MT 6 - Endocrinology Flashcards

1
Q
  1. Classification of hormones, the dynamics of the receptor ligand interaction, the feedback mechanism:
    Classification of hormones
A
  1. Lipid-soluble - E.g. steroid
    - Lipophilic-easily pass plasma membr. and act IC
    - Carrier proteins->long half-life in plasma
    - Directly act on nucleus
    - IC mediator: receptor-hormone complex
    * passes nuclear envelope and stim/inhib gene expression
  2. Lipid-insoluble - E.g. catecholamines
    - Hydrophilic-exert their effects on surface receptors
    - Normally no carrier proteins->short half-file
    - IC signaling mediated by IC “secondmessengers”
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2
Q
  1. Classification of hormones, the dynamics of the receptor ligand interaction, the feedback mechanism:
    Dynamics of the ligand-receptor mechanism
A

•In vitro:
-Interaction bw. hormone and receptor is governed by physicochemical laws
-Scatchard analysis: characterized the dynamics of binding reactions bw. small molecules and proteins.
•His theory can be applied to any biological system, where a substance (ligand) binds to a large-molecular binding site (receptor).
•The stronger the ligand-receptor connection is, the more non-labeled hormone is required to displace the radioactive hormone from the receptor.
•Two characteristic values:
1. Bmax: number of the total binding sites.
2. Kd: dissociation constant of the binding site
•In vivo:
-We introduce a radio-labeled hormone into the circulation and examine the dynamics of the appearance, staying, and removal of this hormone in organs as a function of time.

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3
Q
  1. Classification of hormones, the dynamics of the receptor ligand interaction, the feedback mechanism:
    The feedback mechanism
A

•When the central facilitation is inhib. by the incr. prod. of hormones, the hormone production will be inhib. by the conc. of hormones in the system.
•Low conc. of hormones will elicit prod., while high conc. will inhibit prod.
•Long, short and ultra-short feedback:
-Long feedback: from periphery to hypothalamus
-Short feedback: from periphery to pituitary gland
-Ultra-short feedback: bw. hypothalamus and pituitary gland

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4
Q
  1. Communication among cells, intracellular receptor signaling: Communication among cells
A
  • Hypothalamus: most important organ in cell signalling regulation; because of its central integrating role.
  • Intracellular communication:
    1. Direct comm.: Transp. substances via gap junctions.
  • Ionic transp. bw. cytoplasm of one cell to another (requires cells to be close)
    2. Contact comm.: Info. processing by molecules integrated in cell memb.
  • Typical method in immune system (requires cells to be close).
    3. Comm. by secretion: Secr. molecules bw. cells that are not so close.
  • Important for function of immune and nervous system.
  • Secretion can be endocrine, paracrine, autocrine or neurotransmitted secretion.
    4. Cytoskeletal comm.: Processing mechanical info. that will influence the cell by cytoskeletal system
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5
Q
  1. Communication among cells, intracellular receptor signaling: type of communicating secretion
A
  • Endocrine secretion: specialized cells will secrete hormones that will reach the recipient cells through the bloodstream.
  • Paracrine secretion: bw nearby cells, local chem. mediators will be broken down, immobilized or taken up by cells close to the producer - very quickly
  • Autocrine secretion: when the cells own signal will affect it. A type of paracrine effect.
  • Neurotransmitted secretion: a synaptic transmission causes the cells to secrete neurotransmitters. Can be found in the CNS and in ANS
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6
Q
  1. Communication among cells, intracellular receptor signaling: intracellular receptor signaling
A
  1. Lipophilic hormones can pass the cellular membrane and bind to cytoplasmic receptors
  2. Then they reach the nucleus and exert the effect.
  3. The receptor–ligand complex is able to enter the nucleus, and the DNA-binding domain of receptor “finds” DNA segments, called HRE`s.
  4. Then it activates the structure gene downstream to HRE and a biological response is initiated trough a protein(enzyme)
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7
Q
  1. Membrane receptor signalling
A

-Receptor: may be a special transmembrane protein of 3 parts:
1.Ligand binding part (on EC side)
2.Central part (passes through membrane)
3.Inner part (on IC side)
-Nicotinic Acetylcholine Receptor:
•Ion-channel forming a transmembrane protein
•Found in CNS & PNS
•In closed state before binding of ACh
*Binding of ACh->conformational changes->opening of cation channel
*Influx of cations->local excitatory pot. & stim. of AP
*Channel returns to closed state after dissociation of ligand
-Glutamate-sensitive receptors:
•Post-synaptic membrane-integrated cation channels
•3 main groups according to glutamate antagonists
1.NMDA receptor (N-metyl-D-aspartate)
*Binding of Mg2+->receptor closed
*Mg2+ dissociation->receptor activated
2.AMPA receptor
3.Kainate receptor
-Anion Receptors:
•Opening of anion channels, important in inhibitory synapses of CNS
•2 main mediators:
1. GABA: acts on GABA-A (ionotropic) or GABA-B (metabotropic) receptors.
2.GABA-B decreases IC cAMP & effects K+ channels.

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8
Q
  1. Hypothalamic releasing and inhibiting factors: Hypothalamus
A

•The highest cerebral integrator of autonomic functions, and it synchronizes neural and hormonal activity.
•Hormones in parvocellular area go to adenohypophysis
-Consist of supraoptic nucleus and paraventricular nucleus
-Secrete oxytocin, vasopressin, TRH, CRH and neurotensin
-The neurosecretion go down the axon, reach portal circ. of pituitary stalk of median eminence and then reaches anterior lobe of pituitary gland.
-Releases hormones into the vascular system.
•Hormones in magnocellular area go to neurohypophysis
-Consist of ventromedial, dorsomedial and infundibular nucleus
-Contains liberin or statin
-Secrete oxytocin-prod. cells and vasopressin-prod. cells
-The neurosecretion goes down inside axon from site of prod. to site of release.

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9
Q
  1. Hypothalamic releasing and inhibiting factors
A

•Hypophysotropic: h. prod. in hypothalamus
•TRH: thyrotropin releasing h. Stim. thyroid gland h.
•CRF: corticotropin releasing f. Adrenocorticotropin stim. hormone. Facilitates synt. of ACTH, MSH and opiates, also splitting POMC.
•GnRH: gonadotropin releasing h. Facilitates synt. of FSH and LH.
•GRF: growth h. releasing f.
•GIH: growth h. inhib. h.
•PRF: prolactin releasing f. Responsible for lactation, and ovulation in rat.
•MRF: melanocyte releasing f. Activator of MSH. Inhib. factors are dopamine, somatostatin, GABA and VIP.
•PIF: Prolactine inhib. f. (dopamine)
•VIP: Vasopressing inhib. protein. Incr. synt. and secr. of prolactine and other anterior pituitary h. Acts neg. on synt. of somatostatin
-Angiotensine 2: a sep. h. in hypothalamus, but also prod. in periphery.
•Acts on hypothalamus and pituitary gland. Stim. synt. and release of somatotropin and prolactin.

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10
Q
  1. Adenohypophysis, the synthesis and release of ACTH: Adenohypophysis
A
-Anterior lobe of hypophysis
•Endocrine gland found in Rathke’s pouch
-Developed from entodermal glandular tissue during embryonic life. 
•Hormones: 
-TSH, ACTH, FSH and LH: act only on endocrine glands -
 are glandotropic. 
-PRL and STH: are histotropic
*TSH: thyroid stimulating hormone
*ACTH: adrenocorticotropic hormone
*FSH: follicle stimulating hormone
*LH: luteinising hormone
*PRL: prolactin		
*STH: growth hormone (somatotropin)
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11
Q
  1. Adenohypophysis, the synthesis and release of ACTH: Synthesis and release of ACTH
A

•The brown area (central part) of adenohypophysis prod. ACTH.
•Derived from Pre-POMC, and is therefore involved in the adaptive processes of the organism.
•ACTH helps to mobilize energy reserves and decr. pain sensation during stress.
-Regulated by feedback principle; long and ultra-short
•Long: incr. glucocorticoid conc. Glucocorticoid prod. is stim. by ACTH, and will elicit at neg. feedback on ACTH synt.
•Ultra-short: ACTH inhib. CRF. Neural impulses reaching hypothalamus are integrated by CRF synt. cells. The release of CRF is pulsatile and its circadian fluctuation determines synt. and secr. of ACTH.

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12
Q
  1. Growth hormone: general about growth hormones
A

•Normal growth maintained by continuously high levels of STH (somatotropin), and pulsatile incr. and decr. of STH.
•STH: prod. in acidophil cells of adenohypophysis.
-Both short and long duration fluctuation.
-Synt. by effect of GRH and GIF
•Gigantism: Incr. secr. during young age
•Acromegaly: Incr. secr. during adult life, bone growth and asymmetrical growth of limbs
•Dwarfism: Decr. secr. during young life

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13
Q
  1. Growth hormone: Effects and regulation
A

-Effects on protein metabolism: STH incr. uptake of aa. in cells -> incr. IC protein synt. -> incr. growth
•Directly stim. by free aa. in plasma
-Effects on lipid metabolism: start lipolysis -> stim. GNG.
•High STH conc: stim. conversion of FA into acetic a.
• = STH mobilises E stores to cover E needs of protein synt.
-Effects on carbohydrate metabolism: STH inhibit insulin-facilitated glu uptake in adipose tissue -> incr. plasma glu level -> incr GNG
•STH also stim. prod- of glucagon.
*Too much STH: pathological hyperglycemia, because STH have an antiinsuline-like and glucagon agonist effect.
-Indirect effects of STH:
•IGF (insulin-like growth factors) influence bone, cartilage and CT: stim. bone formation, bone growth and acromegaly in adults
-Regulation of STH secretion:
•Low glu level and decr. level of arginine in plasma will stim. STH secr.
•Synt. and release will be stim/inhib by plasma hypothalamic factors according to the actual needs. These adjustments will be done by endogenous hypothalamic signals.

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14
Q
  1. Hormones from the neurohypophysis: Neurohypophysis
A

•Posterior lobe of hypophysis - extension of hypothalamus

  • Developed from ectodermal nervous tissue during embryonic life.
  • Oxytocin and vasopressin: hormones prod. in hypothalamus, but stored and secr. from neurohypophysis.
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15
Q
  1. Hormones from the neurohypophysis
A

-Oxytocin:
•Stim. uterus, especially during late pregnancy and birth.
•During birth oxytocin helps keep the strength of labour contractions.
•You can give oxytocin to “activate” labour.
•The prod. of oxytocin will also be stim. by breastfeeding of the baby.
-Vasopressin:
•Functions on kidneys, helps regulate the loss of water by regulating uptake of water from urine. This will also help reduce the level of urine.
•Dehydration will be very stim. for vasopressin, because of the huge need for water abs. and storage.
•If the vasopressin secr. were to be inhib., the amount of urine would be doubled almost 10 times.

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16
Q
  1. MSH and the Pinneal gland: MSH
A

•Melanocyte stim. hormones
•Mostly known effect of this hormone family is stim. of pigment granule prod. and transp. along the microtubule system in pigment cells: resulting in the decoloration of cells
-Alpha MSH: formed from ACTH
-Beta MSH: formed by beta lipotropin
-Gamma MSH: cleaved from N-terminal of POMC.
-Effect of MSH on pigment cells:
•From nucleus of pigment cells to periphery there is a microtubule system arranged in a radial symmetry. In resting state, pigment granules are located around nucleus.
•MSH exerts migration of pigment granules along the microtubule matrix system, which is a process connected to activation of motoproteins.
•The pigment is evenly distributed in the cell, and the cell or tissue becomes darkened.
•MSH also facilitates pigment synthesis.

17
Q
  1. MSH and the Pinneal gland: Pinneal gland
A
•Located caudo-dorsally from hypothalamus and composed of pinealocytes and glial cells. 
•Synt. serotonin and melatonin
-Melatonin prod. has a circadian rhythm which depends on light exposure; darkness acts pos, while strong illumination (daytime) acts neg
-Serotonin prod. starts in light
-First step of melatonin synt. is transformation of serotonin to N-acetylserotonin by NAT
-Function of melatonin:
•Skin: opposite to MSH: induces conc. of pigment granules -> skin becomes pale
•In mammals, 3 important effects:
1.Sexual function
-inhib. sexual maturation (humans)
-inhib. GnRH-FSH-LH axis
-human ovulation
-incr. sexual cycle in cat and horse
-decr. sexual cycle in sheep and goat
2.Psychic effects
-incr. depression, appetite, sleepiness
-jet lag
3.Defence against free radicals
18
Q
  1. The thyroid hormones: The thyroid
A

•Develops during early embryonic life; because thyroid hormones can´t get through the placenta.
•Prod. metabolites into the bloodstream and iodine containing hormones.
•Hormones: thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and calcitonin.
-Important for metamorphosis-normal development, reg. of intermediary metabolism and homeothermy-stabile thermogenesis.
*Facilitate carb. metabolism, incr. lipid metabolism and stim. protein metabolism.
*Also have a neuronal and a cardiovascular effect
*Calcitonin has an effect on bone metabolism
-Defects:
1.Hypothyroidism: deficiency of thyroid h.
*Young: dwarfism and slow sexual development.
*Adult: loss of hair/fur, slow reflexes, low/none reproductive abilities
2.Hyperthyroidism: overproduction of thyroid h. Same effects in adult and young; incr. BMR and O2 consumption, weight loss and incr. irritability.
3.Goiter: Enlargement of thyroid gland, also called struma. Often occurs at the same time as hyper or hypothyroidism.

19
Q
  1. The thyroid hormones: Synthesis
A

-Thyroglobulin will be degr. by follicular cells to hormones (T4, T3 and rT3)->ready for entering circ. Every step but the release is facilitated by TSH hormone.
Steps:
1.Iodine enters the gland by active pumps
2.By the help of lysosomal peroxidase enzyme the iodine will be converted into atomic iodine.
3.The atomic iodine makes monoiodotyrosine (MIT) consisting of 1iodine or diiodotyrosine (DIT) consisting of 2iodine. The MIT or DIT will then bind to TG. 2DIT will make one T4, while 1DIT + 1MIT will make either one T3 or rT3.
4.Epithelial cells synt. colloid TG, for the purpose of storing hormones.
5.Endocytosis of TG will be the first step of hormone release
6.Only T4 and T3 get into bloodstream, while other proteins will be degr. IC.
7. T4 and T3 will be secr. at basal side of cells by help of passive diffusion.

20
Q
  1. The thyroid hormones: Regulation
A
  • Controlled by feedback regulation, both long and short.
  • Long feedback is under the effect of TRH synt, while short is under effect of TSH synt. Both long and short feedback reg. are inhib. by T3.
  • T3 is mostly derived from T4 (T4 becomes T3 in the tissue).
  • T4 is reg. by exogenous and endogenous factors.
  • Exogenous factors: photoperiod, feeding, temp., stress and pharmacons (drugs).
  • Endogenous factors: genetic determination, physiological state, changes of hormone receptors and tacivation ability of peripheral cells.
21
Q
  1. Synthesis, regulation and physiological effects of glucocorticoids: Glucocorticoids
A

•Prod. in adrenal cortex, and belongs to steroids.
•3 zones of adrenal cortex:
1. Zona glomerulosa/zona arcuata
2. Zona fasciculata
3. Zona reticularis
•Glucocorticoids are prod. in zona fasciculata, but also some prod. in zona reticularis.
•Most important glucocorticoids: Cortisol and corticosterone
-Rat, rabbit and pigeon: corticosterone dom.
-Cattle and dog: the hormones occur in equal conc..
-Sheep, pig and human: cortisol is important

22
Q
  1. Synthesis, regulation and physiological effects of glucocorticoids: Regulation
A
  • Hypothalamic–pituitary (CRF – ACTH) control is the basis of reg.
  • Prod. in zona reticularis is less dependent on ACTH.
  • The roles of glucocorticoids are determined by long feedback loop.
23
Q
  1. Synthesis, regulation and physiological effects of glucocorticoids: Physiological effects
A

•Long lasting mobilization of energy reserves of the body.
•Metabolism:
-carbohydrate metabolism: hyperglycemia
-protein metabolism: protein catabolism
-lipid metabolism: cleaving of fats, redistribution
•Other physio. effects: Circulatory, blood cell, lymphoid, nervous system
-Defects: Glucocorticoid insufficiency: Na+ loss, oligemia, K+ increase (cardiac weakness), edema in capillaries, muscular weakness.

24
Q
  1. Pharmacological effect of glucocorticoids
A

•Utilized in veterinary practice because of their excessive antiinflammatory effect.
•Effects of continuous high level of glucocorticoids: on mesenchymal cells, Antiphlogistic effect and Antiallergic effect
-Effect on medenchymal cells:
•Inhib. of proliferation of mesenchymal cells:
*Fibroblast and collagen formation is inhib., cicatrisation is considerably prolonged.
*Normal granulation and total healing of wounds are inhib.
*Osteolysis is remarkable: osseous matrix is degr., Ca is mobilized and excreted and, in the end, osteoporosis develops.
-Antifphlogiatic (anti-inflam) effect:
•Due to the phospholipase A2 blocking effect of glucocorticoids
*decr. inflam. color, dolor and tumor
*decr. basophil degranulation (decr. allergic reactions)
*Masking effect: since corticoid treatment only decreases inflam. symptoms, it is not meant to be a causal treatment
-Antiallergenic effect:
•Significantly inhib. histamine release
•Do not have a direct influence on Ag-AB reaction

25
Q
  1. Physiology of stress
A

•Organisms are exposed to constant environmental effects.
•To maintain internal environment, organism avoids stimuli that would shift the equilibrium.
•If the stim. is very strong or disturb internal equilibrium state (“noxious stimulus), defence mechanisms are put into force
•Specific response: a possibility of defence.
-E.g. AB response to a virus infection.
•Nonspecific response: In case of noxious stimuli, when specific response is not available.
-The organism’s reaction is nonspecific i.e., the same to every stimulus - called stress-reaction. This form of adaptation is called “general adaptation syndrome (GAS)”
-Stressors: Leads to development of GAS
*Phys. stimuli: mech. stimuli, surgical intervention, limitation of motion, temp., radioation, weather, etc.
*Specific pathogens: virus, bact., parasites, etc.
*Related to feeding: deficiencies; vitamins, micro elements, intoxications
*Emotional stimuli: physic stress, pain, lack of stimuli

26
Q
  1. Pharmacological effect of glucocorticoids, physiology of stress: Phases of stress
A

4 phases of stress response:

  1. Initial stage: During stress, release of ACTH starts immediately.
    - Often accompanied by Cannon’s alarm reaction.
    - The effect of catecholamines declines within a few min., but ACTH level remains high.
  2. Stage of resistance: Adrenal cortex prod. high amount of glucocorticoids. As a result unnecessary functions are rapidly reduced to the minim. Functioning of immune system becomes inhib., storing processes are terminated.
    - Because of excessive glyconeogenesis, hyperglycemia is persisting, but does not elicit insulin secr.
    - Energy needs of the body are covered by burning fat
    - Able to resist effects of stressor for a longer period.
    - If the noxious effect persists, there are two possibilities:
  3. Stage of exhaustion: Energy reserves expire, stage of collapse starts and the animal dies.
  4. Stage of adaptive disorders: E.g. arthritis, chronic hypertension, ulcer and hepatic failure, etc.
27
Q
  1. mineralocorticoids
A

•Class of corticosteroids (steroid hormones)
•Influence salt and water balances
•Primary mineralocorticoid is aldosterone
*Synt in adrenal cortex, in glomerular zone, where aldolase enzyme is found
*regulate electrolyte and water metabolism by acting mainly on DCT
*main effect is reabs. of Na+ and secr. of K+
-Overdose:
•Isosmotic hypervolemia because of the reabs. of Na+ and H2O.
•Renal escape can occur, due to rising BP.
•Lack of K+, which lead to muscular weakness and in worst cases alkalosis
-Deficiency:
•Acidosis will occur.
•High K+ conc. will damage the cardiac functions which will cause an IC hypervolemia.
•The above together with the loss of Na+ and H2O due to vomiting and diarrhea will cause oligemia and hemoconc. Will again cause less uptake of O2, which will lead to cardiac failure.
-After cardiac failure, azotemia will occur and death will soon follow.

28
Q
  1. mineralocorticoids: Regulation
A

Long feedback

  1. Incr. of plasma K+ conc. is the most important regulator->will lead to rapid reactive ability.
  2. Renin-Angiotensin system will be activated when juxtaglomerular apparatus detects Na+ deficiency. First angiotensin II, then aldosterone will be synt.
  3. Decr. of Na+ content in the body activates synt. of mineralocorticoids->will be a part of volume regulation.
  4. ACTH has a mainly tolerant effect. In case of ACTH deficiency, zona glomerulosa becomes thinner by 50%, but aldosterone synt. is not terminated.
29
Q
  1. Catecholamines
A

•Adrenal medullar hormones
•Stored in granules
•Released to EC space by exocytosis
-Includes epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine
•Epinephrine/adrenaline: Prod. by effects of muscle activity, cold, decr. BP
*‘Fight’ hormone
•Norepinephrine/noradrenaline: of aggressive behaviour. Prod. by effects of hypoxia, pain, emotional anxiety
-Receptors:
•2 alpha and 3 beta receptor subtypes.
-Alpha subtypes have further subtypes.
•Norepinephrine stim. mainly alpha1 and beta1 receptors.
•Epinephrine stim. mainly beta2 receptors, but also acts on alpha1 receptors.
•Dopamine acts on D1 and D2 receptors
1.Alpha receptor effects:
•alpha-1: SM contraction, GGL, sympathetic synaptic transduction
•alpha-2: regulation of transmitter release in CNS
2. Beta receptor effects:
•beta-1: stim. of heart and adipose cells
•beta-2: SM relaxation and incr. metabolism

30
Q
  1. Cathecholamines: Synthesis
A
  1. Precursors enter granules.
  2. The first key enzyme is DBH present in granules. Result is granular norepinephrine.
  3. Then it is passively released into cytoplasm, where it is converted to epinephrine by PNMT.
    - The two main products are stored in granules until liberation.
  4. Chromogranin contains stored final products: E, NE, and also special peptides. These modulators are released from adrenal gland and other sympathetic terminals, and effectively influence sympathetic effects. The phenomenon is called peptidergic co-transmission.
31
Q
  1. Cathecholamines: Effects
A

-On circulation:
-Similar to effects of sympathetic NS
-Sympathetic activation:
*Low epinephrine: beta effect dom.->dilation of BV’s, CO incr.
*High epinephrine: alpha effect dom. Vasoconstriction & incr. BP
*High norepinephrine: similar to high epinephrine. Stronger contractions of SM (few beta 2 receptors)
•Effect depends on plasma conc. of hormone, receptor types and ratio of receptor types
-On Intermediary Metabolism:
•Mobilize rapidly utilizable energy sources
•Incr. BMR and O2 cons.
-Facilitation of hepatic GGL, elevated resp. freq., high performance of heart
-Calorigenic effect
•Carb metabolism
-Elevates blood glu. Initiates GGL in liver and muscle cells
-Shifts carb stores from liver to muscle
•Lipid metabolism
-FFA levels incr. Beta receptor effect dom. in adipose tissue
-Incr. utilization of fat in adipose

32
Q
  1. Insulin and glucagon: Insulin
A

-Prod. by pancreas (B cells)
-Anabolic storage processes. Stim. glu->gly conversion in cells (for storage)
•21 + 31 aa. Dimer (if Zn present): A chain, B chain+Zn
•Synt. as pre-pro-insulin->C peptide cleaved at release
•Low species specificity
•Biphasic secretion. 10 min half life.
•Stim. of anabolic & storage processes
Insulin receptors:
-7 subtypes of receptors
-No. 4 most significant: muscle
Effects of insulin:
-Regulates glu intake.
-Insulin dep. tissues: Vital tissues (Brain, blood cells, brain capillaries, liver, muscle and adipose)
*GLUT 1, 2 & 3 receptors.
-Insulin independent tissues: Muscle, adipose tissue
•Metabolic effects: Effects indep. of glu uptake. Acts on all cells of body->incr. storage and anabolic processes
*Incr. gly, protein & fat synthesis
*Decr. degr. speed of precursors->inhib. enzymes of gly, protein & fat catabolism
*Incr. glu utilization in liver and adipose
-Insulin deficiency:
•Cells unable to take up glu
•Elevated plasma glu->reabs. capacity of renal tubules is lost->glu in urine
•Type I: Juvenile. Insulin-sensitive
•Type II: Adult. Insulin-insensitive
•Type III: Adult. Insulin-sensitive

33
Q
  1. Insulin and glucagon: Glucagon
A

-Prod. by pancreas (A cells)
-Mobilizes hepatic gly stores.
-Elevates plasma glu conc. redistribution of carb stores from liver to muscle
•29 aa.
•Intestinal & pancreatic origin
•Low species specificity
•5 min half-life
•Acts only in liver->incr. plasma glu conc., decr. gly synth., stim. GNG
Effects:
-Antagonist of insulin.
-Acts only in liver

34
Q
  1. Insulin and glucagon: Regulation
A

1.Delicate regulatory system->amplifies secr. of particular hormones, decr. incidental overprod.
•Paracrine Activity Regulation
-Release of insulin by B cells->hyperglycemia->influence glucagon synt.
-Low plasma glu->direct stim. for glucagon secretion->direct stim. of B cell secr. & D cells-inhib. overprod.
-Somatostatin->influence hormone prod. of A & B cells. Decr. PP secr. of F cells
2.Glucose & aa. levels of plasma
-Plasma glucose and aa. circulating in pancreas
*High levels->insulin
*Low levels->glucagon
-Feed-forward mechanism: Glucagon and other peptides stim. insulin synt.
*Glu loss and glucose salvage
3.Neural regulation
-Synt. of insulin and glucagon under control of autonomic NS
*Sympathetic effects: beta receptors
*Parasympathetic effects: ACh receptors

35
Q
  1. Insulin and glucagon: Effects on Intermediary Metabolism
A
1.Carbohydrate metabolism
•Incorporates aa. into proteins (GNG)
•Glu level decr.
2.Lipid metabolism
•Incr. triglyceride synth
•Decr. lipid degr.
•FA synt. from AcCoA
3. Protein metabolism
•Stim. aa. uptake (except hepatocytes)
•Enhanced protein synt.
•Decr. protein degr.
•Positive nitrogen balance
36
Q
  1. Eicosanoids
A

-Autocoids: Eicosanoid and peptides.
-Eicosanoid: Prod. everywhere in body, by all cells
•Lipid soluble
•Quickly degraded
•Act locally/paracrine effect
1.Incr. inflam.-Prostaglandins and leukotrienes initiate inflam.
2.Insulin release-HPETE stim. PGE2->inhibits insulin release by B cells
3.Bone reabs.–PGE2 has PTH-like effect->incr. Ca2+ permeability on osseous interstitial side->Ca2+ enters plasma
4.Reprod.–Precondition of luteolysis is PGF2-alpha prod.
5.Thrombocytes–Enothelial cells release PGI and NO->induce G protein mediated incr. of cAMP. IC cAMP inhib. PLA2 enzyme->no thromboxane->no platelet aggregation. TXA2 synt. in platelets incr.->incr. aggregation.
6.Kidney–Prostacyclin in renal tubule cells enhance renin secretion->incr. RPF->antagonist of AD
-Synthesis:
•20-C FA’s. Controlled synth. from phospholipids via enzymatic steps
•Mediated by G protein->activates PLA2 enzyme
•HPETE, Lipoxins, HETE, leukotrienes
-Regulation:
•Corticosteroids and mepacrine inhib. eicosanoid synth (anti-inflammatory effect of glucocorticoids)
•Salicylic acid, indomethacin and Iboprufen inhib. cyclooxygenase.
•Benzenediamine and imidazole inhib. thromboxane synthase. (decr. platelet aggregation)