Download Unit One: Introduction to Physiology: The Cell and General

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
Insulin and Its Metabolic Effects
Fig. 78.2
Insulin and Its Metabolic Effects
• Activation of Target Cell Receptors by Insulin
and the Resulting Cellular Effects
Fig. 78.3
Insulin and Its Metabolic Effects
• Activation of Target Cell Receptors by Insulin
and the Resulting Cellular Effects
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
Insulin and Its Metabolic Effects
• Activation of Target Cell Receptors by Insulin
and the Resulting Cellular Effects
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
Insulin and Its Metabolic Effects
• 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
Insulin and Its Metabolic Effects
• Effect of Insulin on Cbh Metabolism
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
Insulin and Its Metabolic Effects
• Effect of Insulin on Cbh Metabolism
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
Insulin and Its Metabolic Effects
• 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
Insulin and Its Metabolic Effects
• Effect of Insulin on Fat Metabolism
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
Insulin and Its Metabolic Effects
• Effect of Insulin on Fat Metabolism
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
Insulin and Its Metabolic Effects
• 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
Insulin and Its Metabolic Effects
• Effect of Insulin on Protein Metabolism
b. Insulin deficiency causes protein depletion and
increased plasma amino acids
c. Insulin and growth hormone interact
synergistically to promote growth
Insulin and Its Metabolic Effects
• Effect of Insulin on Protein Metabolism
Fig. 78.6 Effect of GH, insulin, and GH plus insulin on growth in a depancreatized and hypophysectomized rat
Insulin and Its Metabolic Effects
• Mechanisms of Insulin Secretion
Fig. 78.7 Basic mechanisms of glucose stimulation of insulin secretion
by beta cells of the pancreas
Insulin and Its Metabolic Effects
• 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
Insulin and Its Metabolic Effects
• Control of Insulin Secretion
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
Insulin and Its Metabolic Effects
• Control of Insulin Secretion
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
Glucagon and Its Functions
• 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
Glucagon and Its Functions
• Regulation of Glucagon Secretion
a. Increased blood glucose inhibits glucagon
b. Increased blood amino acids stimulates glucagon
secretion
c. Exercise stimulates glucagon secretion
Glucagon and Its Functions
• Regulation of Glucagon Secretion
Fig. 78.10 Approximate plasma glucagon concentration at different blood glucose levels
Glucagon and Its Functions
• 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)