1. Homeostatic Control of Metabolism

2. Food Intake How does your body know when to eat?
How does your body know how much to eat?
Two ‘competing’ behavioral states:
Appetite = desire for food
Satiety = sense of fullness

3. Hypothalamic Centers Feeding center – tonically active
Satiety center – inhibits feeding center
Figure 11-3

4. Regulation: Classic Theories
Glucostatic theory: glucose levels control the feeding and satiety centers in hypothalamus
Low [glucose] – satiety center suppressed
High [glucose] – satiety center inhibits feeding center
Lipostatic theory: body fat stores regulate the feeding and satiety centers
Low fat levels  increased eating
Recent discovery of leptin and neuropeptide Y provides support

5. Peptides Regulate Feeding
Input to hypothalamus:
Neural from cerebral cortex
Neural from limbic system
Peptide hormones from GI tract
Adipocytokines from adipose tissue

6. Peptides Regulate Feeding
Note the diversity of peptide origins!
cholecystokinin =

7. Peptides Regulate Feeding
inhibition
Figure 22-1

8. We Eat To Do Work Energy input = energy output
Energy output = work + heat
3 categories of work:
Transport work – moving molecules from one side of membrane to the other
Mechanical work – movement
Chemical work – synthesis and storage of molecules
Short-term energy storage – ATP
Long-term energy storage – glycogen, fat

9. Metabolism = sum of all chemical reactions in the body
Anabolic pathways – synthesize large molecules from smaller
Catabolic pathways – break large molecules into smaller

10. Metabolism Divided into two states: Fed (or Absorptive) state
After a meal
Anabolic – energy is stored
Fasted (or Post-absorptive) state
Molecules from meal no longer in bloodstream
Catabolic – storage molecules broken down

11. Fate of Ingested Molecules
Immediate use in energy production: nutrient pools
Synthesis into needed molecules (growth, maintenance)
Storage for later use
Fate depends on type of molecule: carbohydrate, protein, or fat

12. Excess converted in liver Metabolism in most tissues
DIET
Fats
Carbohydrates
Proteins
Build proteins
Free fatty acids + glycerol
Excess stored
Protein synthesis
Glycogenesis
Excess stored
Amino acids
Glucose
Fat stores
Lipogenesis
Excess glucose
Lipogenesis
Glycogen stores
Body protein
Lipolysis
Urine
Glycogenolysis
Glucose pool
Gluconeogenesis
Free fatty acid pool
Range of normal plasma glucose
Amino acid pool
Many immediately used
Excess converted in liver
Many immediately used
Metabolism in most tissues
Brain metabolism
Excess nutrients
Figure 22-2

13. What Controls This?
Hormones control metabolism by altering enzyme activity and molecule movement
Push-pull control: different enzymes catalyze forward and reverse reactions

14. Push-Pull Control INSULIN enzyme 1 enhanced, enzyme 2 inhibited
enzyme 1 inhibited, enzyme 2 enhanced
GLUCAGON
Figure 22-4

15. Metabolism is Controlled by Ratio of Insulin and Glucagon
Anabolic
Catabolic
Figure 22-9

16. Fed State
Many immediately used

17. Fasted State Figure 22-7 1 Liver glycogen becomes glucose. 2
Adipose lipids become free fatty acids and glycerol that enter blood.
Triglyceride stores
Liver glycogen stores
Free fatty acids
Free fatty acids
Glycerol
Glycogenolysis
-oxidation
Gluconeogenesis
Energy production
Ketone bodies
Energy production
Glucose
Glycogen
Proteins
Gluconeogenesis
Pyruvate or
Lactate
Amino acids
Ketone bodies
Glucose
Energy production 3
Muscle glycogen can be used for energy. Muscles also use fatty acids and break down their proteins to amino acids that enter the blood. 4
Brain can use only glucose and ketones for energy.
Figure 22-7

18. Pancreas – Islets of Langerhans
Figure 22-8

19. Insulin Origin in β cells of pancreas Peptide hormone
Transported dissolved in plasma
Half-life ~5 min
Target tissues: liver, muscle, adipose tissue

20. Insulin Secretion promoted by: Secretion inhibited by:
High plasma [glucose] (> 100 mg/dL)
Increased plasma amino acids
Feedforward effects of GI hormones
Glucagon-like peptide-1 (GLP-1)
Gastric inhibitory peptide (GIP)
Anticipatory release of insulin
Parasympathetic input to β cells
Secretion inhibited by:
Sympathetic input
Reduced plasma [glucose]

21. Insulin Mechanism of Action
Extracellular fluid 1
Insulin
Insulin binds to tyrosine kinase receptor. 1 2
Receptor phosphorylates insulin-receptor substrates (IRS). 3
Second messenger pathways alter protein synthesis and existing proteins.
GLUT4 2
IRS
IRS P
Transport activity 4 3 4
Membrane transport is modified.
Second messenger pathways
Nucleus
Enzymes or 5
Cell metabolism is changed. 5
Transcription factors
Changes in metabolism
Figure 22-11

22. Insulin Lowers Plasma Glucose
Increases glucose transport into most insulin-sensitive cells
Enhances cellular utilization and storage of glucose
Enhances utilization of amino acids
Promotes fat synthesis

23. Insulin Increases Glucose Transport
Required for resting skeletal muscle and adipose tissue
Moves GLUT-4 transporters to cell membrane
Exercising skeletal muscle does not require insulin for glucose uptake
In liver cells, indirect influence on glucose transport

24. Insulin Increases Glucose Transport: Skeletal Muscle & Adipose Tissue
GLUT-4 transporters moved to cell membrane
Figure 22-12

25. Insulin Increases Glucose Transport: Indirect in Liver Cells
Insulin activates hexokinase, keeps IC [glucose] low
Figure 22-13

26. Insulin Enhances Utilization and Storage of Glucose
Activates enzymes for:
Glycolysis – glucose utilization
Glycogenesis – glycogen synthesis
Lipogenesis – fat synthesis
Inhibits enzymes for:
Glycogenolysis – glycogen breakdown
Gluconeogenesis – glucose synthesis

27. Insulin Enhances Utilization of Amino Acids
Activates enzymes for protein synthesis in liver and muscle
Inhibits enzymes that promote protein breakdown (no gluconeogenesis)
Excess amino acids converted into fatty acids

28. Insulin Promotes Fat Synthesis
Inhibits β-oxidation of fatty acids
Promotes conversion of excess glucose into triglycerides
Excess triglycerides stored in adipose tissue

29. Energy storage
Glucose metabolism
Figure 22-14

30. Glucagon Origin in α cells of pancreas Peptide hormone
Transported dissolved in plasma
Half-life ~5 min
Target tissues: mostly liver
α cells require insulin to uptake glucose

31. Glucagon Secretion promoted by:
Low plasma [glucose] (< 100 mg/dL)
Increased plasma amino acids
Sympathetic input
Secretion inhibited by increased [glucose]
Inhibition by insulin??

32. Glucagon Raises Plasma Glucose
Main purpose is to respond to hypoglycemia
Activates enzymes for:
Glycogenolysis – glycogen breakdown
Gluconeogenesis – glucose synthesis

33. Response to Hypoglycemia in Fasted State
Figure 22-15

34. Diabetes Mellitus Family of diseases
Chronic elevated plasma glucose levels
= hyperglycemia
Two types:
Type 1 – insulin deficiency
Type 2 – ‘insulin-resistant’ diabetes; cells do not respond to insulin

35. Type 1 Diabetes ~10% of cases
Absorb nutrients normally, but no insulin released – what happens?
Cells shift to fasted state, leading to glucose production!
Results in hyperglycemia and cascading effects

36. Figure 22-16

37. Type 2 Diabetes ~90% of cases
Target cells do not respond normally to insulin
Delayed response to ingested glucose
Leads to hyperglycemia
Often have elevated glucagon – why?
No uptake of glucose by α cells
Release glucagon
Exercise and modified diet help treat – why?