Transcript GlucoseHomeostasis2

Plasma Glucose Homeostasis
Widmaier et al., p. 555-567
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Glucose metabolism
Hormonal Control
Disruptions of glucose homeostasis
A Case Study
1QQ # 3 8:30 Section
1. Which of the following are true during the absorptive
phase? (Circle all correct responses.)
a) Amino acids are taken up by muscle tissue.
b) The liver converts glucose to a-ketoacids.
c) Muscle cells polymerize glucose to glycogen.
d) Excess amino acids are converted to triglycerides in
the liver in a multi-stop enzymatic process
e) As plasma glucose levels rise, so does the secretion
of insulin.
f) Adipose tissue converts excess glucose to
triglycerides.
g) Almost all cells use glucose as metabolic fuel.
1 a b c d e
f
g
1QQ # 3 9:30 Section
1. Which of the following are true during the absorptive
phase? (Circle all correct responses.)
a) Amino acids are released by muscle tissue.
b) The liver converts glucose to a-ketoacids.
c) Muscle cells polymerize glucose to glycogen.
d) Excess amino acids are converted to triglycerides in
the liver in a multi-stop enzymatic process
e) As plasma glucose levels rise, secretion of insulin is
diminished.
f) Triglycerides enter adipose tissue cells.
g) Almost all cells use fatty acids as their main
metabolic fuel.
1 a b c d e
f
g
Absorptive
Phase
Fig. 16.01
Lipoprotein Lipase
=sink
Hepatic Portal System
Liver
Typical vasculature: Artery-Arteriole-Capillary-Venule-Vein-Heart
Islets of Langerhans
Alpha cells secrete glucagon
Beta cells secrete insulin
Delta cells secrete somatostatin
Route of blood
Hepatic portal system
Artery-Arteriole-Capillary-Portal Vessel- Capillary-Venule-Vein-Heart
Fig. 16.02
Special case:
Muscle
wasting of
starvation
Glucose
Sparing
Special term:
Glycogenolysis &
Gluconeogenesis
Post-absorptive
phase
Note: Nervous tissue
can use glucose and
ketones
Major Points
• Absorptive phase lasts ~ 4 hours, cells “burn” glucose.
• During absorptive phase, energy needs provided by
recently digested food
• During absorptive phase, excess is converted to
stored fuel
• During post-absorptive phase, energy need met by
release of stored fuels, most cells “burn” fatty acids,
nervous tissue uses glucose and ketones.
• Fasting defined as greater than 12 hours after
previous meal (some say 24 hrs)
• Fasting for several days has little effect on plasma
glucose levels
The Issues
• How do cells “know” which fuel to “burn?”
• How do cells “know” when to synthesize
glycogen or lipids and when to break down
glycogen or lipid?
• What is responsible for the transitions from
the absorptive and post-absorptive states?
• How does glucose get into “sink” cells?
Identify sensors,
afferent pathway,
integrator,
efferent pathway,
effectors
Fig. 16.07
How is insulin secretion
affected if plasma
glucose is lower than
set point?
Which cell types have
insulin receptors?
Exercise (via an undescribed mechanism)
increases the number of glucose
transporters in muscle cell membrane
Peptide hormone
GLUT-4
Activates some enzymes, inactivates others
↑ plasma glucose →↑insulin secretion→↑glucose uptake into cells →↓ plasma glucose
Diabetes mellitus:
T1DM =beta cells fail to produce adequate insulin (5%)
T2DM = target cells “resistant” (less responsive) to insulin
Stimulatory
actions of
insulin in
green
Inhibitory
actions of
insulin in
dashed red
Absorptive Phase
Post-Absorptive Phase
Thinking
about food
Factors that influence Insulin Secretion
?
FF
WHY?
The Integrator
integrates multiple
inputs
FF
Glucose
uptake,
Storage,
Lipogenesis
Another
hormone that
regulates
plasma glucose
concentration
Glucagon prevails
during postabsorptive phase
Transition from
absorptive to postabsorptive phase?
Graph your daily caloric intake
over a 48 hour period
Plasma
Glucose
Calories
consumed
100
65
6am
Noon
6pm
MN
6am
Noon
6pm
MN
6am
Overlay INSULIN SECRETION on the graph
Overlay GLUCAGON SECRETION on the graph
Noon
Glucose-counterregulatory
controls
(oppose effects of insulin)
Glucagon
Epinephrine
Cortisol (permissive effect)
Growth hormone (permissive effect)
Fig. 16.10
EPI, yet another horomone in
glucose homeostasis, effects
opposite of Insulin
Don’t fret about
receptors, afferent
pathway, and
integrator for this
feedback loop.
Who
Cares?
A Case Study
• On our website at
• http://webs.wofford.edu/davisgr/bio342/oggt.htm
A Case Study of Glucose Homeostasis
A 35 year old male presented with the following complaints: frequent severe
headaches upon awakening at 4:30 am, blurred vision, and fatigue due to excessive
stress at work. The patient complained of routine 16 hr workdays followed by a
midnight snack of breakfast cereal.
An OGTT was ordered and provided the following results:
During the second hour of the OGTT, the patient exhibited anxiety, paleness, hunger,
tremulousness, and cold sweat. No additional tests were ordered. The patient was
instructed to replace the midnight snack of cereal with a protein-rich snack.
Oral Glucose Tolerance Test
• Overnight fast, no
beverages other than water
• Fasting blood sample
• Ingest 75 grams glucose
• Blood samples every 0.5
hours for 3-5 hours
• Plot plasma glucose
concentration over time
• Compare curves
Sugar content
of Red Bull?
60
Stress,
Emergency
(fight or flight)
Effect on
Alpha Cells
Effect on
Beta cells
The Answer to the Problem?
• Rationale for substituting protein
for carbohydrate midnight snack?