proinsulin is converted to insulin by proteolysis and is secreted into the circulation
upon stimulation,the process liberates inactive C-peptide.
The main effect of insulin is to lower blood glucose level as described below
What stimulate insulin secretion?
Carbohydrates as Glucose, Fructose
Hormones as Glucagon and Growth hormone
Some amino Acids, Fatty acids
Glucagon
Produced by the α cells of the islets of Langerhans, it is polypeptide hormone. It is
synthesized from a larger precursor (proglucagon).
It acts through cell membrane receptor.
Its main effect is to elevate blood glucose level.
Stimulators of glucagon secretion
Hypoglycemia, Amino Acids (i.e., Arginine), adrenaline, noradrenaline.
Pancreatic Polypeptide (PP)
PP is peptide hormones. It is synthesized and secreted by F cells (or PP cells). The level
of PP is increased with ingestion of a mixed meal.
27
Somatostatin
It is secreted by δ-cells of the pancreas, is a 14 amino acid peptide, identical to
somatostatin secreted by the hypothalamus.
In neural tissue somatostatin inhibits GH secretion and thus has systemic effects.
In the pancreas, somatostatin acts as a paracrine inhibitor of other pancreatic hormones.
Increasing as blood glucose levels rise and thus leading to down-regulation of glucagon
secretion.
Role of pancreatic hormones
Insulin and glucagon have very important role in the maintenance of blood glucose
within normal range; Glucagon and insulin have antagonistic effects, with glucagon
promoting glucose production and release into the bloodstream, and insulin promoting
the transport of glucose into cells from the bloodstream and inhibiting glucose
production.
i.
in the feeding state
Insulin is the major hormone of the fed state, the ingestion of a meal increases insulin
secretion immediately. The rise in serum insulin is proportional to the rise in serum
glucose, it lower blood glucose by the the following ways:
a) Insulin increases the rate of uptake of glucose into cells by stimulating glucose
transport across the plasma membrane.
b) Insulin reduces the rate of release of glucose from the liver. It does this by:
1) inhibiting glycogenolysis (which is the breakdown of glycogen to glucose)
2) stimulate glycolysis(which is the oxidation of glucose to obtain energy)
3) Enhance glycogen synthesis which is the synthesis of glycogen from glucose.
4) Insulin inhibit gluconeogenesis (gluconeogenesis is the convertion of certain
molecules as amino acid, fatty acid to glucose) by inhibition of fatty acid mobilization
from adipose tissue.
c) Other Insulin effects
In addition to its role in regulating glucose metabolism, insulin is anabolic hormone ,it
stimulates lipogenesis, diminishes lipolysis, and increases amino acid transport into cells.
Insulin also modulates transcription, altering the cell content of mRNAs. It stimulates
growth, DNA synthesis, and cell replication.
ii.
In the Fasting State:
Glucagon, catecholamines and cortisol are the major hormones during fasting state they
are called counterregulatory hormones.
Glucagon from the pancrease raises blood glucose levels by:
28
a) Stimulating the breakdown of glycogen into glucose (glycogenolysis)
b) Stimulating glucose production from amino acids and fatty acids (gluconeogenesis)
c) Glucagon also stimulates ketogenesis, providing an alternative fuel for those tissues that
can use it and sparing glucose for those that cannot act without.
d) Also causes lipolysis in adipose tissue (which provides FFAs and glycerol for
gluconeogenesis).
o Fasting is defined as the condition where the body is deprived of food for at least four
hours. Hypoglycemia is a stressful condition for the body; Glucagon favors use of amino
acids, especially alanine, to produce glucose (gluconeogenesis), and stimulation of
glycogenolysis to increase glucose production. Insulin is decreased in the fasting state, so
the anti-lipolytic effect of insulin is reduced. This, along with some increase in
catecholamines, stimulates breakdown of tissue triglyceride to glycerol and FFA
(lipolysis). Fatty acids are used as energy source.
o Therefore, in the fasting state, in addition to reduction of insulin secretion, three major
hormones which have the opposite effect to that of insulin (and hence are called
counterregulatory hormones) are increased. These hormones are: glucagon,
catecholamines, and cortisol. Growth hormone may also contribute to this mechanism as
a fourth counterregulatory hormone. Fasting, results in reduced insulin and increased
counterregulatory hormones.
hormone resistance syndrome
A condition caused by a reduced or absent end-organ responsiveness to a biologically
active hormone, which may be due to a hormone receptor defect or a post-receptor defect.
Diabetes mellitus
It is a chronic disease of impaired carbohydrate metabolism. β-cells of islets of
Langerhans fail to secrete adequate amounts of insulin (type1 DM)or it may be due to the
resistance to insulin action (type 2DM) or both, this causes hyperglycemia and glycosuria
Secondary changes in the protein, lipid, water & electrolytes metabolism may also occur.
Adipose tissue derived hormones (Adipocytokines)
Adipose tissue is an active metabolic and endocrine organ. it secretes hormones with
important endocrine functions. These include for example leptin, adiponectin and resistin.
Adipose tissue is also a major site for metabolism of sex steroids and
glucocorticoids.example of adipocytes derived hormones:
Leptin
Leptin is a hormone produced by adipocytes.
29
It is involved in the maintenance of a stable body fat mass. Leptin is important in the
regulation of appetite, food intake and energy expenditure, sexual maturation and
fertility, haematopoiesis and activity of the hypothalamic
‐pituitary‐gonadal axis.
Hormones of the Kidney
The human kidney secretes two hormones:
1) Erythropoietin (EPO): is a glycoprotein. It acts on the bone marrow to increase the
production of red blood cells. Stimuli such as bleeding or moving to high altitudes (where
oxygen is less) trigger the release of EPO.
2) Calcitriol acts on the cells of the intestine to promote the absorption of calcium from
food, bone to mobilize calcium from the bone to the blood.
Hormones of the Skin
When ultraviolet radiation strikes the skin, it triggers the conversion of
dehydrocholesterol (a cholesterol derivative) into calciferol (vitamin D
3
). Calciferol
travels in the blood to the liver where it is converted into 25[OH] vitamin D
3
.
This compound travels to the kidneys where it is converted into calcitriol (1,25 [OH]
2
vitamin D
3
). This final step is promoted by the parathyroid hormone (PTH)
Although called a vitamin, calciferol and its products fully qualify as hormones because
they are
o
made in certain cells,
o
carried in the blood,
o
affect gene transcription in target cells.
Hormones of the Heart
Natriuretic Peptides In response to a rise in blood pressure, the heart releases two
peptides:
1) A-type Natriuretic Peptide (ANP) released from stretched atria
2) B-type Natriuretic Peptide (BNP) released from the ventricles.
Both hormones lower blood pressure.