PHYSIOLOGY
Hall, J. E. (2016). Guyton and Hall Textbook of Medical Physiology (13th ed.). Elsevier.
Insulin, Glucagon, and Diabetes Mellitus
• The pancreas has both digestive and hormonal INSULIN AND ITS METABOLIC EFFECTS
functions. It releases two key hormones, insulin and • Insulin was first discovered in 1922 by Banting and
glucagon, which help regulate the metabolism of Best, changing the lives of patients with severe
glucose, fats (lipids), and proteins. diabetes from a rapid decline to near-normal health.
• The pancreas also produces other hormones like • Insulin is widely known for its role in regulating blood
amylin, somatostatin, and pancreatic polypeptide, sugar (glucose), but it also affects fat (lipid)
but their roles are not as well understood. metabolism and protein metabolism.
• This chapter focuses on the functions of insulin and • In diabetes, abnormal fat metabolism can lead to
glucagon and how their abnormal secretion or activity acidosis and arteriosclerosis, which contribute to
can lead to diseases like diabetes mellitus. serious health problems.
• If diabetes remains untreated for a long time, the body
PHYSIOLOGY ANATOMY OF THE PANCREAS loses its ability to build proteins, leading to tissue
wasting and other cell dysfunctions.
The pancreas consists of two main types of tissues (see o This shows that insulin plays a key role in fat and
Figure 79-1): protein metabolism, just as much as it does in
1. Acini – These produce digestive enzymes that are carbohydrate metabolism.
released into the duodenum. (Digestive functions
are covered in Chapter 65.) INSULIN IS A HORMONE ASSOCIATED WITH ENERGY
2. Islets of Langerhans – These clusters of cells
ABUNDANCE
release insulin and glucagon directly into the
bloodstream. • Insulin secretion is linked to energy abundance. When
There are 1 to 2 million islets of Langerhans in the a person eats a diet rich in carbohydrates, insulin levels
human pancreas, each about 0.3 millimeters in size. rise.
The islets contain small capillaries into which their • Insulin helps store excess energy by converting
cells secrete hormones. They are made up of three carbohydrates into glycogen, mainly in the liver and
major cell types:
muscles.
• Beta cells (60%) –
o If glycogen storage is full, insulin promotes the
Found mostly in
the center of the conversion of excess carbohydrates into fat, which
islets, they is stored in adipose tissue.
produce insulin • Insulin also helps in protein metabolism by promoting
and amylin the uptake of amino acids into cells, encouraging their
(though amylin’s conversion into proteins while preventing protein
function is not well
breakdown.
understood).
• Alpha cells (25%) – They release glucagon.
INSULIN CHEMISTRY AND SYNTHESIS
• Delta cells (10%) – They produce somatostatin.
• Insulin is a small protein with
• PP cells – Present in small amounts, they secrete
pancreatic polypeptide, whose function is a molecular weight of 5808.
unclear. It consists of two amino acid
The different cell types in the islets of Langerhans chains linked by disulfide
interact closely and regulate each other’s hormone bonds (see Figure 79-2). If
secretion. For example: these chains are split, insulin
• Insulin inhibits glucagon release. loses its function.
• Amylin inhibits insulin secretion.
• In the beta cells of the
• Somatostatin suppresses both insulin and
glucagon secretion. pancreas, insulin is produced
This coordination helps maintain balanced hormone through normal protein
levels in the body. synthesis (explained in
Chapter 3).
Prepared by: Yam Flynge Ferrer
Email:
, • The process begins with preproinsulin, which has a • When insulin binds to the alpha subunits, the beta
molecular weight of 11,500. subunits inside the cell undergo autophosphorylation
• This is converted into proinsulin (molecular weight (they attach phosphate groups to themselves).
9000), which consists of three peptide chains: A, B, o This activates a tyrosine kinase enzyme, which
and C. Most proinsulin is further processed in the Golgi then phosphorylates other intracellular
apparatus to form insulin (made of A and B chains enzymes, including a group called insulin-
linked by disulfide bonds) and C peptide (connecting receptor substrates (IRS). Different types of IRS
peptide). Both are packaged in secretory granules and proteins (such as IRS-1, IRS-2, and IRS-3) are
released in equal amounts. About 5-10% of the found in different tissues. Some enzymes are
secreted product remains as proinsulin. activated, while others are inhibited, allowing
• While proinsulin and C peptide have little to no insulin insulin to regulate carbohydrate, fat, and protein
activity, C peptide binds to a G protein–coupled metabolism.
receptor, activating enzymes like sodium-potassium
THE MAIN EFFECTS OF INSULIN STIMULATION ARE:
ATPase and endothelial nitric oxide synthase. The
1. Rapid Glucose Uptake (Within Seconds)
exact role of C peptide in these processes is still
o About 80% of body cells quickly increase their
unclear.
glucose uptake after insulin binds.
• Measuring C peptide levels using radioimmunoassay
o This effect is strongest in muscle cells and
can help assess natural insulin production in diabetic
adipose (fat) cells but does not apply to most
patients. Patients with type 1 diabetes, who cannot
neurons in the brain.
produce insulin, typically have very low C peptide
o Inside the cell, glucose is phosphorylated and
levels.
used in normal carbohydrate metabolism.
• Once insulin enters the bloodstream, it remains mostly
o The increased glucose transport happens
unbound and has a plasma half-life of about 6
because intracellular vesicles carrying glucose
minutes. It is cleared within 10 to 15 minutes, mainly
transport proteins move to the cell membrane,
by the liver, with smaller amounts broken down in the
allowing glucose to enter.
kidneys, muscles, and other tissues. The enzyme
o When insulin levels drop, these vesicles detach
insulinase is responsible for its breakdown.
from the membrane and return inside the cell
o Rapid removal of insulin from the blood is essential
within 3 to 5 minutes, ready for reuse.
because stopping its effects is just as important as
2. Increased Permeability to Other Substances
starting them at the right time.
o Insulin makes the cell membrane more
ACTIVATION OF TARGET CELL RECEPTORS BY INSULIN permeable to amino acids, potassium ions,
AND THE RESULTING CELLULAR EFFECTS and phosphate ions, allowing more of these
• For insulin to affect target substances to enter the cell.
cells, it must first bind to 3. Metabolic Enzyme Activation (Within 10-15
and activate a membrane Minutes)
receptor protein with a o Insulin changes the activity of intracellular
molecular weight of about enzymes by altering their phosphorylation
300,000 (see Figure 79-3). states.
The activated receptor 4. Long-Term Effects on Protein Synthesis (Over
then triggers the effects of Hours to Days)
insulin inside the cell. o Over time, insulin influences gene expression
• The insulin receptor by:
consists of four subunits § Increasing translation of messenger RNA
held together by disulfide (mRNA) at the ribosomes, leading to new
bonds: protein formation.
o Two alpha subunits – Located outside the cell § Altering transcription of DNA in the cell
membrane, where insulin binds. nucleus, modifying the cell’s enzymatic
o Two beta subunits – These pass through the machinery.
membrane and extend into the cell cytoplasm.
Prepared by: Yam Flynge Ferrer
Email:
Hall, J. E. (2016). Guyton and Hall Textbook of Medical Physiology (13th ed.). Elsevier.
Insulin, Glucagon, and Diabetes Mellitus
• The pancreas has both digestive and hormonal INSULIN AND ITS METABOLIC EFFECTS
functions. It releases two key hormones, insulin and • Insulin was first discovered in 1922 by Banting and
glucagon, which help regulate the metabolism of Best, changing the lives of patients with severe
glucose, fats (lipids), and proteins. diabetes from a rapid decline to near-normal health.
• The pancreas also produces other hormones like • Insulin is widely known for its role in regulating blood
amylin, somatostatin, and pancreatic polypeptide, sugar (glucose), but it also affects fat (lipid)
but their roles are not as well understood. metabolism and protein metabolism.
• This chapter focuses on the functions of insulin and • In diabetes, abnormal fat metabolism can lead to
glucagon and how their abnormal secretion or activity acidosis and arteriosclerosis, which contribute to
can lead to diseases like diabetes mellitus. serious health problems.
• If diabetes remains untreated for a long time, the body
PHYSIOLOGY ANATOMY OF THE PANCREAS loses its ability to build proteins, leading to tissue
wasting and other cell dysfunctions.
The pancreas consists of two main types of tissues (see o This shows that insulin plays a key role in fat and
Figure 79-1): protein metabolism, just as much as it does in
1. Acini – These produce digestive enzymes that are carbohydrate metabolism.
released into the duodenum. (Digestive functions
are covered in Chapter 65.) INSULIN IS A HORMONE ASSOCIATED WITH ENERGY
2. Islets of Langerhans – These clusters of cells
ABUNDANCE
release insulin and glucagon directly into the
bloodstream. • Insulin secretion is linked to energy abundance. When
There are 1 to 2 million islets of Langerhans in the a person eats a diet rich in carbohydrates, insulin levels
human pancreas, each about 0.3 millimeters in size. rise.
The islets contain small capillaries into which their • Insulin helps store excess energy by converting
cells secrete hormones. They are made up of three carbohydrates into glycogen, mainly in the liver and
major cell types:
muscles.
• Beta cells (60%) –
o If glycogen storage is full, insulin promotes the
Found mostly in
the center of the conversion of excess carbohydrates into fat, which
islets, they is stored in adipose tissue.
produce insulin • Insulin also helps in protein metabolism by promoting
and amylin the uptake of amino acids into cells, encouraging their
(though amylin’s conversion into proteins while preventing protein
function is not well
breakdown.
understood).
• Alpha cells (25%) – They release glucagon.
INSULIN CHEMISTRY AND SYNTHESIS
• Delta cells (10%) – They produce somatostatin.
• Insulin is a small protein with
• PP cells – Present in small amounts, they secrete
pancreatic polypeptide, whose function is a molecular weight of 5808.
unclear. It consists of two amino acid
The different cell types in the islets of Langerhans chains linked by disulfide
interact closely and regulate each other’s hormone bonds (see Figure 79-2). If
secretion. For example: these chains are split, insulin
• Insulin inhibits glucagon release. loses its function.
• Amylin inhibits insulin secretion.
• In the beta cells of the
• Somatostatin suppresses both insulin and
glucagon secretion. pancreas, insulin is produced
This coordination helps maintain balanced hormone through normal protein
levels in the body. synthesis (explained in
Chapter 3).
Prepared by: Yam Flynge Ferrer
Email:
, • The process begins with preproinsulin, which has a • When insulin binds to the alpha subunits, the beta
molecular weight of 11,500. subunits inside the cell undergo autophosphorylation
• This is converted into proinsulin (molecular weight (they attach phosphate groups to themselves).
9000), which consists of three peptide chains: A, B, o This activates a tyrosine kinase enzyme, which
and C. Most proinsulin is further processed in the Golgi then phosphorylates other intracellular
apparatus to form insulin (made of A and B chains enzymes, including a group called insulin-
linked by disulfide bonds) and C peptide (connecting receptor substrates (IRS). Different types of IRS
peptide). Both are packaged in secretory granules and proteins (such as IRS-1, IRS-2, and IRS-3) are
released in equal amounts. About 5-10% of the found in different tissues. Some enzymes are
secreted product remains as proinsulin. activated, while others are inhibited, allowing
• While proinsulin and C peptide have little to no insulin insulin to regulate carbohydrate, fat, and protein
activity, C peptide binds to a G protein–coupled metabolism.
receptor, activating enzymes like sodium-potassium
THE MAIN EFFECTS OF INSULIN STIMULATION ARE:
ATPase and endothelial nitric oxide synthase. The
1. Rapid Glucose Uptake (Within Seconds)
exact role of C peptide in these processes is still
o About 80% of body cells quickly increase their
unclear.
glucose uptake after insulin binds.
• Measuring C peptide levels using radioimmunoassay
o This effect is strongest in muscle cells and
can help assess natural insulin production in diabetic
adipose (fat) cells but does not apply to most
patients. Patients with type 1 diabetes, who cannot
neurons in the brain.
produce insulin, typically have very low C peptide
o Inside the cell, glucose is phosphorylated and
levels.
used in normal carbohydrate metabolism.
• Once insulin enters the bloodstream, it remains mostly
o The increased glucose transport happens
unbound and has a plasma half-life of about 6
because intracellular vesicles carrying glucose
minutes. It is cleared within 10 to 15 minutes, mainly
transport proteins move to the cell membrane,
by the liver, with smaller amounts broken down in the
allowing glucose to enter.
kidneys, muscles, and other tissues. The enzyme
o When insulin levels drop, these vesicles detach
insulinase is responsible for its breakdown.
from the membrane and return inside the cell
o Rapid removal of insulin from the blood is essential
within 3 to 5 minutes, ready for reuse.
because stopping its effects is just as important as
2. Increased Permeability to Other Substances
starting them at the right time.
o Insulin makes the cell membrane more
ACTIVATION OF TARGET CELL RECEPTORS BY INSULIN permeable to amino acids, potassium ions,
AND THE RESULTING CELLULAR EFFECTS and phosphate ions, allowing more of these
• For insulin to affect target substances to enter the cell.
cells, it must first bind to 3. Metabolic Enzyme Activation (Within 10-15
and activate a membrane Minutes)
receptor protein with a o Insulin changes the activity of intracellular
molecular weight of about enzymes by altering their phosphorylation
300,000 (see Figure 79-3). states.
The activated receptor 4. Long-Term Effects on Protein Synthesis (Over
then triggers the effects of Hours to Days)
insulin inside the cell. o Over time, insulin influences gene expression
• The insulin receptor by:
consists of four subunits § Increasing translation of messenger RNA
held together by disulfide (mRNA) at the ribosomes, leading to new
bonds: protein formation.
o Two alpha subunits – Located outside the cell § Altering transcription of DNA in the cell
membrane, where insulin binds. nucleus, modifying the cell’s enzymatic
o Two beta subunits – These pass through the machinery.
membrane and extend into the cell cytoplasm.
Prepared by: Yam Flynge Ferrer
Email:
