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29 Cards in this Set
- Front
- Back
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Communication b/w Tissues
- 4 main organs that play dominant role in fuel metabolism - 3 ways |
- 4 organs: liver, adipose, muscle, and brain
- 3 ways: hormones, nervous system, and availability of circulating substances |
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Each organ is specialized for what three things?
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- storage, use, and generation of specific fuels
*these tissues don't work in isolation; part of network where one provides substrates for another |
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Energy metabolism controlled by what two hormones and supported by what two hormones?
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- controlled: insulin + glucagon (peptide hormones)
- supported: epinephrine + norepinephrine *changes in levels of these hormones allows body to store energy or make stored energy available |
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Insulin
- type of hormone - location - metabolic effects |
- polypeptide hormone
- produced/secreted by beta cells of islets of Langerhans (exocrine portion of pancreas) - metabolic effects = anabolic *synthesis of glycogen, triacylglycerols, and proteins |
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Structure of Insulin
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- 51 A.A. in two polypeptide chains
* chains A & B linked by two disulfide bridges * A also has internal disulfide bridge - beef insulin differs by 3 A.A. - pork insulin differs by 1 A.A. |
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Synthesis of Insulin
- simplistic - detailed |
- simplistic: preproinsulin (signal sequence removed in ER) => proinsulin => golgi aparatus where converted to insulin + C-peptide
- detailed: *genes for insulin transcribed into mRNA in nucleus *translation in cytoplasmic ribosomes w/ N-terminus signal sequence for transport to RER *finishes translating in RER to preproinsulin *signal peptide cleaved => proinsluin in cisternal space *transported to golgi where cleaved to form insulin *secretory granule released w/ insulin + C-peptide *granules undergo exocytosis |
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What three factors stimulate insulin synthesis and secretion?
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- insulin and glucagon release always coordinated
- insulin synthesis and secretion stimulated by: *glucose *amino acids (esp. arginine) *gastrointestinal hormones (secretin) |
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Effects of Glucose Ingestion
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- beta cells are most glucose-sensing cells in the body
*contain glycokinase which phosphorylates gucose in amounts equal to its blood concentration - glucose is most important stimulus for insulin secretion |
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Changes in blood levels of glucose, insulin, and glucagon after ingestion of a carbohydrate-rich meal
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- glucose and insulin levels go up
- glucagon levels go down |
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What three factors inhibit insulin secretion?
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- low fuels
- stress (fever/infection) - epinephrine (trauma/extreme exercise) |
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What three tissues are primarily effected by insulin and what are the effects?
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(1) LIVER = inhibits gluconeogenesis + stimulates glycogen synthesis
(2) MUSCLES = increase glycogen synthesis + glucose uptake by increase number of transporters (3) ADIPOSE = increase glucose uptake |
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Effects of Insulin on Fatty Acids
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- significant reduction in release of F.A.
*triacylglycerol degradation decreased (inhibits lipase) *increased triacylglycerol synthesis (increase glucose transport and metabolism in adipose tissue to produce glycerol 3-phosphate - precursor of triacylglycerol synthesis) |
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Trend of Insulin
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- insulin causes uptake of glucose to store a glycogen in liver + muscles or triacylglycerols in adipose tissue
*promotes metabolic pathways that involve storing energy |
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What are the characteristics of insulin receptors?
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- high affinity
- glycosylated, sinlge polypeptide, alpha & beta subunit, tetramer linked by disulfide bonds - alpha subunit = insulin binding site - beta subunit = hydrophobic; has tyrosine kinase activity that's activated by insulin |
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Mechanism of Insulin Receptor Action
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insulin binds to alpha subunit => causes conformational change in beta subunit => autophosphorylation of tyrosine residues => cascade of cell signaling responses => phosphorylation of insulin receptor substrate (IRS) protein => biological actions of insulin
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Membrane Effects of Insulin
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- insulin-sensitive glucose transporters (GLUT-4) recruited in skeletal muscle and adipose tissue
*insulin binds to cell membrane receptor => glucose transporters (GLUT-4) move to cell membrane => glucose transporters increase glucose into cell => when glucose levels decrease, GLUT-4 leaves membrane => vesicles fuse to form endosomes |
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Name 6 tissues that DO NOT require insulin for glucose transport
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(1) heptocytes (of liver)
(2) erthyrocytes + leukocytes (3) cells of nervous system (brain) (4) cornea/lens of eye (5) intestinal mucosa (6) renal tubules |
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How is the insulin receptor "down-regulated"?
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- receptor containing bound insulin endocytosed by cell
- insulin degraded in lysosomes - receptor degraded or recycled |
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Time Course of Insulin Action
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- an increase in GLUT-4 transporters in skeletal muscle and adipose tissue takes only seconds
- other enzymatic actions could take hours to days |
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Characteristics of Glucagon
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- 29 A.A. polypeptide secreted by alpha-cells of pancreatic islets of Langerhans
- all mammalian species have same sequence - opposes many action of insulin - counterregulatory hormones = along w/ epinephrine, cortisol, and growth hormone - main job = prevent hypoglycemia (low blood sugar) by initiating certain metabolic pathways |
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List three stimuli for glucagon secretion
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(1) low blood glucose (primary stimuli)
(2) amino acids (glucagon secreted w/ insulin to prevent hypoglycemia) (3) epinephrine (during stress/exercise, glucagon secreted in anticipation of increased glucose use) |
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List two factors that inhibit glucagon secretion
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(1) increased blood glucose
(2) insulin |
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List three metabolic effects of glucagon
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(1) increase blood glucose concentration by initiating gluconeogenesis and glycogenolysis in liver
(2) hepatic oxidation of fatty acids (increases ketone bodies from acetyl CoA) (3) increased amino acid uptake by liver (provides C skeletons for gluconeogenesis) |
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Mechanism of action of glucagon
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(1) binds to high-affinity receptors on hepatocytes
(2) adenylyl cyclase activated in plasma membrane (3) elevated cAMP levels (4) activated protein kinases (5) cascade of carbohydrate and lipid metabolism |
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What are 5 characteristics of hypoglycemia?
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(1) confusion, aberrant behavior (possible coma)
(2) blood glucose levels < 40 mg/dl (3) symptoms being resolved within minutes of glucose ingestion (4) considered medical emergency b/c CNS demands constant supply of blood-borne glucose (5) prevented by glucagon and epinephrine |
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Symptoms of Hypoglycemia (2)
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- adrenergic = anxiety, sweating, tremors, palpitations [mediated by epinephrine when blood glucose levels fall abruptly]
- neuroglycopenia = lack of glucose to brain; headache, confusion, slurred speech, seizures, coma and possibly death; resultant of gradually diminished glucose levels |
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Glucoregulatory Systems
- Islets of Langerhans - Receptors in Hypothalamus |
- islets of langerhans release glucagon [for glycogenolysis, gluconeogenesis] in response to hypoglycemia
- receptors in hypothalamus mediate release of epinephrine [for glycogenolysis], ACTH [for glyconeogenesis], and growth hormone |
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List and describe three types of hypoglycemia
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(1) insulin-induced = diabetics that have administered too much insulin (Tx: eat carbs)
(2) postprandial = caused by exaggerated insulin release after meal; mild adrenergic symptoms induced (Tx: eat smaller meals) (3) fasting = usually seen in patients w/ hepatocellular damage or alcoholics *liver unable to produce adequate glucose levels during periods of fasting *also, a beta-cell tumor could cause increased insulin secretion which would over-utilize blood glucose concentration |
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Hypoglycemia and Alcohol Intoxication
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- ethanol => acetaldehyde => acetate (both rxns produce NADH)
- increase in NADH: pyruvate => lactate & oxaloacetate => malate - so, pyruvate and oxaloacetate unable for gluconeogenesis resulting in hypoglycemia *Disulfiram = drug that inhibits aldehyde dehydrogenase (enzyme that converts acetaldehyde to acetate during ethanol meabolism) *elevated acetaldehyde levels cause extreme nausea *alcoholics who want to stop drinking take Disulfiram - alcohol consumption can cause dangerous hypoglycemia in individuals who: *have exercised strenuously for prolonged period of time *are fasting *taking insulin for diabetes |
