Control of Blood Glucose

Posted on January 12, 2013

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Control of Blood Glucose

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The Body Alternates Between Anabolic & Catabolic States

  • Anabolism: energy storage & growth
  • Catabolism: mobilization of stored energy to support body functions
  • We use energy continuously but take it in only during meals
  • During and immediately following a meal the body goes into an anabolic state & stores energy:

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  • Anabolic activities are supported by the hormone insulin
  • Between meals the body goes into the state of catabolism: it breaks down glycogen, triglycerides and sometimes protein to provide energy
  • Catabolism is supported by the hormones glucagon and growth hormone
  • In exercise or stressful situations epinephrine and cortisol increase the rate of catabolism

The Brain Requires Blood Glucose

  • The brain is the organ most sensitive to glucose
  • Brain requires a constant supply of blood glucose
    • Normally glucose is the only energy source for the brain
    • In starvation brain will adapt to use some ketones
  • Hypoglycemia = low blood glucose; sometimes caused when diabetic takes too much insulin (insulin shock)
    • Symptoms: mental confusion, slurring of speech -> coma -> death
    • Treatment: give glucose

Blood Glucose is Controlled Mainly by the Liver

  • Immediately after meals blood glucose comes from meal
  • Between meals blood glucose comes from the liver & kidneys
    • Only the liver and kidneys can release glucose into the blood (requires a special enzyme that converts glucose metabolites to glucose, which can be transported across the cell membrane)
    • Liver provides 80% of blood glucose supply between meals, the kidney 20%
  • Liver makes glucose in 2 ways:
    • Breaks down liver glycogen (glycogenolysis)
    • Converts other types of small molecules into glucose (gluconeogenesis)
      • Gluconeogenesis requires 4 special enzymes which can reverse some of the reactions of glycolysis
      • Many small molecules can be converted to glucose:
        • Lactate & pyruvate: mainly come from muscles
        • Glycerol: supplied by adipose tissue when triglycerides are broken down-
          • Fatty acids cannot be converted into glucose, but:
          • Fatty acid metabolism indirectly supports gluconeogenesis by producing AcetylCoA
          • AcetylCoA activates and inhibits key enzymes, promoting glucose formation
        • Amino acids: 20 of the 22 amino acids can be coverted to glucose

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  • Figure shows rate of glucose delivery to the blood by the liver (Data from: Keith N. Frayn. Metabolic Regulation, 1997)
  • Delivery of glucose to the blood is controlled by insulin, glucagon and other hormones
  • Brain receives a constant 80 mg/min (doesn’t change much in exercise)
  • Amount delivered to other tissues depends upon body state (rest vs exercise)
    • At rest total glucose output to the blood is about 130 mg/min (80 to brain, 50 to other tissues)
    • During exercise total can increase to about 2500 mg/min

The Only Hormone that Can Lower Blood Glucose is Insulin

  • Muscle, fat and liver tissues require insulin to transport insulin into the cells; in these tissues insulin seems to increase the number of glucose transporters in the cell membrane
  • Many other tissues, including brain, do not require insulin to transport glucose
  • Insulin also increases activity of enzymes that cause storage of sugar as glycogen or lipid
  • After a meal blood sugar rises and this stimulates the release of insulin from the pancreas;
  • Extra insulin then causes the sugar to enter the cells and become stored

Both Insulin and Glucagon are Made in the Endocrine Part of the Pancreas

  • The pancreas has both an exocrine and endocrine part
    • Endocrine part: small clumps of cells called islets of Langerhans
    • Exocrine part: makes digestive enzymes, delivers them to duodenum through ducts
  • Endocrine part: makes glucagon, insulin, secretes them into blood
  • If blood sugar is high secretes large amounts of insulin, small amounts of glucagon
  • Secretion reversed when blood sugar is low
  • Glucagon raises blood sugar, insulin lowers it

Several Hormones Can Raise Blood Glucose

  • Four major hormones raise blood glucose:
    • Glucagon
    • Cortisol
    • Epinephrine
    • Growth hormone
  • In vigorous exercise all 4 of these hormones increase

Diabetes Mellitus Results When Insulin is Deficient or Ineffective

  • Diabetes = excess production of urine
  • Mellitus = sweet (refers to sugar in urine)
  • Two types of diabetes mellitus:
    • Type I: autoimmune destruction of pancreatic cells, usually occurs early in life. Characterized by low insulin output, high blood glucose, glucose in urine, excess urine flow, switch to fat metabolism. Treated with insulin injections, careful balance of diet & exercise.
    • Type II: associated with obesity, usually starts later in life. Insulin may be normal, but is ineffective (insulin resistance). Many of symptoms the same, but less severe. May be reversed if weight is lost. Cause unknown, but may be receptor disease.

If Blood Sugar is Too High Some Will Spill Into the Urine

  • Kidney filters glucose into tubules and then reabsorbs it (100% in normal person)
  • If glucose concentration is too high reabsorption cannot keep up with filtration and some glucose stays in tubule and becomes part of urine
  • Glucose in the urine will suck more water into the urine (osmosis) and cause excess urine production (diabetes); body will be dehydrated -> thirst
  • Urine glucose test useful in diagnosing diabetes
    • Measured with Benedict’s reagent or glucose oxidase enzyme

Diabetes is Sometimes Called “Starvation in the Midst of Plenty”

  • A diabetic has plenty of sugar in his blood but many of his tissues cannot use it because it can’t get into the cells
  • Glucose is water soluble and cannot cross cell membranes by simple diffusion
  • Insulin stimulates sugar transport into muscle, and fat cells (but not into brain cells)
    • Causes insertion of GLUT4 transport molecules into membranes of muscle and adipose tissue
    • Brain has its own transporter, GLUT3; not insulin dependent
  • In diabetes cells must look for alternate sources of energy

When the Body Can’t Burn Glucose it Switches to Fat Metabolism

  • If muscle cells can’t get enough glucose body will increase fat breakdown to provide free fatty acids (FFAs) as an energy source
  • Remember: brain cannot use FFAs
  • A side reaction of excess lipid metabolism is the build-up of ketoacids in the blood
    • Ketoacids can be smelled on breath: odor similar to acetone
    • Ketoacids disturb mental functions and lower blood pH

Diabetics May Have Poor Circulation

  • Excess sugar makes the blood syrupy (more viscous): harder for heart to pump
  • Excessive urine flow dehydrates body, reduces blood volume
  • Both effects reduce the circulation

Diabetic Ketoacidosis is a Medical Emergency

  • If a diabetic lets his blood sugar get too high he may develop ketoacidosis, a life-threatening emergency
  • Most of the problems in ketoacidosis are due to:
    • Dehydration (due to excessive urine production)
    • Low pH (due to excessive lipid metabolism)
    • Large amounts of ketoacids in the blood (also due to excessive lipid metabolism)

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