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Ch. 14 Part 7
Blood Glucose Regulation
Overview Video
Glucose
• Carbohydrates transported in blood as
soluble molecule called GLUCOSE
– Monosaccharide
– Ring structure in aqueous solution
• Carbohydrates stored as polysaccharide
GLYCOGEN
– Insoluble
– Macromolecule of 1-4 linked alpha glucose
molecules with 1-6 branches
– Easily broken down into glucose
• Main respiratory substrate for many cells
• Healthy adult = 80-120 mg of glucose in
100 mL of blood
Pancreas Overview
• Tissue: Islets of Langerhans
– Groups of cells in pancreas
– Made of 2 types of RECEPTOR
cells that are CENTRAL
CONTROL for homeostasis of
glucose
• Alpha Cells
– Secrete hormone GLUCAGON
• Beta Cells
– Secrete hormone INSULIN
– Hormones of pancreas
coordinate actions of
EFFECTORS
• Liver Cells
• Muscle Cells
• Fat (adipose) cells
Glucagon
• Glucagon is a 29-amino
acid polypeptide
• Regulates the levels of glucose in the
bloodstream
• Produced by the alpha cells of the
islets of Langerhans (pancreas)
• Opposite effect from insulin
– acts to increase blood sugar levels by
stimulating the breakdown of
liver glycogen to glucose (glycogenolysis)
, increasing release of glucose from the
liver into the blood, preventing the liver
from storing glucose, and increasing
glucose formation in the liver from
dietary protein(amino acids) and fats
Insulin
• Signaling molecule
• Two long polypeptide chains
– Chain A with 21 amino acids
– Chain B with 30 amino acids
– Two disulfide bridges covalently connect the
chains
• Helps control blood glucose levels
– signals the liver, muscle and fat cells to take in
glucose from the blood
• Cannot pass through cell membrane
• Binds to transmembrane protein receptor
– Initiates intracellular messengers when it binds
• Many cells have insulin receptors
– Liver, muscle, and fat cells
– Insulin stimulates these cells to increase the
rate at which they absorb glucose, convert it to
glycogen, and use it in respiration
• Causes decrease in concentration of glucose in
blood
After large carb meal….
• Glucose reabsorbed in small intestine into blood
• Blood flows through pancreas
• Alpha and Beta cells detect increase in glucose
concentration
• Alpha cells response:
– Stop the secretion of glucagon
• Beta cells response:
– Secrete insulin into blood plasma
• Blood carries insulin to all parts of the body
What does Insulin do?
Attaches to insulin receptors on cell membranes
and:
1. Activate GLUT transporter protein containing
vesicles to fuse with cell membrane
2. Stimulates the activation of enzymes:
•
•
•
GLUKOKINASE
PHOSPHOFRUCTOKINASE
GLYCOGEN SYNTHASE
How Glucose Enters Cells
• Glucose must enter cells
through transporter proteins
called GLUTs
– GLUT 1: brain cells
• Regulated by blood glucose levels
– GLUT 2: liver cells
• Always in cell membrane
– GLUT 4: muscle cells
• Regulated by blood glucose levels
• GLUT proteins in vesicles kept
in cytoplasm (like aquaporins)
– Move to and fuse with cell
membrane when insulin
attaches to transmembrane
receptor
– Some GLUT transporters are
always in membrane
VIDEO
Enzyme Activation
• GLUCOKINASE
– Phosphorylates glucose
• Keeps glucose in the cell
(phosphorylated glucose cannot
pass through transporter proteins)
• PHOSPHOFRUCTOKINASE
– converts fructose 6-phosphate
and ATP to fructose 1,6bisphosphate and ADP in
glycolysis
– Helps add glucose to glycogen
with the help of glycogen
synthase
• GLYCOGEN SYNTHASE
– Converts glucose to glycogen
Decrease in Blood Glucose Concentration…
• Alpha and beta cells detect decease
– Alpha cells secrete glucagon
– Beta cells stop secreting insulin
• Reduce rate of glucose UPTAKE and
glucose USE by liver and muscle cells
– Uptake continues but at slower rate
• Glucagon binds to receptors in cell
surface membrane of liver cells
– Activates signal transduction pathway
• Glucose also made and added to blood
by GLUCONEOGENESIS
• Due to release of glucagonLiver
releases extra glucose to INCREASE
blood glucose concentration
– Muscle cells do NOT have receptors for
glucagon so they do NOT resond to
glucagon
Glucagon Signal Transduction Pathway
• Glucagon binds to receptor in membrane
• Conformational changes to transmembrane
protein occur leading to ACTIVATION of G
protein inside side (GDPGTP)
• G protein activates cell-membrane enzyme
that catalyzes conversion of ATP to cyclic
AMP (cAMP) “second messenger”
• cAMP binds to kinase enzymes in cytoplasm
that activate other enzymes
• Final enzyme to be activated: GLYCOGEN
PHOSPHORYLASE
– Catalyzes the breakdown of GLYCOGEN to
GLUCOSE = increase in concentration of glucose
inside cell = glucose diffuses OUT of cell and into
blood through GLUT2 transporter
“Enzyme Cascade
Amplification”
GLUCONEOGENESIS
• “formation of
glucose”
• Amino acids and
lipids used to make
glucose
• Hormone
• Increases concentration of
blood glucose
• Binds to different receptors in
surface of liver cells
– Activate same enzyme
cascade
– Same result: glycogen
phosphorylase breaks down
glycogen into glucose
• Stimulates breakdown of
glycogen in muscle cells during
exercise
– Glucose released directly into
muscle cell where it is needed
• Glucagon and insulin work
together
• Negative feedback system
• Receptors activated by any
deviation of blood glucose
concentration from set point
• Effectors will bring blood
glucose concentration back to
set point
• Blood glucose concentrations
never constant
– Time delay in change of blood
glucose concentration and
onset of actions to correct it
– Time delays = oscillations in
set point
Diabetes Mellitus
• “Sugar” diabetes
• 2013- 382 million people (8.3%)
• Two Types
– Insulin-dependent diabetes (Type 1)
– Non-insulin dependent diabetes (Type 2)
• Symptoms
– Blood glucose concentration increases (after a meal)
• Normal conditions: no glucose in urine
• High blood glucose concentration: kidney not able to reabsorb all glucose = glucose in urine
– Excess water and salts also not reabsorbed dehydration and hunger
– Slow uptake of glucose from blood into cells
– Cells lack glucose-> metabolize fats and proteins  build up of keto-acids in blood =
decrease in blood pH
– Extreme conditions:
• Dehydration
• Salt loss
• Low blood pH
– Between meals: blood glucose concentration drops drastically
• No glycogen to breakdown
• May result in coma
Insulin-dependent diabetes (Type 1)
•
Pancreas incapable of secreting sufficient insulin
–
–
•
•
“Juvenile” onset diabetes
Regular insulin injections
–
•
•
Deficiency in gene that codes for insulin production
Attack on beta cells by immune system
Insulin made by genetically engineered cells
Take blood samples to monitor effectiveness of
insulin
Controlled diet to maintain near constant levels of
glucose
Non-insulin dependent diabetes
(Type 2)
• Pancreas DOES produce insulin
– Liver and muscle cells do NOT
respond properly to insulin
• Late onset (adult)
• Associated with obesity and
diet
• Rarely need insulin injections
• Healthy diet
• Frequent excecise