Metabolic Effects of Insulin

1. Metabolic Effects of Insulin on
Cellular Uptake of Glucose
Supachai A. Basit, RMT, PhD

2. Overview
• Four major organs
play a dominant role
in fuel metabolism
• Integration of energy
metabolism is
controlled primarily
by the actions of
insulin and glucagon

3. Insulin
• Polypeptide hormone
produce by the beta cells
of the islet of Langerhans
of the pancreas
• Most important hormone
coordinating the use of
fuels by tissues
• Metabolic effects 
anabolic
– Favoring the synthesis of
glycogen, triacylglycerols
and protein

4. Structure of Insulin
• 51 amino acids
• Polypeptide A and B, linked together by a
disulfide bridges
• Intramolecular disulfide bridge between
amino acid residues of the A chain

5. Synthesis of Insulin
• Two inactive precursors  cleaved to form
the active hormone plus the C-peptide
• C-peptide  essential for proper insulin
folding

7. Stimulation of Insulin Secretion
• Insulin and glucagon
secretion is closely
coordinated at the
islet of Langerhans
• Secretion is
regulated so that the
rate of hepatic
glucose production
is kept equal to the
use of glucose by
peripheral tissues

8. Stimulation of Insulin Secretion is
Increased by: Glucose
• ß cells contain Glut-2
transporters and have
glucokinase activity and thus
can phosphorylate glucose in
amounts proportional to its
actual concentration in blood
• Ingestion of CHO rich meal
leads to a rise in blood
glucose, which is a signal for
insulin secretion and
decrease glucagon synthesis
and release

9. Stimulation of Insulin Secretion is
Increased by: Amino Acids
• Ingestion of protein
causes a transient
rise in plasma amino
acids level, which in
turn induces the
secretion of insulin
• Elevated plasma
arginine stimulates
insulin secretion

10. Stimulation of Insulin Secretion is
Increased by: Gastrointestinal Hormones
• Cholecytoskinin and gastric-
inhibitory peptide increased
insulin secretion
• Incretins
• Released from SI in response
to oral glucose and cause
anticipatory rise in insulin levels
• This may account for the fact
that the same amount of
glucose given orally induces a
much greater secretion of
insulin that is given
intravenously

11. Inhibition of Insulin Secretion: Epinephrine
• Scarcity of dietary fuels and during
the period of stress
• Direct effect on energy metabolism
causing glycogenolysis and
gluconeogenesis
• Can override the normal glucose-
stimulated release of insulin
• In emergency situation, the
sympathetic nervous system
largely replaces the plasma
glucose concentration as the
controlling influence over ß cells
secretion

12. Metabolic Effects of Insulin:
Carbohydrates Metabolism
• Promotes storage in 3
tissues
• In liver & muscle, increase
glycogen synthesis
• In muscle and adipose,
increase glucose uptake
by more GLUT-4
• Insulin decreased the
production of glucose by
inhibiting glycogenolysis
and gluconeogenesis

13. GLUT-4 Transport Protein

14. Metabolic Effects of Insulin:
Lipid Metabolism
Decrease TAG
Degradation
• Insulin inhibits
hormone-sensitive
lipase
• Insulin acts by
promoting the
dephosphorylation and
hence inactivation of
enzymes
Increase TAG Synthesis
• Insulin increases the
transport and metabolism
of glucose into adipocytes
providing substrate for
glycerol-3-phosphate for
TAG synthesis
• Increases the lipoprotein
lipase, thus providing
fatty acids for
esterification

15. Metabolic Effects of Insulin:
Protein Synthesis
• Insulin stimulates
the entry of amino
acids into cells, and
protein synthesis
through activation of
factors required for
translation

16. Insulin binds to specific, high
affinity receptors in the cell
membrane of most tissues
including liver, muscle and
adipose tissue. The following
should be considered
1. Insulin receptor
2. Signal transduction
3. Membrane effects of
insulin
4. Receptor regulation
MechanismofInsulinAction

17. Membrane Effects of Insulin
• Glucose transport increases in the presence of insulin as this
promotes the recruitment of insulin-sensitive glucose transporter
(GLUT-4) from a pool located in intracellular vesicles

18. Characteristics of Glucose Transport in
Various Tissues

19. Receptor Regulation
• Binding of insulin is
followed by internalization
of the hormone-receptor
complex
• Once inside the cell, the
insulin is degraded in the
lysosomes
• The receptors may be
degraded but most are
recycled to the cell
surface