1. Plasma Glucose Homeostasis Widmaier et al., p. 555-567
Glucose metabolism
Hormonal Control
Disruptions of glucose homeostasis
A Case Study

2. 1QQ # 3 8:30 Section
Which of the following are true during the absorptive phase? (Circle all correct responses.)
Amino acids are taken up by muscle tissue.
The liver converts glucose to a-ketoacids.
Muscle cells polymerize glucose to glycogen.
Excess amino acids are converted to triglycerides in the liver in a multi-stop enzymatic process
As plasma glucose levels rise, so does the secretion of insulin.
Adipose tissue converts excess glucose to triglycerides.
Almost all cells use glucose as metabolic fuel.
1 a b c d e f g

3. 1QQ # 3 9:30 Section
Which of the following are true during the absorptive phase? (Circle all correct responses.)
Amino acids are released by muscle tissue.
The liver converts glucose to a-ketoacids.
Muscle cells polymerize glucose to glycogen.
Excess amino acids are converted to triglycerides in the liver in a multi-stop enzymatic process
As plasma glucose levels rise, secretion of insulin is diminished.
Triglycerides enter adipose tissue cells.
Almost all cells use fatty acids as their main metabolic fuel.
1 a b c d e f g

4. Absorptive Phase Fig. 16.01 =sink Hepatic Portal System
Lipoprotein Lipase
Absorptive Phase
16.01.jpg
Hepatic Portal System

5. Liver Hepatic portal system Alpha cells secrete glucagon
Typical vasculature: Artery-Arteriole-Capillary-Venule-Vein-Heart
Islets of Langerhans
Alpha cells secrete glucagon
Beta cells secrete insulin
Delta cells secrete somatostatin
Hepatic portal system
Artery-Arteriole-Capillary-Portal Vessel- Capillary-Venule-Vein-Heart
Route of blood

6. Post-absorptive phase
Fig
Special case: Muscle wasting of starvation
Glucose Sparing
Special term:
Glycogenolysis & Gluconeogenesis
16.02.jpg
Post-absorptive phase
Note: Nervous tissue can use glucose and ketones

7. 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

8. 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?

9. Which cell types have insulin receptors?
Fig
Identify sensors, afferent pathway, integrator, efferent pathway, effectors
How is insulin secretion affected if plasma glucose is lower than set point?
16.07.jpg
Which cell types have insulin receptors?

10. T1DM =beta cells fail to produce adequate insulin (5%)
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

11. Stimulatory actions of insulin in green
Inhibitory actions of insulin in dashed red

12. Post-Absorptive Phase
16.04.jpg
Post-Absorptive Phase

13. ? FF FF Glucose uptake, Storage, Lipogenesis
Thinking about food
Factors that influence Insulin Secretion ? FF FF
WHY?
16.08.jpg
Glucose uptake, Storage, Lipogenesis
The Integrator integrates multiple inputs

14. Another hormone that regulates plasma glucose concentration
Glucagon prevails during post-absorptive phase
16.09.jpg
Transition from absorptive to post-absorptive phase?

15. Graph your daily caloric intake over a 48 hour period
Plasma Glucose
100 65
consumed
Calories
6am
Noon
6pm MN
6am
Noon
6pm MN
6am
Noon
Overlay INSULIN SECRETION on the graph
Overlay GLUCAGON SECRETION on the graph

16. Glucose-counterregulatory controls (oppose effects of insulin)
Glucagon
Epinephrine
Cortisol (permissive effect)
Growth hormone (permissive effect)

17. Fig
Don’t fret about receptors, afferent pathway, and integrator for this feedback loop.
EPI, yet another horomone in glucose homeostasis, effects opposite of Insulin
16.10.jpg

18. Who Cares?

19. A Case Study On our website at
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.

20. 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?

21. Hypoglycemia 60

22. Stress, Emergency (fight or flight)
Effect on Alpha Cells
Effect on
Beta cells

23. The Answer to the Problem?
Rationale for substituting protein for carbohydrate midnight snack?