Unit Fourteen: Endocrinology and Reproduction: Chapter 78: Insulin, Glucagon, and Diabetes Mellitus

Unit Fourteen:
Endocrinology and
Reproduction
Chapter 78: Insulin, Glucagon, and
Diabetes Mellitus
Guyton and Hall, Textbook of Medical Physiology, 12 edition

Physiologic Anatomy of the Pancreas
Fig. 78.1 Physiolgic anatomy of an islet of Langerhans in the pancreas

Physiologic Anatomy of the Pancreas
• Pancreas
a. Composed of two major types of tissues, the acini,

which secrete digestive juices, and the islets of
Langerhans, which secrete insulin and glucagon
directly into the blood
b. Alpha cells of the islets-secrete glucagon
c. Beta cells-secrete insulin
d. Delta cells-secrete somatostatin

Insulin and Its Metabolic Effects
• Insulin is a Hormone Associated with Energy

Abundance
a. Composed of two amino acid chains, MW 5808
b. Preproinsulin to a proinsulin to insulin
c. In the blood, it circulates as an unbound form
d. Half-life in circulation is about 6 minutes

Fig. 78.2
• Activation of Target Cell Receptors by Insulin

and the Resulting Cellular Effects
Fig. 78.3

a. Within seconds after insulin binds to its

receptors, 80% of the cells increase their
uptake of glucose (true of muscle and adipose
cells but not the neurons of the brain)
b. Cell membrane becomes more permeable to

many amino acids, potassium ions, and
phosphate ions, causing increased transport of
these substances into the cell

c. Slower effects occur during the next 10-15

minutes to change the activity levels of many
more intracellular metabolic enzymes
d. Much slower effects continue for hours and

even several days; enzymatic functions and
protein synthesis
• Effect of Insulin on Cbh Metabolism
a. Promotes muscle glucose uptake and metabolism;

if the muscle is not exercising, the glucose is stored
as muscle glycogen
b. Promotes liver uptake, storage, an use of glucose
1) Insulin inactivates liver phosphorylase and

prevents the splitting of glycogen into glucose
2) Insulin causes the enhanced uptake of glucose
from the blood by liver cells; increases the
activity of glucokinase
3) Increases the activity of the enzymes that

promote glycogen synthesis
c. Glucose is released from the liver between meals
1) Decreasing blood glucose causes the pancreas

to decrease insulin secretion
2) Lack of insulin reverses the effects of glycogen
storage
3) Lack of insulin activates the splitting of
glycogen into glucose; glucose phosphatase is
activated
d. Insulin promotes the conversion of excess glucose

into fatty acids and inhibits gluconeogenesis in the
liver
e. In the brain most of the cells are permeable to

glucose and can use glucose without the
intermediation of insulin
• Effect of Insulin on Fat Metabolism
a. Promotes fat synthesis and storage
1) Increases the transport of glucose into liver

cells; after the liver glycogen concentration
reaches 5-6%, the glucose becomes available to
form fat (split to acetyl CoA from pyruvate to
make fatty acids)
2) Excesses of citrate and isocitrate are formed
when excess amounts of glucose are being used
for energy—activate enzymes for the first steps
of fatty acid synthesis
a. Promotes fat synthesis and storage
3) Most of the fatty acids are then synthesized

within the liver and used to form triglycerides
b. Role of insulin in the storage of fat in the adipose

cells
1) Insulin inhibits the action of hormone sensitive

lipase
2) Promotes glucose transport through the
membrane into the fat cells
c. Insulin deficiency causes lipolysis of storage fat

and the release of fatty acids
d. Insulin deficiency increases plasma cholesterol and

phospholipid concentrations
e. Excess usage of fats during insulin lack causes

ketosis and acidosis
• Effect of Insulin on Protein Metabolism
a. Insulin promotes protein synthesis and storage of

amino acids
1) Stimulates the transport of many of the aa into

cells
2) Increases the translation of mRNA
3) Increases the rate of transcription of selected
DNA genetic sequences
4) Inhibits the catabolism of proteins
5) In the liver, insulin depresses the rate of
gluconeogenesis
b. Insulin deficiency causes protein depletion and

increased plasma amino acids
c. Insulin and growth hormone interact

synergistically to promote growth
Fig. 78.6 Effect of GH, insulin, and GH plus insulin on growth in a depancreatized and hypophysectomized rat
• Mechanisms of Insulin Secretion
Fig. 78.7 Basic mechanisms of glucose stimulation of insulin secretion

by beta cells of the pancreas
• Control of Insulin Secretion
a. Increased blood glucose stimulates insulin secretion
Fig. 78.8 Increase in plasma insulin concentration after a sudden increase in

blood glucose to 2-3x the normal range
b. Feedback relation between blood glucose

concentration and insulin secretion rate- a rise in
blood glucose increases the secretion of insulin
which in turn increases the transport of glucose into
liver, muscle, and other cells
c. Other factors that stimulate insulin secretion-amino

acids, GI hormones, other hormones, ANS
Fig. 78.9 Approximate insulin secretion at different plasma glucose levels

Glucagon and Its Functions
• Effects on Glucose Metabolism
a. Causes glycogenolysis and increased blood glucose

concentration
1) Glucagon activates adenyl cyclase in the hepatic

cell membrane
2) Which causes the formation of cAMP
3) Which activates protein kinase regulator protein
4) Which activates protein kinase
5) Which activates phosphorylase b kinase
6) Which converts phosphorylase b to a
7) Which promotes the degradation of glycogen into
glucose-1-phosphate
8) Which is dephosphorylated and glucose is released
• Effects on Glucose Metabolism
b. Glucagon increases gluconeogenesis
c. Glucagon activates adipose cell lipase-makes increased

quantities of free fatty acids available
d. Inhibits the storage of triglycerides
e. In high concentrations-enhances the strength of the

heart, increases blood flow in some tissues (kidney),
enhances bile secretion, and inhibits gastric acid
secretion
• Regulation of Glucagon Secretion
a. Increased blood glucose inhibits glucagon
b. Increased blood amino acids stimulates glucagon

secretion
c. Exercise stimulates glucagon secretion

• Regulation of Glucagon Secretion
Fig. 78.10 Approximate plasma glucagon concentration at different blood glucose levels
• Somatostatin Inhibits Glucagon and Insulin Secretion
a. Almost all factors related to the ingestion of food

stimulate somatostatin secretion (increased amino
acids, fatty acids, GI hormones, blood glucose)
b. Acts locally within the islets to decrease secretion of

insulin and glucagon
c. Decreases the motility of the stomach, duoenum, and

gall bladder
d. Decreases secretion and absorption in the GI tract

Diabetes Mellitus
• Diabetes Mellitus
Syndrome of impaired carbohydrate, protein, and

fat metabolism caused by either lack of insulin
secretion or decreased sensitivity of the tissues to
insulin
a. Type I-insulin dependent diabetes mellitus; lack of

insulin secretion
b. Type II-non insulin dependent diabetes mellitus;

initially caused by the decreased sensitivity of tissues
to insulin (insulin resistance)

Unit Fourteen: Endocrinology and Reproduction: Chapter 78: Insulin, Glucagon, and Diabetes Mellitus

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Unit Fourteen:

Guyton and Hall, Textbook of Medical Physiology, 12 edition

Fig. 78.1 Physiolgic anatomy of an islet of Langerhans in the pancreas

a. Composed of two major types of tissues, the acini,

b. Alpha cells of the islets-secrete glucagon

c. Beta cells-secrete insulin

d. Delta cells-secrete somatostatin

• Insulin is a Hormone Associated with Energy

a. Composed of two amino acid chains, MW 5808

b. Preproinsulin to a proinsulin to insulin

c. In the blood, it circulates as an unbound form

d. Half-life in circulation is about 6 minutes

• Activation of Target Cell Receptors by Insulin

• Activation of Target Cell Receptors by Insulin

a. Within seconds after insulin binds to its

b. Cell membrane becomes more permeable to

• Activation of Target Cell Receptors by Insulin

c. Slower effects occur during the next 10-15

d. Much slower effects continue for hours and

• Effect of Insulin on Cbh Metabolism

a. Promotes muscle glucose uptake and metabolism;

b. Promotes liver uptake, storage, an use of glucose

1) Insulin inactivates liver phosphorylase and

3) Increases the activity of the enzymes that

c. Glucose is released from the liver between meals

1) Decreasing blood glucose causes the pancreas

d. Insulin promotes the conversion of excess glucose

e. In the brain most of the cells are permeable to

a. Promotes fat synthesis and storage

1) Increases the transport of glucose into liver

a. Promotes fat synthesis and storage

3) Most of the fatty acids are then synthesized

b. Role of insulin in the storage of fat in the adipose

1) Insulin inhibits the action of hormone sensitive

c. Insulin deficiency causes lipolysis of storage fat

d. Insulin deficiency increases plasma cholesterol and

e. Excess usage of fats during insulin lack causes

a. Insulin promotes protein synthesis and storage of

1) Stimulates the transport of many of the aa into

b. Insulin deficiency causes protein depletion and

c. Insulin and growth hormone interact

• Mechanisms of Insulin Secretion

Fig. 78.7 Basic mechanisms of glucose stimulation of insulin secretion

• Control of Insulin Secretion

a. Increased blood glucose stimulates insulin secretion

Fig. 78.8 Increase in plasma insulin concentration after a sudden increase in

• Control of Insulin Secretion

b. Feedback relation between blood glucose

c. Other factors that stimulate insulin secretion-amino

• Control of Insulin Secretion

Fig. 78.9 Approximate insulin secretion at different plasma glucose levels

a. Causes glycogenolysis and increased blood glucose

1) Glucagon activates adenyl cyclase in the hepatic

b. Glucagon increases gluconeogenesis

c. Glucagon activates adipose cell lipase-makes increased

d. Inhibits the storage of triglycerides

e. In high concentrations-enhances the strength of the

• Regulation of Glucagon Secretion

a. Increased blood glucose inhibits glucagon

b. Increased blood amino acids stimulates glucagon

c. Exercise stimulates glucagon secretion

• Regulation of Glucagon Secretion