Lecture 22

• Hormones


  Small molecules or proteins that are produced in one tissue, released into the bloodstream, and carried to other tissues
• Neuroendocrine system


  The system that coordinates metabolism in mammals

  
• 4 general types of intracellular consequences of ligand-receptor interaction


  • Generation of a second messenger that acts as an allosteric regulator of one or more enzymes
  • Activation of a receptor tyrosine kinase
  • Opening or closing of an ion channel causes a change in membrane potential
  • A nuclear hormone receptor protein mediates a change in gene expression
• Water-insoluble hormones


  Readily enter the cell and bind receptor proteins in the nucleus to alter the expression of specific genes
• Peptide hormones


  Hormones that are synthesized as proproteins (prohormones) that are activated upon release by proteolytic cleavage
• Insulin


  • A small protein with two polypeptide chains, A and B, joined by two disulfide bonds
  • Synthesized on ribosomes in the pancreas as preproinsulin
  • Stored as proinsulin in secretory vesicles
  • Converted to active insulin by proteases when blood glucose is sufficiently elevated

  
• Adipokines


  Peptide hormones produced in adipose tissue that signal the adequacy of fat reserves
• Adipokines


  • Leptin
  • Adiponectin
• Leptin is released when adipose tissue is well-filled with triacylglycerols

  Inhibits feeding
• Adiponectin is released when adipose tissue is depleted of fat reserves


  Stimulates feeding

  
• Ghrelin


  Produced in the gastrointestinal tract when the stomach is empty, stimulates feeding
• Incretins


  Peptide hormones produced in the gut after ingestion of a meal, increases insulin secretion and decreases glucagon secretion

  
• Myocytes (skeletal muscle cells)


  • Metabolism promotes the generation and usage of ATP for contraction
  • Creatine kinase uses phosphocreatine to rapidly regenerate ATP from ADP, and during recovery works in reverse to use ATP to regenerate phosphocreatine from creatine

  
• The brain requires a continuous supply of glucose and uses it for transmission of electrical impulses
• Blood carries oxygen, metabolites, and hormones
• 3 types of blood cells

  • Erythrocytes (red cells) - filled with hemoglobin and specialized for carrying O2 and CO2
  • Leukocytes (white cells) - central to the immune system to defend against infections (e.g. lymphocytes)
  • Platelets (cell fragments) - help to mediate blood clotting
• Insulin release


  Stimulates glucose uptake, lowering blood glucose

  
• Adipose negative-feedback model


  Suggests that eating behavior is inhibited and energy expenditure is increased whenever body weight exceeds a certain "set point" value
• Leptin


  An adipokine produced by adipose tissue that regulates feeding behavior and energy expenditure to maintain adequate reserves of fat

  
• Adiponectin


  • Stimulates fatty acid uptake and oxidation
  • Inhibits fatty acid synthesis
  • Sensitizes muscle and liver to insulin

  
• AMP-activated protein kinase (AMPK)


  Mediates many effects of adiponectin

  
• Ghrelin


  A peptide hormone produced in cells lining the stomach, an appetite-stimulant
• Diabetes mellitus


  A relatively common disease affecting around 9% of the U.S. population
• 2 major clinical classes of diabetes mellitus


  • Type 1 diabetes (insulin-dependent diabetes mellitus (IDDM))
  • Type 2 diabetes (non-insulin-dependent diabetes mellitus (NIDDM))

  
• Type 1 diabetes


  • Stems from an autoimmune destruction of pancreatic β cells, resulting in the inability to produce sufficient insulin
  • Begins early in life
  • Responds to insulin injection

  
• Type 2 diabetes


  • Slower to develop and typically in obese adults
  • Responds to insulin injection

  
• Both types of diabetes are characterized by excessive thirst and frequent urination; unable to take up glucose efficiently from the blood

  
• Pathology of diabetes includes cardiovascular disease, renal failure, blindness, neuropathy
• Glucose-tolerance test


  Measures the blood glucose after an overnight fast and after drinking glucose water

  
• Carboxylic acids (ketone bodies) accumulate in the blood of those with untreated diabetes, leading to excessive but incomplete oxidation of fatty acids in the liver

  
• Metabolic syndrome


  The stage preceding type 2 diabetes, includes obesity, hypertension, abnormal blood lipids, high fasting blood glucose, and reduced ability to clear glucose