Physio2 final pt 3

nibbs06's version from 2015-12-12 04:43


Question Answer
Cretinism is Iodine Diffiiciency
The thyroid follicles produce the Thyroid Hormones
The colloid forms & stores TGB(made in colloid) & w/in the TGB, you have stored Thyroid Hormones
Which G-Protein is used for the TSH receptors? & What's the mechanism? G(s); the alpha-subunit is bound by GTP and it stimulates AC, which converts ATP into cAMP. cAMP then causes activation of A.Kinase(PKA).
What is secreted from the C-Cells?Calcitonin is secreted from the Parafollicular Cells (C-Cells)
Which enzyme converts T4 into T3? De-Iodinase
Reverse-T3 is made by Incorrect cleavage of an Iodine from T4, by De-Iodinase
What are the reactants & products in making T3/T4(qty not important)? Reactants are Tyrosine & I2, the Products are T3(or T4) + Alanine
Explain the uptake of iodine into & out of the thyroid follicular cell Iodide(I-) is taken up via a Na/I- Symporter(NIS) on the basal side of the cell; simultaneously, Tyrosine is picked up from the blood and brought into the cell. The enzyme Thyro-Peroxidase converts Iodide, into Iodine(I2) & then I2 is moved to the Colloid(apical side) via the Pendrin-Iodo Transporter.
Which 1pt mutation is the cause of nearly 50% of children being born blind? Pendrin-Iodo Transporter Mutation (Pendrin Syndrome)
Na/I is found in the thyroid and in the _________ Alveolar Epithelial Cells of the Mammory Gland (Lacto-Peroxidase is the I- to I2 converting enzyme)
How is mono-iodotyrosin(MIT) & Di-iodotyrosin(DIT) made? & how do they differ? Tyrosine + Peroxidase will form eithr MIT or DIT based on the number of I2 used; MIT has an Iodine on the 3' position while the DIT has two iodines, one on the 3' & the other on the 5'
Explain the mechanism of synthesis for TGB? 2 peptide chains are formed in the ER, from 2 different mRNA/Genes, & then they move to the golgi to become glycosylated and di-sulfide bonds connect them together.
Iodination of TGB & Conjugation occurs (location in cell & site of TGB) On the apical side of the cell, the 2 chains are the primary site of iodination; if you have 2 iodinations occuring, then you have Di-Iodo-Tyrosyl Residue. Once you have iodination occuring, you have a lot of MIT's & DIT's around and that's when conjugation occurs(also within the peptide chains)
Explain the mechanism from when the thyroid gland is stimulated Iodinated-TGB(or colloid cell( is endocytosed into the follicular cell & is met by Lysosomes that digests TGB to release T3 & T4 into circulation. Left over MIT & DIT get De-Iodinated by Thyroid De-Iodinase to release I2 & AA, which is recycled to synthesize more thyroid hormone.
Explain the thyroid hormone synthesis-mechanism from TGB synthesis up to the organification of I2 TGB's synth from Tyr.(in Follicular Cell), packaged(vesicle) & moved to the lumen. I- enters from blood via Na/I- Symporter & meets Thyro-Peroxidase to become I2, which also moves into the lumen where it meets/reacts w/ the Tyr.-residues of TGB to form DIT & MIT
Explain the 2 possible coupling mechanism of MIT & DIT on TGB While MIT & DIT are attached to TGB, we can get 2 coupling reactions, either 2 DIT molecules combine to form T4 or we can get 1DIT + 1MIT to form T3. The Iodinated-TGB is stored in the lumen until the thyroid gland is stimulated to secrete the horm the hormones.
What is the major product when T4 reacts with De-Iodinase? More Reverse-T3 is made(45% rT4) instead of Active-T3(35%) & 20% is destroyed.
Most of the thyroid hormones in plasma are (transportation) Bound up by plasma-proteins, which can be Albumin, Pre-Albumin & Thyroxin Biding Globulin, a special protein made by the liver.
Is thyroid hormone bound by a plasma-protein in circulation, or is it in a free-form? Both! 99.5% is bound & 0.5% is in its free-form.
What has a larger half-life, T3 or T4? T4's half-life is 6 days, while T3's is 1-3 days.
How do tadpoles turn into frogs? Thyroid Hormone is responsible for their metamorphosis (PRL inhibits)
What will be the effects on growth in two people, one with a T3 Deficiency & the other with xs-T3, relative to a normal person? & what are the major differences between the two conditions? Both will be shorter than the normal person because an optimal amount of T3 is required for growth; the only differences in growth between the two is that, in T3-deficiency(cretinism/dwarfism), the epiphysis remains open & it closes in the xs-T3 person.
Thyroid conditions that cause permanent retardation is due to T3 Deficiency in Children (Cretinism) during the first 3 months of life
Hyperthyroidism effect the bodies energy stores(Net Changes in Glucose/FFA/AA), in that it Increases the rate of both Glycogenesis & Glycogenolysis(no net change in glycogen stores), Increased rate of Gluconeogenesis, Lipogenesis & Lipolysis(Net Depletion of fat stores), & Increased Cholesterol Synthesis & Degradation(Net Decrease in Plasma Cholesterol)
What is Myxedema? The accumulation of Mucopoly-Saccharide in the skin due to T3-Deficiency
What is the cause of Graves Disease & what deformaty is it associated with? An autoimmune disease causing Hyperthyroidism due to the production of TSI and it's associated with Exophthalmos(protrusion of eyeballs)
Which physiological functions require optimal T3 levels? Lactation, digestion, kidney function, cardiovascular function, reproduction(xs can cause infertility)
T3/T4 feedback to the Anterior Pituitary to inhibit TSH production by downregulating TRH-Receptors
Large amounts of dietary Iodine consumption causes Transient (2-4day) Inhibition of T4 & T4 Secretion; Wolff-Chaikoffe Effect
What test is used for Thyroid Function? There's many, but mainly RIA's
A goiter can be caused by Normal Thyroid Hormone Secretion, Hyperthyroidism(Graves Disease) & Hypothyroidism(Dietary Iodide Deficiency, Cretinism)
Causes of Hyperthyroidism can be (3) Graves Disease, Tumor of Thyroid Gland & Tumor of Pituitary Gland
Causes of Hypothyroidism can be (3) Poor Thyroid Development, Thyroid Insensitive to TSH (no goiter formed) & Hashimoto's Disease
What is Hashimoto's Disease? An autoimmune disease that causes antibodies to attack TGB, resulting in the breakdown of thyroid tissue


Question Answer
What are the names/locations of the insulin-stimulated glucose transporters? GLUT-4 in Adipose Tissue & Skeletal Muscle Tissue
During the fasted state, where does the majority of the glucose come from & what is the main hormone that's present during caloric-deficit? Liver(95%); Glucagon
What does insulin do to the glucose produced by the liver? It supresses it & causes most of it to go to Sk. Muscle & Fat
What process does insulin secretion inhibit? Inhibits Hepato-Glucose Synthesis (decreases glucagon secretion)
The cells that make up the majority of the pancreas, are Acinar Cells
What's the significance of where the alpha/beta/delta cells are found in an islet cell? Since blood flows out from the center, the cell with the most inhibitory effect(D-Cell;somatostatin) is in the middle so it can inhibit the secretion of alpha or beta cells. D-cells are the next closest to the center, they can inhibit insulin secretion from the B-cells, which are near the ridge of the islet.
With a very short half-life, how can we figure out how much insulin is being secreted by a patients pancreas? Measure the amount of biologically-inactive C-peptide that was cleaved from the preinsulin molecule & still present in the plasma.
What hormones stimulate(2) & inhibit(1) insulin secretion? Growth Hormone & Incretins(GLP1 & GIP) stimulates while Somatostatin inhibits
What neurotransmitters stimulate(1) & inhibit(2) insulin secretion? ACh stimulates, while NorEpi & Epi inhibit insulin secretion
The insulin in the 1st Phase Insulin Secretion is(relative location) stored in granules that are right in front of the insulin-granules
What's the 1st phase of insulin secretion?(name/description & how insulin's stimulated) Cephalic Phase; is the perception of food & insulin's stimulated ACh on B-Cells via Parasymp. Regulation
What's the 2nd phase of insulin secretion?(name/description & how insulin's stimulated) Early Postprandial Phase; right after food-ingestion, but before nutrients reach the blood, & insulin's stimulated via the gut-incretins (GLP1 & GIP).
What's the 3rd phase of insulin secretion?(name/description & how insulin's stimulated) Postprandial Phase; when the meal-nutrients reach the blood & insulin stimulation is due to elevated blood glucose.
Explain the neural Regulation of insulin secretion during exercise? Sympathetic Nervous System inhibits insulin secretion via alpha-adrenergic signaling (Epi & NorE)
Where is GLP1 produced & what is its purpose? L-Cells (they line the gut) & respond to glucose in gut (lumen); higher [insulin] when glucose is administered orally (vs intravenously) because GLP1 stimulating/binding to beta-cells
Explain the postprandial effects of insulin, mediated by GLP1 GLP1 is secreted by endocrine L-Cells & it binds to its B-Cell-GLP1 Receptor making the pancreas more responsive to insulin secretion & inhibiting glucagon secretion.
What is happening at the level of the tissue when GLP1 is produced/released and what's the net effect on [glucose]? Increased Insulin secretion causes increased glucose deposition in adipose & skeletal muscle, which combines with decreased glucagon synthesis, to give a total decrease in Hepatic Glucose Output & that effect, with the effect on adipose/muscle, gives a total decrease in plasma glucose.
Explain the relationship between [Glucose] & the B-Cell glucose-transporter. GLUT-2; is NOT insulin-responsive. Glucose moves in via facilitated diffusion; high-[Gluc] post-prandial is the primary reason for insulin-secretion from B-Cells.
How can we get exocytosis of insulin secreting secretory vesicles from b-cells?(4 ways) Facilitated Diffusion of Glucose via GLUT-2 causes glycolysis & increasein [ATP], which decreases K+ efflux by its channel inactivation leading to the depolarization that opens voltage-Calcium channels for Calcium influx that will cause calcium-induced-calcium release from ER to exocytose insulin. ACh from PNS-neuron can cause cause ER calcium release via IP3 stimulation(PLC's used). GLP1 uses PKC &DAG to exocytose & GIP uses PKA via AC & cAMP pathway
The cAMP pathway for hormonal release is regulated by(4; 2 stimulatory & 2 inhibitory) Beta-Adrenergic Agonist & Glucagon both using G(s) to stimulate AC to cause exocytosis but alpha-adrenergic and somatostatin both use G(i) to inhibit this process.
Name & explain the 2 diabetes theraputic innerventions that aid in insulin secretion? The use of GLP1 & Sulfonylurea(older method) to block K+ Channel to depolarize memb; making the ATP more effective since the Inulin:Glucose ratio increases.
What's the effect of Insulin & Glucagon on their respective cells? Glucagon stimulates insulin secretion & insulin inhibits glucagon secretion.
What's the effects of insulin on amino-acids & vice-versa? Insulin increases AA-uptake. AA's stimulate insulin-release(AA's are Insulin-Secretagogues)
What's the main effect of insulin on adipose tissue? & on muscle? Lipogenesis; Glycogen synthesis & AA-uptake
Explain how the insulin receptor works Insulin-R is a Tyrosine Kinase Receptor. Insulin binds to the cytosine-rich extracellular(alpha) binding-domain causing conformational change, activating intracellular-Tyrosine-Kinase (beta subunit) to begin auto-phosphorylation of proteins, like IRS, on their Tyr-residues of proteins; IRS-PO4 becomes a docking station for other proteins that have a high affinity for PO4-Tyr's, like PI3K
Explain how insulin-signaling pathway works to increase glucose-storage Insulin binds to TK-Insulin-R which autophophorylates itself & IRS-Protein, which combines with PIP2 to activate PI-3,4,5-P3 and that activates PDK, which will phosphoryalate mTOR & PKB(Akt). PKB will stimulate the influx of glucose via GLUT-4 receptor when it's phosphorylated & it wil activate Glycogen Synthase (via inhibiting the inactivation-kinase) to increase Glycogen Production.
GLUT-4 is activated by Akt protein will phosphorylate proteins in the intracelllular vesicles that are holding GLUT-4, and causes it to insert itself into the membrane.
What is PEPCK & what's it's function? The rate-limiting step in gluconeogenesis. It aids in restoring [glucose] when it's low; stimulated by glucagon secretion.
What's the difference between Hormone Sensitive Lipase(HSL) & Lipoprotein Lipase? HSL is inactive when insulin is high(post-parandial) & it is active when the body needs FFA's, which it gets by hydrolyzing TG. LPL is active when insulin is high, it's secreted into the circulatory system to convert VLDL (& Chylomicron) into FFA's that get absorbed into adipose and converted into TG, and if there's xs, then it's further converted into lipid-droplets. (Both takes something & forms FFA's from it)
Cleavage of pro-Glucagon, can form which 2 hormones? If cleavage is in alpha-cells, Glucagon. If cleavage is in L-Cells, GLP1
Which stimulate & which inhibit glucagon secretion (Glucose, FFA's, AA, Symp-system, Para-symp system, GLP1 & Cortisol) Glucose, FFA & GLP1 inhibit, while AA, SNS, PNS & Cortisol stimulate.
What are the primary and secondary effects of glucagon on the 3 major tissues of the body? Primary effect is to stimulate the release of glucose from the liver & the secondary effects are to stimulate AA-uptake(since they can be used for glucose production) & it will release FFA's from adipose-TG's.
Insulin & Glucagon are both secreted when Protein rich meal is consumed; the AA's are absorbed by the liver and turned into AA, due to glucagon presence, the AA turns into glucose and that begins to get dumped into the blood, which would begin to increase [glucose], but it doesn't get to, because insulin is being co-secreted to increase glucose uptake into skeletal muscle and fat
Which form of diabetes is an auto-immune disease? Type 1
What's the difference between insulin-resistance & glucose-intolerent, in type 2 diabetes? IR is when more insulin is initiatlly needed to bring glucose back down & GI is when the [glucose] shoots up higher than normal and elevated insulin has no effect(GI usually occurs after IR, due to beta-cell dysfunction)
What is post-pyrandial insulinemia? It's the second-stage of Type 2 diabetes (pre-diabetes; NO PATHOLOGY). It is just a state at which more insulin is required than normal to decrease glucose concentration.
Pancreatic alpha & beta cell exhaustion is when your cells are completely obliterated & at this point the patient is considered to be diabetic