Topic 85 - Insulin and glucagon

Question 1

Words to include in insulin

Answer 1

• Pancreas
• Plasma glucose concentration
• Anabolic storage processes
• Glucose - glycogen conversion
• B cells
• Pre-pro-insulin
  
  • C peptide
• Biphasic secretion

Question 2

Words to iclude in glucagon

Answer 2

• Pancreas
• Plasma glucose concentration redistribution
• Hepatic glycogen stores
• Carbohydrate stores
  
  • Liver
  • Muscle
• A cells
• Intestinal origin
• Pancreatic origin
• Plasma glucose level
• Glycogen synthesis
• Gluconeogenesis (GNG)

Question 3

Words to include in morphology of the pancreas

Answer 3

• Exocrine gland
  
  • Digestive enzymes
  • Buffers
• Endocrine gland
  
  • Islets of Langerhans
    
    • A cells
      
      • Glucagon
    • B cells
      
      • Insulin
    • D cells
      
      • Somatosin
    • F cells
      
      • Pancreatic polypeptide

Question 4

Words to include in regulation

Answer 4

• Regulation
• Paracrine activity
  
  • B cells
    
    • Hyperglycemia
    • Glucagon synthesis (↓)
  • Glucagon secretion
    
    • Hypoglycemia
  • A cells
  • D cells
  • Stimulation
  • Inhibition
• Plasma glucose
  
  • Glucose level
  • Amino acid level
  • Plasma
  • Feed-forward mechanism
    
    • Glucagon
    • Peptides
    • Insulin synthesis
    • Glucose loss
    • Glucose salvage
• Neural regulation
  
  • ANS
  • Sympathetic effect
    
    • Alpha receptor
      
      • Alpha-2 receptor
        
        • Insulin glucagon block
    • Beta receptor
    • Facilitation
    • Inhibition
    • Plasma glucose
    • Insulin release (ø)
  • Parasympathetic effect
    
    • Acetylcholine receptors
    • Vagus nerve - reflex arch
    • Feed-forward mechanism
  • B cell
  • A cell
• Insulin release
  
  • Biphasic
  • GIP
  • Enteroglucagon
  • Urine

Question 5

Words to include in stimulation of B cells

Answer 5

• Plasma levels
• GLUT 2 transporter
• Glucose
• Glucose-6-P
• Glucokinase activity
• Insulin secretion
• ATP
• ATP sesitive potassium channels
• Depolarization
• Calcium
• Enteroglucagon
• GIP
• cAMP system
• Pre-pro-insulin
• Blood vessel
• Immediate release
• De novo synthesis
• Immediate
• Insulin

Question 6

Words to inculde in effects of insulin

Answer 6

• Glucose uptake
  
  • Insulin dependent tissue
    
    • Vital tissue
      
      • Brain cells (GLUT1)
      • Red & white blood cells (GLUT1)
      • Brain capillaries (GLUT2)
      • Liver (GLUT3)
      • Basic uptake in muscle & adipose (GLUT1)
  • Insulin dependent tissue
    
    • Muscle
    • Adipose tissue
• Metabolic effect
  
  • Glycogen synthesis (↑)
  • Protein synthesis (↑)
  • Fat synthesis (↑)
  • Glucose utilization (↑)
    
    • Liver
    • Adipose
  • Carbohydrate metabolism
    
    • Amino acid
    • Proteins
    • Gluconeogenesis (GNG)
  • Lipid metabolism
    
    • Triglyceride synthesis
    • Lipid degradation
    • Fatty acid synthesis
    • AcetylCoA
  • Protein metabolism
    
    • Amino acid uptake
    • Protein synthesis (↑)
    • Protein degradation (↓)
    • Nitrogen balance +
• Insulin action
  
  • Dependent tissue
  • Adipose cell
    
    • Glucose entry (↑)
    • Triglyceride synthesis (↑)
    • Lipase activity (↓)
  • Muscle cell
    
    • Glucose entry (↑)
    • Amino acid entry
    • Protein synthesis (↑)
  • Liver
    
    • Glucose entry (ø regulated)
    • Glycogen synthesis (↑)
    • Glucose release (↓)
    • Ketogenesis (↓)
    • Gluconeogenesis (GNG) (↓)
  • Neuron
    
    • K⁺ entry (↑)
    • Hyperpolarization effects

Question 7

Words to include in glucose metabolism

Answer 7

• Intestinal tract
• Foodstuff glucose
• Plasma glucose
• Kidney
• Muscle
• RBC
• CNS
• Adipose
• H₂O
• CO₂
• Free fatty acids
• Lactic acid
  
  • Anaerobic conditions
• Liver
• Liver glucose
• AcCoA
  
  • Ketone bodies
  • Citric acid cycle activity (↓)

Question 8

Words to include in diabetes mellitus

Answer 8

• Diabetes mellitus
• Insulin deficiency
• Degradation of proteins
  
  • Nitrogen balance ÷
• Glucose
• Protein metabolism
  
  • Polyuria
  • Polydypsia
• Fat metabolism
  
  • Lipogenesis (↓)
  • Lipemia
  • Ketonemia
  • Ketonuria
  • Acidosis
• Carbohydrate metabolism
  
  • Hyperglycemia
  • Glycosuria, osmotic diuresis
  • Dehydration, hemoconcentration
  • Ketone substances (↑)
  • Blood pressure (↓)
  • Anuria
  • Coma
  • Exitus
• Diabetes type 1 (human)
• Diabetes type 2 (human)
• Diabetes type 3 (canine)

Question 9

Where are insulin and glucagon produced?

Answer 9

In the pancreas

Question 10

Main role of insulin and glucagon

Answer 10

Regulates plasma glucose concentration

Question 11

Insulin, general

Answer 11

• Anabolic storage processes
• Stimulating glucose glycogen conversion in cells (for storage)
• B cells
• Synthesized as pre-pro-insulin
  
  • C peptide cleaved at release
• Biphasic secretion
• Stimulation of anabolic and storage processes

Question 12

Glucagon, general

Answer 12

• Mobilizes hepatic glycogen stores
• Elevates plasma glucose concentration redistribution of carbohydrate stores from liver to muscle
• (glucagon + epinephrine prepares body for enhanced physical output)
• A cells
• Intestinal and pancreatic origin
• Acts only in liver
• Major role:
  
  • Increases plasma glucose level
  • Decreases glycogen synthesis
  • Stimulation of GNG

Question 13

Morphology of the pancreas

Answer 13

• The pancreas function both as an exocrine and endocrine gland:
  
  • Exocrine function of pancreas:
    
    • Digestive enzymes
    • Buffers
  • Endocrine function of pancreas:
    
    • Islets of Langerhans
• Four types of cells are present in the islets of Langerhans:
  
  1. A cells: Glucagon
  2. B cells: Insulin
  3. D cells: Somatostatin
  4. F cells: Pancreatic polypeptide (PP)

Question 14

Regulation

Types of regulation

Answer 14

1. Paracrine activity
2. Plasma glucose
3. Neural regulation

Question 15

Regulation

Paracrine activity

Answer 15

1. B cells, while releasing insulin into the bloodstream as the effect of hyperglycemia, exert a negative influence on the glucagon synthesis and secretion of A cells
2. Direct stimuli for glucagon secretion: hypoglycemia (low plasma glucose)
   
   • Glucagon stimulates:
     
     • Insulin secretion of B cells
     • Somatostatin production of D cells → inhibiting overproduction of itself
3. Somatostatin has a negative influence on the hormone production of A cells and B cells
   
   • Somatostatin protects the organism from glucagon and insulin overproduction
   • Somatostatin also decreases pancreatic polypeptide secretion of F cells

Green arrows = stimulation

Blue arrows = inhibition

Question 16

Regulation

Plasma glucose

Answer 16

• Production of hormones are influenced by glucose and amino acid levels of the plasma circulating in the pancreas:
  
  • High levels stimulate insulin secretion
  • Low levels stimulate glucagon secretion
• Feed-forward mechanism: Glucagon and other peptides stimulates insulin synthesis
• Glucose loss and glucose salvage

Question 17

Regulation

Neural regulation

Answer 17

• Synthesis of insulin and glucagon under control of ANS
• Sympathetic effect
  
  • ​Mediated by alpha and beta receptors
  • Complex facilitation/inhibition
    
    • Blocking through alpha2 receptors ensures high plasma glucose
    • Blocks insulin release (allows glucose uptake by muscle)
• Parasympathetic effect
  
  • Acetylcholine receptors
  • Vagus nerve – reflex arc
  • Feed-forward mechanism

Question 18

Stimulation of B cells

Answer 18

• Elevated plasma levels GLUT2 transportes allow B cells to take up glucose

1. Glucose-6-P levels of the cell will increase IC because of the high glucokinase activity
   
   1. Directly stimulates insulin secretion
2. Internalized glucose is utilized to produce ATP. Elevated ATP levels close ATP sensitive potassium channels,
   
   • Depolarization occurs
   • Influx of Ca²⁺ into the cell → release of insulin stores
3. Enteroglucagon and GIP enhance release of insulin and also initiate its synthesis through the cAMP system

Question 19

Effects of insulin

Answer 19

Glucose uptake:

• Insulin is involved in the regulation of glucose uptake into the cells
• Insulin independent tissues:
  
  • ​Vital tissues:
    
    • ​Brain (GLUT-1)
    • RBC and WBC (GLUT-1)
    • Brain capillaries (GLUT-2)
    • Liver (GLUT-3)
    • Basic uptake in muscle and adipose (GLUT-1)
  • Tisses metabolizing glucose can only take up glucose without the presence of insulin
• Insulin dependent tissues
  
  • ​All of the rest of the tissues:
    
    • Muscle
    • Adipose tissues

Metabolic effect:

• Insulin increases glycogen, protein and fat synthesis
• Increases glucose utlization in liver and adipose
• Carbohydrate metabolism:
  
  • ​Incororates amino acids into proteins (GNG)
  • Glucose levels ↓
• Lipid metabolism:
  
  • ​Triglyceride synthesis ↑
  • Lipid degradation ↓
  • FA synthesis from AcCoA
• Protein metabolism:
  
  • ​Stimulates amino acid uptake (ø hepatocytes)
  • Protein synthesis ↑
  • Protein degradation ↓
  • Positive nitrogen balance

Question 20

Insulin action on selected tissues

Answer 20

Question 21

Glucose metabolism

Answer 21

• Glucose, originated from the liver or absorbed from the intestines, elevates plasma glucose levels
• Glucose uptake of insulin dependent or independent tissues decreases plasma glucose levels
• Internalized glucose may be converted to CO_{^{<strong>2</strong>}} and water
  
  • ​Or among anaerobic conditions lactic acid is produced, which may be used to synthesize to glucose again
• If AcCoA is present in too high concentrations, ketone bodies appear
  
  • Citric acid cycle activity decreases

Question 22

Diabetes mellitus

Answer 22

• Insulin deficiency
• Degradation of proteins = negative nitrogen balance
• Cells unable to take up glucose (fasting on cellular level)
  
  • Elevated plasma glucose reabsorbing capacity of renal tubules is lost glucose in urine
• Types of diabetes:
  
  • Type 1
    
    • Juvenile
    • Insulin sensetive
  • Type 2
    
    • Adult
    • Insulin insensetive
  • Type 3 (canine)
    
    • Adult
    • Insulin sensitive