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Homeostatic Control of Metabolism. 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. Hypothalamic Centers. Feeding center – tonically active - PowerPoint PPT Presentation
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Homeostatic Control of Metabolism
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
Hypothalamic Centers• Feeding center – tonically active
• Satiety center – inhibits feeding center
Figure 11-3
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
Peptides Regulate Feeding
• Input to hypothalamus:– Neural from cerebral cortex– Neural from limbic system– Peptide hormones from GI tract– Adipocytokines from adipose tissue
Peptides Regulate Feeding
Note the diversity of peptide origins!
cholecystokinin =
Peptides Regulate Feeding
Figure 22-1
inhibition
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
Metabolism
= sum of all chemical reactions in the body
• Anabolic pathways – synthesize large molecules from smaller
• Catabolic pathways – break large molecules into smaller
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
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
Figure 22-2
CarbohydratesFats
Free fatty acids + glycerol
Fatstores
Glucose
Excess glucose
Glycogenstores
Aminoacids
Proteins
DIET
Lipogenesis
Brainmetabolism
Range of normalplasma glucose
Gluconeogenesis
Bodyprotein
Glycogenolysis
GlycogenesisProteinsynthesis
Metabolism inmost tissues
Free fattyacid pool
Urine
Excess nutrients
Lipolysis
Glucose pool
Amino acidpool
Lipogenesis
Many immediately
used
Excess stored
Excess converted in liver
Build proteins
Many immediately
used
Excess stored
What Controls This?
• Hormones control metabolism by altering enzyme activity and molecule movement
• Push-pull control: different enzymes catalyze forward and reverse reactions
Push-Pull Control
Figure 22-4
enzyme 1 enhanced, enzyme 2 inhibited
enzyme 1 inhibited, enzyme 2 enhanced
INSULIN
GLUCAGON
Metabolism is Controlled by Ratio of Insulin and Glucagon
Figure 22-9
Anabolic
Catabolic
Fed State
Many immediately used
Figure 22-7
Liverglycogen
stores
Energy production
Free fattyacids
Free fattyacids
Glycerol
Aminoacids
KetonebodiesGlucose
Adipose lipidsbecome freefatty acids andglycerol thatenter blood.
Muscle glycogen can be used for energy.Muscles also use fatty acids and breakdown their proteins to amino acids thatenter the blood.
Brain can useonly glucose andketones for energy.
or
Triglyceride stores
Glycogen
Pyruvate
Lactate
Energy production
Glucose
Proteins
Ketonebodies
Gluconeogenesis
Gluconeogenesis
1 2
34
Energyproduction
Liver glycogenbecomes glucose.
-oxidationGlycogenolysis
Fasted State
Pancreas – Islets of Langerhans
Figure 22-8
Insulin
• Origin in β cells of pancreas
• Peptide hormone• Transported dissolved
in plasma• Half-life ~5 min• Target tissues: liver,
muscle, adipose tissue
Insulin• Secretion promoted 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]
Insulin Mechanism of Action
PIRSIRS
Secondmessengerpathways
Transcriptionfactors
Enzymes or
Transportactivity
Changes inmetabolism
Nucleus
Extracellularfluid Insulin
GLUT4
Insulin binds to tyrosinekinase receptor.
Receptor phosphorylatesinsulin-receptor substrates (IRS).
Second messenger pathwaysalter protein synthesis andexisting proteins.
Membrane transportis modified.
Cell metabolism ischanged.
1
2
3
4
5
1
2
34
5
Figure 22-11
Insulin Lowers Plasma Glucose
1. Increases glucose transport into most insulin-sensitive cells
2. Enhances cellular utilization and storage of glucose
3. Enhances utilization of amino acids
4. Promotes fat synthesis
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
Insulin Increases Glucose Transport:Skeletal Muscle & Adipose Tissue
Figure 22-12GLUT-4 transporters moved to cell membrane
Insulin Increases Glucose Transport:Indirect in Liver Cells
Figure 22-13Insulin activates hexokinase, keeps IC [glucose] low
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
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
Insulin Promotes Fat Synthesis
• Inhibits β-oxidation of fatty acids
• Promotes conversion of excess glucose into triglycerides
• Excess triglycerides stored in adipose tissue
Figure 22-14
Glucose metabolism
Energy storage
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
Glucagon
• Secretion promoted by:– Low plasma [glucose] (< 100 mg/dL)– Increased plasma amino acids– Sympathetic input
• Secretion inhibited by increased [glucose]
• Inhibition by insulin??
Glucagon Raises Plasma Glucose
• Main purpose is to respond to hypoglycemia
• Activates enzymes for:– Glycogenolysis – glycogen breakdown– Gluconeogenesis – glucose synthesis
Figure 22-15
Response to Hypoglycemia in Fasted State
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
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
Figure 22-16
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?