Regulation of Blood Glucose

Question 1

blood glucose must be closely maintained at what concentration?

Answer 1

60-100 mg/dL

4.5-5.5 mM

Question 2

liver

• insulin dependent or independent?
• has capacities for what metabolic capacities?
• relies predominantly on what fuel sources?

Answer 2

• insulin dependent
• capable of
  
  • gluconeogenesis - unique to liver*. using substrates from elsewhere
  • glycogen storage - for other tissues: using glucose-6-phosphotase
  • TAG synthesis
  • ketone body synthesis
• relies on: mostly FAs
  
  • glucose (in first 4 hrs post meal) + FA oxidation

Question 3

muscle/heart

• insulin dependent or independent?
• capacities?
• relies on what fuel?

Answer 3

• insulin dependent
• capacities:
  
  • glycogen synthesis - for self (does not have glycogen-6 phosphorylase)
  • produces gluconeogenic substrates: alanine, lactate - does not itself do gluconeogenesis
• reslies on: glucose, FAs
  
  • active muscle: aerobic + anaerobic glycolysis
  • resting muscle: fatty acids*

Question 4

adipose tissue

• insulin dependent or independent?
• has what capacities?

Answer 4

• insulin dependent
• capacities:
  
  • produces:
    
    • FAs - TAG synthesis in liver
    • glycerol-3-P - TAG synthesis in liver
      
      • as a gluconeogenic substrate (through DHAP)
  • stores: FAs

Question 5

brain

• insulin dependent or independent?
• capacities?
• relies on what fuels?

Answer 5

• insulin independent
• relies on: glucose, ketone bodies
  
  • glucose: the brain relies on glucose in all states
    
    • HEAVILY in most states
  • ketone bodies: are utilized in in severe fasting state, though never exclusively

Question 6

erythrocytes

• insulin dependent or independent?
• has what capacities?
• relies on what fuels?

Answer 6

• insulin independent
• capacities:
  
  • produces gluconeogenic substrate - lactate
  • uses 2,3- BPG to
    
    • modulate HbO2 affinity
    • reflect blood glucose levels
• relies on: anaerobic glycolysis excusively - has no mitochondria

Answer 7

phase 1: 0-4 hrs. only time liver uses glucose as fuel

phase 2: 4-16 hrs. exogenous source depleted, glycogen > gluconeogenesis

phase 3: 16-32 hrs: gluconeogenesis > glycogen

phase 4: > 32 hrs: brain starts using ketone bodies

Question 8

what two tissues can take up glucose inependent of insulin?

Answer 8

1. brain
2. RBCs

Question 9

glucocorticoids

• secreted by what tissue?
• have what effects on blood glucose?

Answer 9

• by adrenal cortex (zone fasculata) in when blood glucose low
• effects:
  
  • inreases gluconeogenesis
  • inhibits glucose uptake in tissues

Question 10

growth hormone

• secreted by what tissue?
• has what effects on blood glucose?

Answer 10

• by somatrophes (ant pit) during low BP
• decreases glucose uptake by muscle

Question 11

mature granules in beta cells contain what?

what stimulates their degranulation & how?

Answer 11

• contain equal parts INSULIN + C-PEPTIDE
• release contents in response:
  
  • hyperglycemia:
    
    • via GLUT-2 receptors that detect
      
      • glucose
      • glucokinase
  • ACh / arginine / FAs

Question 12

how is insulin synthesized?

Answer 12

• as preproinsulin on RER
• preprosinulin –> proinsulin
• proinsulin –> insulin by two protelytic activities (removing each side of the C-peptide)

Question 14

describe the structure of the insulin receptor

Answer 14

• two paired subunits
  
  • alpha - extracellular
  • beta - transmembrane
    
    • associated with Tyr residues w/ tyrosine kinase activity

Question 15

discuss the phosphorylation of Tyr residues on the insulin receptor.

how do different stimuli effect Tyr phosphorylation, and how does this modulate its activity?

Answer 15

• insulin binding: causes autophosphorylation of Tyr residues –> activing their tyorine kinase activity and cascade
• cAMP activity: PKA phosphoryolates Ser/Thr tresidues –> which inhibits tyrosine kinase acitivity

Question 16

summarize the effects of insulin on glucose metabolism

Answer 16

overall effect: decreases blood glucose

• stimulates:
  
  • glycolysis
    
    • ex:
      
      • + glucokinase in the liver
      • + F, 26-BP
  • glycogenesis - in liver, muscle
  • glucose transport - into muscle, adipose tissue by promoting addition of GLUT-4 into their membranes
• inhibits:
  
  • gluconeogenesis in the liver

Question 17

other than glucose, insulin also stimulates transport of?

Answer 17

aas / nucleosides / Ca++ / PO4 / K+

Question 18

summarize the effects of inuslin on lipid metabolism

Answer 18

• stimulates:
  
  • lipogenesis - in liver, adipose
  • fatty acid uptake from serum (blood)
    
    • for lipogenesis
• inhibits:
  
  • lipolyis

Question 19

insulin effects on protein / nucleic acid synthesis

Answer 19

• promotes protein synthesis
• promotes nucleic acid (DNA, RNA) synthesis

Question 20

glucagon

• synthesized by what cells & how?
• in response to?
• acts on what targets?
  
  • and has what effects?
  • how?

Answer 20

• by a-cells in pancreas as a prepropeptide
• in respone hypoglycemia
• effects:
  
  • stimulates
    
    • glycogenolysis - liver, adipose
    • gluconeogenesis - liver
  • inhibits
    
    • glycolysis
• via Gs (GCRP) -adenylate cyclas/cAMP

(cannot act on muscle)

Question 21

epinephrine

• synthesized by what cells?
• in response to?
• acts on what tissues?
  
  • has what effects?
  • how?

Answer 21

• by adrenal medulla cells
• in response to hypogycemia & fear / excitement
  
  • in liver
    
    • stimulates
      
      • gluconeogenesis
      • glycogenolysis
    • inhibits
      
      • glycolysis - 1. can’t go on at the same time as gluconeogenesis & 2. want to mobilize glucose to other tissues
  • in muscle
    
    • stimulates
      
      • glycogenolysis
      • glycolysis - muscle uses glucose from glycogen breakdown for itself
    • inhibits
      
      • glucose uptake into muscle - muscle will use glucose from glycogen/the liver instead, to get blood glucose back up
• via cAMP (like glucagon)

Question 22

summarize the key differences between glucose metabolism under regulation in insulin vs glucagon predominant state

Answer 22

insulin

• syntheis of protein, fat, glycogen (liver, muscle)
• fat stored in adipose tissue

glucagon

• breakdown of glyogen (liver, muscle)
• mobilization of alanine, lactate for gluconeogenesis

Question 23

what can an excesss of insulin administration lead to?

Answer 23

hypoglycemia

Question 24

what is glucosuria and at what blood glucose level does it present?

Answer 24

• when glucose is present in the urine
• seen when r_enal threshold is exceded:_ > 150 mg/ 100 mL

Question 25

what is the purpose of a oral glucose tolerance test (OGTT)?

Answer 25

gold standard to dx diabetes

• persistently high blood glucose ( > 6% glycosylated Hb) following glucose amdinistration indicates poor sensitivity to insulin.