HORMONES OF THE PANCREAS
Introduction
The pancreas is a composite organ, which has exocrine and endocrine
functions. The endocrine portion is arranged as discrete islets of
Langerhans, which are composed of five different endocrine cell types
(alpha, beta, delta, epsilon, and upsilon) secreting at least five hormones
including glucagon, insulin, somatostatin, ghrelin, and pancreatic
polypeptide, respectively.
Pancreatic Hormones and Their Function
Insulin
Source: Beta cells of islets of the pancreas.
Synthesis: Insulin is a peptide hormone. The insulin mRNA is translated
as a single-chain precursor called preproinsulin, and removal of its
signal peptide during insertion into the endoplasmic reticulum generates
proinsulin. Within the endoplasmic reticulum, proinsulin is exposed to
several specific endopeptidases, which excise the C peptide (one of three
domains of proinsulin), thereby generating the mature form of insulin.
Insulin is secreted from the cell by exocytosis and diffuses into islet
capillary blood. C-peptide is also secreted into the blood in a 1:1 molar
ratio with insulin. Although C-peptide has no established biological
action, it is used as a useful marker for insulin secretion.
Transport: insulin circulates entirely in unbound form (T1/2 = 6 min).
Main Target cells: hepatic, muscle and adipocyte cells (i.e., cells
specialized for energy storage).
Mechanism of action: Insulin binds to a specific receptor tyrosine kinase
on the plasma membrane and increases its activity to phosphorylate
numerous regulatory enzymes and other protein substrates.
Regulation of its secretion:
, Plasma glucose level is the main regulator of insulin secretion. The
change in the concentration of plasma glucose that occurs in response to
feeding or fasting is the main determinant of insulin secretion. Modest
increases in plasma glucose level provoke a marked increase in plasma
insulin concentration. Glucose is taken up by beta cells via glucose
transporters (GLUT2). The subsequent metabolism of glucose increases
cellular adenosine triphosphate (ATP) concentrations and closes ATP-
dependent potassium (KATP) channels in the beta cell membrane,
causing membrane depolarization and an influx of calcium. Increased
calcium intracellular concentration results in an increase of insulin
secretion.
Increased plasma amino acid and free fatty acid concentrations induce
insulin secretion as well.
Glucagon is also known to be a strong insulin secretagogue.
Physiological functions:
Insulin plays an important role to keep plasma glucose value within a
relatively narrow range throughout the day (glucose homeostasis).
Insulin’s main actions are (1) In the liver, insulin promotes glycolysis
and storage of glucose as glycogen (glycogenesis), as well as conversion
of glucose to triglycerides, (2) In muscle, insulin promotes the uptake of
glucose and its storage as glycogen, and (3) in adipose tissue, insulin
promotes uptake of glucose and its conversion to triglycerides for
storage.
Amylin (diabetes-associated peptide)
Source: Beta cells of islets of the pancreas. It is co-secreted with insulin
in response to caloric intake (feeding state).
Target cells: Alpha cells of islets of pancreas and hypothalamus.
Physiological functions: it suppresses glucagon secretion from the alpha
cells of the islets in the pancreas via paracrine interaction between beta
Introduction
The pancreas is a composite organ, which has exocrine and endocrine
functions. The endocrine portion is arranged as discrete islets of
Langerhans, which are composed of five different endocrine cell types
(alpha, beta, delta, epsilon, and upsilon) secreting at least five hormones
including glucagon, insulin, somatostatin, ghrelin, and pancreatic
polypeptide, respectively.
Pancreatic Hormones and Their Function
Insulin
Source: Beta cells of islets of the pancreas.
Synthesis: Insulin is a peptide hormone. The insulin mRNA is translated
as a single-chain precursor called preproinsulin, and removal of its
signal peptide during insertion into the endoplasmic reticulum generates
proinsulin. Within the endoplasmic reticulum, proinsulin is exposed to
several specific endopeptidases, which excise the C peptide (one of three
domains of proinsulin), thereby generating the mature form of insulin.
Insulin is secreted from the cell by exocytosis and diffuses into islet
capillary blood. C-peptide is also secreted into the blood in a 1:1 molar
ratio with insulin. Although C-peptide has no established biological
action, it is used as a useful marker for insulin secretion.
Transport: insulin circulates entirely in unbound form (T1/2 = 6 min).
Main Target cells: hepatic, muscle and adipocyte cells (i.e., cells
specialized for energy storage).
Mechanism of action: Insulin binds to a specific receptor tyrosine kinase
on the plasma membrane and increases its activity to phosphorylate
numerous regulatory enzymes and other protein substrates.
Regulation of its secretion:
, Plasma glucose level is the main regulator of insulin secretion. The
change in the concentration of plasma glucose that occurs in response to
feeding or fasting is the main determinant of insulin secretion. Modest
increases in plasma glucose level provoke a marked increase in plasma
insulin concentration. Glucose is taken up by beta cells via glucose
transporters (GLUT2). The subsequent metabolism of glucose increases
cellular adenosine triphosphate (ATP) concentrations and closes ATP-
dependent potassium (KATP) channels in the beta cell membrane,
causing membrane depolarization and an influx of calcium. Increased
calcium intracellular concentration results in an increase of insulin
secretion.
Increased plasma amino acid and free fatty acid concentrations induce
insulin secretion as well.
Glucagon is also known to be a strong insulin secretagogue.
Physiological functions:
Insulin plays an important role to keep plasma glucose value within a
relatively narrow range throughout the day (glucose homeostasis).
Insulin’s main actions are (1) In the liver, insulin promotes glycolysis
and storage of glucose as glycogen (glycogenesis), as well as conversion
of glucose to triglycerides, (2) In muscle, insulin promotes the uptake of
glucose and its storage as glycogen, and (3) in adipose tissue, insulin
promotes uptake of glucose and its conversion to triglycerides for
storage.
Amylin (diabetes-associated peptide)
Source: Beta cells of islets of the pancreas. It is co-secreted with insulin
in response to caloric intake (feeding state).
Target cells: Alpha cells of islets of pancreas and hypothalamus.
Physiological functions: it suppresses glucagon secretion from the alpha
cells of the islets in the pancreas via paracrine interaction between beta
