Physiology - Endocrine - Pancreas

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  1. Insulin and glucagon control fuel flow and utilization
    Three principal tissue types involved:
    Metabolite targets include:
    Effects
    • Liver, Muscle, Adipose
    • Glucose, Amino acids, Free fatty acids, Ketoacids
    • Insulin: anabolic; lower glucose, AA, FFA, ketoacids; stim liver form glycogen, muscle form glycogen and protein, adipose form fat
    • Glucagon: catabolic; increase glucose, ketoacids; stim liver gluconeogenesis, break down glycogen, adipose lipolysis
  2. The bulk of the pancreas serves _____. The endocrine functions are performed by _____, small groups of cells scattered through the pancreas, representing about 2% of pancreatic mass.
    • an exocrine organ
    • Islets of Langerhans
  3. Cell types of the Islets of Langerhans:
    • Alpha cells (a-cells, A cells): 20% of islet, secrete glucagon. Inc. plasma glucose and mobilize hepatic glycogen & fat.
    • Beta cells (b-cells, B cells): 60-75% of islet, secrete insulin. Inc. cellular glucose uptake and deposition of glycogen & fat.
    • Delta cells (d-cells, D cells): <5% of islet, secrete somatostatin. Dec. insulin & glucagon secretion and exocrine gastric secretions.
    • F cells: <5% of islet, secrete pancreatic polypeptide. Dec. food absorption.
  4. Synthesis of insulin
    • 1. transcription and translation of the signal sequence
    • 2. translocate to RER, continue translation the full sequence, pre-proinsulin, cleavage of signal sequence, forming proinsulin
    • 3. in golgi, cleavage of C-peptide, A-B chains bind forming active insulin
    • 4. packaged in secretory granules, C-peptide and insulin, high Zn stabilize the peptide
    • 5. release into blood
  5. The half-life of insulin in the circulation is ____.
    ~5 min
  6. C-peptide offers a useful measure of ______ in patients under ______, because it is released in direct proportion to endogenous insulin generation but is not present in the injected insulin.
    • pancreatic Beta cell function
    • insulin therapy
  7. The principal mechanism for control of plasma glucose levels:
    Normally _____ plasma lvl
    As glucose increases, ______ secretion is stimulated.
    When plasma glucose falls below the normal range, ______ secretion is increased.
    • 5.5 mM (100 mg/dL)
    • insulin
    • glucagon
  8. ________ condition occurs during a long term fast, and insulin lvl ___________.
    • Hypoglycemic
    • drops below baseline level
  9. Mechanism of glucose regulation of insulin secretion
    • Glucose enters Beta-cells via GLUT2 transporters
    • glycolysis & citric acid cycle
    • increased ATP lvl
    • inhibits ATP-sensitive K+ channels, shuts off K+ efflux
    • depolarizes the B cell
    • stim Ca2+ influx
    • stim release of insulin by exocytosis
  10. Factors affecting insulin secretion: stimulators
    • GLUCOSE
    • Amino acids (leucine, arginine, others)
    • β-Keto acids
    • Glucagon, GLP-1, GIP
    • Sulfonylureas (blocks KATP channels)
  11. Factors affecting insulin secretion: inhibitors
    • 2-Deoxyglucose
    • Somatostatin
    • α-Adrenergic agonists
    • Diazoxide (opens KATP channels)
  12. Insulin action on cells: Binding of insulin to its receptor causes ________ of the receptor, which then acts as a _______ that phosphorylates ______, which then _______ in other proteins and enzymes. Numerous target enzymes are ultimately activated or inactivated, and the result is to stimulate _______. Transport of amino acids, potassium, magnesium, and phosphate is facilitated by other mechanisms. The synthesis of various enzymes is induced or suppressed by changes in gene expression.
    • autophosphorylation
    • tyrosine kinase
    • tyrosines in insulin receptor substrates
    • phosphorylate serine and threonine residues
    • glucose metabolism
  13. Mechanism of insulin activation of glucose transport: Cycling of _____ through _____ in insulin-sensitive tissues. Activation of the insulin receptor causes activation of _____, which speeds translocation of the _____. The GLUT4 transporters then mediate glucose transport into the cell.
    • GLUT 4 transporters
    • endosomes
    • phosphoinositide 3-kinase
    • GLUT4-containing endosomes into the cell membrane
  14. Glucose transporter families
    • Active Na+-glucose cotransport: SGLT1 and 2 - active glucose absorption in gut and kidney
    • Facilitated diffusion GLUT:
    • GLUT2: B cells of islets, liver
    • GLUT4: Insulin-stimulated glucose uptake; located in Skeletal and cardiac muscle, adipose tissue, other tissues
  15. Principal actions of insulin: Rapid (seconds)
    Increased transport of glucose, amino acids, and K+ into insulin-sensitive cells
  16. Principal actions of insulin: Intermediate (minutes)
    • Stimulation of protein synthesis
    • Inhibition of protein degradation
    • Activation of glycolytic enzymes and glycogen synthase
    • Inhibition of glycogen phosphorylase and gluconeogenic enzymes
    • Increased lipogenesis, inhibition of lipolysis
  17. Principal actions of insulin: Delayed (hours)
    Increase in mRNAs for lipogenic and other enzymes
  18. Glucagon is a _____ hormone synthesized in the ____ cells of the _____ pancreas.
    • It is synthesized initially as a ______.
    • Glucagon has a half-life of ___, and is degraded by ______.
    • peptide
    • Alpha
    • endocrine
    • preprohormone
    • 5-10 min
    • its major target organ, the liver
  19. organs other than the liver are exposed to relatively low levels of glucagon because
    glucagon is released directly into the portal vein and is degraded by liver
  20. Glucagon release is inhibited by plasma glucose over a range between ________ to ____. Therefore, the regulation of glucagon by glucose is well tailored to its glycogenolytic and gluconeogenic actions to _______ from liver.
    • hypoglycemic
    • normal
    • increase glucose release
  21. Stimulators of glucagon secretion
    • Amino acids (particularly glucogenic AAs, eg. alanine, serine, glycine)
    • Acetylcholine
    • β-Adrenergic agonists
    • Cortisol
    • Exercise
  22. Inhibitors of glucagon secretion
    • GLUCOSE
    • Free Fatty Acids
    • Ketones
    • Somatostatin
    • Insulin
  23. effect of glucagon:
    • stimulate the generation of glucose from glycogen and amino acids in liver
    • mobilize fatty acids and stimulate their conversion to ketoacids
  24. Somatostatin is produced in ______ of the pancreas, but is also formed in other locations including the ______. Its release is stimulated by ___________.
    • Delta-cells
    • hypothalamus
    • the same stimuli that increase insulin secretion, particularly glucose and amino acids
  25. The principal effect of pancreatic somatostatin is to _________. This appears to rely on a _______ action, perhaps acting predominantly _______.
    • inhibit the release of other islet hormones, most importantly insulin and glucagon
    • paracrine
    • within a single islet of Langerhans
  26. In the GI-tract, somatostatin has effects to _________.
    decrease glucose transport across gut wall and to decreased blood flow
  27. Metabolic effects of epinephrine (NE has a lesser role in regulating metabolism):
    • stims glucose production from gluconeogenesis (liver) and glycogenolysis (liver & muscle)
    • Stim Lipolysis and ketogenesis
    • stims lactic acid -> glucose, important to active muscles
    • inhibits the action of insulin to stimulate glucose uptake (muscle and fat).
    • OVERALL increases in plasma levels of glucose, free fatty acids, and ketoacids.
  28. The major effect of cortisol is to __________. The glucose is stored as ______ and released for use by other tissues
    • stimulate the mobilization of amino acids (primarily from muscle, wasting of muscle) and their conversion to glucose (liver)
    • glycogen
  29. Cortisol ____ the stimulation of glucose uptake by insulin in peripheral tissues (muscle and fat).
    Cortisol causes _____ of fat from adipose tissue, but can also ______ in selected adipose tissue sites.
    • inhibits
    • mobilization
    • facilitate fat storage
  30. Compare to glucagon, cortisol is
    • same: hyperglycemic (it increases blood glucose).
    • differ: unlike acute hyperglycemic hormones (glucagon and epinephrine), it stims the deposition of glycogen
  31. Leptin is a _____ hormone produced by ______. It is formed and secreted in proportion to _______, thus "report" the size of the adipose mass to the hypothalamus and other brain areas.
    • peptide
    • adipose tissue
    • the amount of adipose tissue
  32. When excessive food intake leads to an increase in adipose mass, the plasma level of leptin _______, and this leads to a series of behavioral and metabolic changes designed to _______, such as to _________________.
    • increases
    • reduce adipose mass
    • reduce appetite
    • increase basal energy expenditure
    • obligatory thermogenesis
    • modulate the secretion of hormones to decrease lipogenic activity and increase lipolytic activity of adipose tissue
  33. Blood glucose
    • GH +
    • E +
    • Cortisol +
    • Glucagon +
  34. Glucose uptake
    • GH -
    • E -
    • Cortisol -
    • Glucagon none
  35. Glycogenesis
    • GH +
    • E -
    • Cortisol +
    • Glucagon -
  36. Glycogenolysis
    • GH -
    • E +
    • Cortisol -
    • Glucagon +
  37. Gluconeogenesis
    • GH +
    • E +
    • Cortisol +
    • Glucagon +
  38. Glycolysis
    • GH -
    • E +
    • Cortisol -
    • Glucagon -
  39. Protein
    • GH +
    • E none
    • Cortisol -
    • Glucagon -
  40. Fat
    • GH -
    • E -
    • Cortisol +
    • Glucagon -
  41. A common cause of hypoglycemia is ______. The brain is particularly sensitive to hypoglycemia, because ________.
    • excess insulin due to improper self administration
    • it has little stored carbohydrate and depends almost exclusively on glucose for its energy source
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316913
Card Set
Physiology - Endocrine - Pancreas
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Physiology - Endocrine - Pancreas
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