glucose, Ca, & GH Flashcards

Question

bone formation steps

Answer 1

1. ossification: production of osteoid (bone matrix) by osteoblasts & osteocytes (matrix ~35% of bone mass) 2. calcification: mineralization of the osteoid by deposition of hydroxyapatite crystals (hydroxyapatite is ~65% of bone mass) - all bones form by ossification followed by calcification

Answer 2

- uninucleated - **deposits matrix** - secretes collagen & osteocalcin - **osteogenesis**: form new bone & mineralize it - **produce ODF & OPG that regulate osteoclast maturation, activation, & activity** - ODF = osteoclast differentiation factor (aka RANKL) → activates osteoclasts - OPG = osteoprotegerin → protects bone & serves as regulator for ODF: caps ODF so no longer can stimulate osteoclast - have receptors for PTH & vit D3 - secrete OPG but PTH inhibits

Answer 3

- multinucleated - degrades matrix - release of Ca & P - osteolysis: bone breakdown & demineralization (resorption) of mature bone - have receptors for calcitonin - bone resorption occurs at surface - activity dependent on factors produced by osteoblasts (ODF & OPG)

Answer 4

- mature osteoblast - embedded in matrix as it builds around osteoblasts - no longer produces proteins to build matrix - part of bone structure

Answer 5

- fibers of collagen type I - other collagens - osteocalcin & other proteins (~10%) - protein matrix: collagen & osteocalcin (~35% of bone mass) - hydroxyapatite (bone mineral) Ca10(PO4)6OH2 (~65% of bone mass)

Answer 6

PTH binding to osteoblasts stimulates production of ODF - ODF binds to receptor in inactive osteoclast progenitor cells & stimulates: - ↑ maturation - ↑ proliferation - ↑ activity

Answer 7

1. **abundant lysozymes & tight jx** 2. **secretes cathepsin K (Ca solubilization)** 3. **express proton pumps to create acidic envir in the resorptive pit**

Answer 8

1. osteoclast **podosomes create adhesion** to bone surface - creates **resorptive pit** → microenvironment to digest bone & keep area under cell isolated from area not under cell - **anchors** osteoclast & creates **seal** 2. **ruffled border** increase SA for absorption 3. expression of **anion exchangers** that exchange bicarbonate for Cl- which is released into resorptive pit through Cl- channels in ruffled border 4. carbonic anhydrase (CA) catalyzes rxn to **↑H+** pumped through **ATPases** in ruffled border into resorptive pit 5. released into resorptive pit - citric acid - cathepsin K (CaK) = proteolytic enzyme - HCL 6. effective release of collagen & minerals through basolateral membrane

Answer 9

- stimulates osteocalcin & type I collagen genes in osteoblasts → ↑ bone matrix - **inhibits synthesis of PTH** - high levels of vit D = low levels of PTH - vit D wants to deposit Ca in bone, not activate osteoclasts to digest bone like PTH

Answer 10

- estrogen & GH stimulate OPG - OPG binds ODF & prevents its binding & activation of osteoclasts - results in a ↓ rate of bone resorption - estrogen & GH both decrease w/age - estrogen stimulates OPG in osteoblasts - GH stimulates growth & OPG

Answer 11

ovariectomy = removing ovaries - decreasing OPG - levels of estrogen decrease - bone volume decreases over time - osteoclast # & activity increases over time - supplementing w/ estrogen maintains constant bone volume

Answer 12

porous bone - bone resorption > bone deposition - normal process of aging but can be aggravated by other things - decreased bone mineral density (BMD) - decreased overall bone mass - increased skeletal fragility

Answer 13

soft bone caused by decreased mineral:matrix ratio - bone is there but minerals are not → bone is not as strong or healthy - commonly due to calcium/vit D deficiency - aka rickets in developing bones before closure of epiphyseal plate - rickets can cause bone deformities

Answer 14

**T3** stimulates osteoblasts to ↑ bone matrix - ↑ collagen type I & other collagens - ↑ non-collagen proteins (osteocalcin)

Answer 15

**cortisol** inhibits osteoblast production of bone matrix

Answer 16

- produced by somatotroph cells in anterior pituitary gland - pulsatile secretion pattern - GHRH regulates synthesis & secretion of GH - ⊕ inhibitor - Arc nucleus - somatostatin regulates secretion of GH (⊖ inhibitor) - not much influence on synthesis - Arc nucleus

Answer 17

used to ↑ milk production in cattle

Answer 18

stimulatory: - gonadal steroids - TH inhibitory - cortisol - somatostatin - IFG-1 in liver (main target of GH)

Answer 19

- detected early on in fetus - organ growth, development, fetal growth - peaks at 12w during fetal development - lowest level during childhood during early years

Answer 20

- significant effect on postnatal growth & bone maturation - stimulates: 1. GH secretion from somatotrophs 2. hypertrophic chondrocyte differentiation (bone growth) 3. bone mineralization & **angiogenesis**

Answer 21

- stimulate GH secretion from somatotrophs - accelerates growth during puberty

Answer 22

- closure of epiphyseal plate & cessation of growth mediated by E2 - abundant E2 = sooner closure (females)

Answer 23

- inhibits: - GH secretion from somatotrophs - GHR expression in chrondroblasts - (IGF-1 expression in chondrocytes) - stimulates: somatostatin → inhibits GH secretion

Answer 24

GH uses a cytokine receptor - through membrane 1x - made of dimer - extracellular & intracellular parts of receptor - **JAKS** proteins associated w/ intracellular receptor → first to become phosphorylated - activated receptors recruit nearby proteins called **STATs** - STATS become activated & dissociate to translocate to nucleus - acts via regulation of gene expression - metabolic regulators: - IFG-1 - IGFBPs - signal transducers: STATS - DNA repair genes - main form of action: translocating STAT proteins to nucleus to bind to DNA & stimulate txn/tsl of genes - intracellular signalling pathway - GH signaling activates other downstream mol/pathways but details are less well understood

Answer 25

- GH effects **independent** of IGF-1 - more directed towards catabolism - no IGF-1 produced in liver → no ⊖ feedback effect on pituitary GH ∴ high GH

Answer 26

- **liver** - muscle - adipose tissue - kidney - heart - bone (epiphyseal plate)

Answer 27

- GH effects mediated by IGF-1 - more directed towards anabolism - IGF-1 produced in liver will have ⊖ feedback effect on pituitary

Answer 28

stimulates proliferating & hypertrophic zones - result of local production of IGF-1 & also IGF-1 production in liver

Answer 29

stimulates resting zone

Answer 30

**estrogen + androgens** stimulate GH to stimulate resting zone **estrogens alone** inhibits resting zone ➞ early closure of epiphyseal plate

Answer 31

**cortisol** inhibits: - GHR expression in chondroblasts of resting zone - IGF-1R expression in chondrocytes of hypertrophic zone

Answer 32

- growth plate/epiphyseal plate = site of bone elongation - **resting zone** → chondroblasts that express GHR → respond to GH & stimulate cells to express & respond to IGF-1 as they move into the proliferating & hypertrophic zones - **proliferating zone** → chondroblasts - express IGF-1R ➞ respond to local IGF-1 - **hypertrophic zone** → chondrocytes - express IGF-1R ➞ respond to local IGF-1 - **ossification zone** → mature chondrocytes

Answer 33

- **chondroblasts** = progenitor cells (stem cells) in resting zone → express GHR - **GH stimulates chondroblasts → stimulates IGF-1 to ↑ proliferating hypertrophic zones** - bone length will be dictated by activity of chondroblasts & chondrocytes in proliferating & hypertrophic zones - density will be dictated by osteoblast activity (bone matrix deposition)

Answer 34

stimulates hypertrophic & ossification zones

Answer 35

- prepubertal growth is similar in males & females - females reach puberty sooner than males - closure of epiphyseal plate is more strongly regulated by estrogen ∴ it happens more quickly in females

Answer 36

- hypersecretion of GH - typically from pituitary tumors - **gigantism** occurs before closure of epiphyseal plates - **acromegaly** occurs after closure of epiphyseal plates - associated w/ abnormal growth of other organs - e.g. cardiomegaly & cardiac insufficiency

Answer 37

- hypoglycemic hormone: goal is to ↓ BG - preproinsulin ➞ proinsulin ➞ insulin - protein hormone ∴ originates from gene txn & tsl in β cells: - proinsulin is packaged in secretory granules in the golgi apparatus - formation of disulfide bonds & cleavage happen in secretory granules - both insulin & C-peptide are released when stimulated - in order to fold insulin properly you need: 1. disulfide bonds → connect ⍺ & β chains 2. cleave C-peptide (connecting peptide) - happening as these mol are being stored in secretory vesicles → equimolar ratios of C-peptide & insulin

Answer 38

- hyperglycemic hormone: goal is to ↑ BG - product of cleaving proglucagon - cleavage of proglucagon in ⍺ cells gives glucagon - cleavage of proglucagon in intestinal L-cells gives GLP-1 ➞ ↑ insulin synthesis & release

Answer 39

- somatostatin goal: to **regulate release of glucagon & insulin** - somatostatin-28: pancreatic **δ cells → potent at inhibiting glucagon secretion** - somatostatin-14: **CNS & hypothalamus → potent at inhibiting GH secretion**

Answer 40

- basal: insulin secreted in fasting state - stimulated: in response to exogenous stimuli (e.g. meal → ↑ BG) - carbohydrates = main stimulant - glucose is the most potent stimulator of insulin release - insulin levels in blood begin to rise ~10-15 min after a meal - insulin levels raise ~100x & peak around 30-45 min after a meal - insulin levels will return to basal level ~90-120 min after a meal → glucose tolerance test: assesses fx of endocrine pancreas ability to release insulin

Answer 41

biphasic response: 1. initial spike in insulin with ↑ glucose levels 2. insulin levels ↓ but slowly rise again when BG still ↑

Answer 42

- glucose channels - GLUT1 & GLUT3 - found in all tissues - very high affinity for glucose - basal glucose uptake - GLUT2 - hepatic, intestinal, renal tubular cells - medium affinity for glucose - glucose uptake when glycemic levels are high (postprandially) - GLUT4 - skeletal muscle & adipose tissue - dependent on insulin signaling to become activated & transport glucose (insulin-dependent) - activated by exercise in skeletal muscle cells (mediated by AMPK) - targets of insulin

Answer 43

- isoenzyme of hexokinase - **converts glucose → glucose 6-P** - **catalyzes first step in glycolysis pathway** - lower affinity for glucose than hexokinase - not inhibited by G6P - expressed in β cell of pancreas - method of ATP production for insulin release

Answer 44

- glucose enters cell via GLUT 1/2/3 channels (independent of insulin) - glucokinase converts glucose ➞ G6P - high levels of G6P **do not** inhibit glucokinase - glycolysis,TCA cycle, & resp chain produce ATP - ↑ ATP → closes K channels → depolarization of cell membrane → opening of Ca channels - mediate by Ca signaling (not GPCR) - Ca signaling releases insulin via exocytosis

Answer 45

- glucose (hyperglycemia) → main stimulant - PSNS stimulus (ACh)

Answer 46

- incretin family: GLP-1, gastrin, CCK - incretin effect: “boost” in insulin release from pancreas in response to glucose ingestion (but not when glucose is injected IV) - maximum peak of insulin release when ingested - **↑ response of β cell to produce more insulin** - GLP-1: glucagon-like peptide 1 - CCK: cholecystokinin - help close K channels

Answer 47

- hypoglycemia - sustained hyperglycemia - ⍺2-adrenergic receptors

Answer 48

1. closes more K channels → faster more efficient depolarization 2. more Ca influx → stronger effect 3. ↑ insulin transcription

Answer 49

receptor tyrosine kinase (RTK) 1. binding of insulin to extracellular portion stimulates autophosphorylation of tyrosines on intracellular portion of receptor → **intrinsic kinase activity** - binding connects dimer 2. autophosphorylation of tyrosines stimulate recruitment of **IRS1/2** (= insulin response elements 1 & 2) 3. IRS1/2 recruits **PI3K** (phosphatidylinositol 3 kinase) → catalyzes conversion of PIP2 in membrane to PIP3 → activates PKB - several different type of pathways insulin can effect

Answer 50

- glycogen synthesis: PKB inhibits GSK3 (glycogen synthase kinase 3) ∴ activates glycogen synthase - protein synthesis - stimulates glucose uptake: activation of PKB to transport GLUT4 channels to membrane

Answer 51

1. stimulates glucose uptake 2. stimulates glycogenesis 2. stimulates protein synthesis 3. inhibits glycogenolysis

Answer 52

1. stimulates glucose uptake 2. stimulates glycogenesis 3. stimulates protein synthesis 4. inhibits glycogenolysis

Answer 53

1. stimulates glucose uptake 2. stimulates glycerol synthesis 3. stimulates triglyceride formation & storage

Answer 54

- first target: ⍺ cells → inhibits glucagon release - somatostatin from δ cells also inhibit glucagon secretion - also stimulates insulin secretion - released by most of same stimuli that promote insulin secretion

Answer 55

1. stimulates glycogenolysis 2. stimulates gluconeogenesis 3. stimulates ketogenesis = ketone body production from fatty acids

Answer 56

PKA stimulates: 1. glucose 6-phosphatase 2. PEPCK 3. glycogen phosphorylase PKA inhibits: 1. glycogen synthase 2. pyruvate kinase

Answer 57

transcription of G6P, PEPCK, & glycogen phosphorylase

Answer 58

- ↑ carbs stimulate **insulin** but **not** glucagon - ↑ proteins stimulate glucagon release → AA are more potent stimulators of glucagon than insulin in the absence of hyperglycemia - body thinks there is no glucose ∴ fasting state

Answer 59

1. eating carbs 2. gluconeogenesis 3. glycogenolysis

Answer 60

- glucosuria - osmotic diuresis → high glucose in filtrate brings water & electrolytes out of body - first compartment of water mobilization: extracellular space (interstitial — intravascular) - ↓ ECF V & ↑ osmolarity → activate SNS - EPI ↑ glycogenolysis, lipolysis, gluconeogenesis, & glucagon secretion → ↑ BG even more - dehydration in intracellular space - untreated results in coma (extreme SNS impairment) & hypovolemic shock - dehydration due to osmotic forces ↓ GFR & activates RAA system & AVP release → ↑ BP (AT2) & cannot efficiently reabsorb necessary water & Na - glucose should not be in filtrate - ion/water reabsorption based on osmotic gradient - more concentrated urine (because of more glucose) = ↑ water loss - polyuria/polydipsia - dehydration - ↑ RAA system & vasopressin

Answer 61

inappropriately ↑ circulating BG (hyperglycemia)

Answer 62

defective insulin secretion

Answer 63

defective insulin action

Answer 64

when body cannot make enough insulin during pregnancy - insulin resistance: body of pregnant female is not responding to insulin effectively ∴ not uptaking glucose into cells so that glucose is in blood & available to be transferred to the fetus

Answer 65

cells use insulin less efficiently

Answer 66

insulin insufficiency - aka insulin-dependent - low/absent blood insulin levels - typically affects young indiv - causes: genetic, autoimmune - absence or destruction of β cells = inability to produce insulin - tx: insulin replacement

Answer 67

insulin resistance - aka insulin-independent - low, normal, or high insulin levels - typically affects adults (increasing in younger indiv) - causes: genetic, obesity, lifestyle - loss of sensitivity of peripheral tissues to insulin - can also present destruction of β cells - problem is response to insulin - tx: multifactorial

Answer 68

complication of DM when BG is high but glucose is not getting into cells resulting in fatty acid breakdown & excessive ketone body production by the liver - more common in T1DM - liver produces ketone bodies as alternative energy source thinking that body is starving (no glucose in tissues)

Answer 69

AMPK (adenosine monophosphate protein kinase) - activated by low ATP levels in **myocyte** - ↑ glucose uptake via **GLUT4 channels** in an insulin-independent mechanism

Answer 70

- **diabetic ketoacidosis**: high BG but low glucose in cells → lipolysis → built up ketone bodies in the liver - **cardiovascular disease**: DM causes vasculopathies (disease of the blood vessels) that can result in myocardial infarction, atherosclerosis, & other complications - **myocardial infarction** = heart attack - **atherosclerosis** = closing of arteries - even before DM is detected, hyperglycemia causes damage to vasculature & abnormal bf → microvascular damage - ~50% of P with DM (T2DM more commonly) have hypertension or another form of CVD - DM ↑ risk of coronary heart disease, myocardial infarction, & hypertension - relationship is multifactorial including effects of insulin signaling, genetic causes, & presence of obesity & dyslipidemia - **dyslipidemia** = the imbalance of lipids such as cholesterol, low-density lipoprotein cholesterol, (LDL-C), triglycerides, and high-density lipoprotein (HDL) - abnormal lipid metabolism - metabolic syndrome: hypertension, dyslipidemia, diabetes

Answer 71

- **fasting BG test** measures BG after overnight fast - < 99mg/dL = normal - > 100 mg/dL indicates pre-diabetes or diabetes - **glucose tolerance test** measures BG clearance as a measure of insulin function 1. take fasting blood sample 2. drink glucose-rich liquid 3. take second sample 1-2h later → glucose levels should be back to basal levels in 2h - **A1C** test detects glycated hemoglobin: blood protein that is associated w/ glucose - measures the level of BG over time (2-3 mo) - important for screening pre-diabetics

Answer 72

1. in liver: 1. stimulates gluconeogenesis via glucose-6-phosphatase & PEPCK 2. stimulates glycogen synthase 3. inhibits glycogen phosphorylase 1. in adipose tissue 1. activates HSL to break down fatty acids 2. inhibits glucose uptake 1. in muscle 1. ↓ protein synthesis 2. stimulates myostatin to break down muscle 3. inhibits glucose uptake 1. inhibitory effects on immune system (blocks phospholipase A) 2. enhances epinephrine activity 3. stimulates PNMT conversion of NE → EPI 4. stimulates production of lung surfactant → maturation of lungs in fetal tissues 5. stimulates dopamine (inhibitory signal for PRL) & also inhibits PRL directly 6. promotes lactation at parturition 7. inhibits osteoblast production of bone matrix 8. inhibits GH 1. GH secretion from somatotrophs 2. GHR expression in chondroblasts 3. IGF-1R expression in chondrocytes 4. stimulates somatostatin → inhibits GH secretion

Answer 73

1. fight or flight 2. stimulates gluconeogenesis 3. inhibits immune system 4. hepatic glycogenolysis ➞ stimulates glycogen phosphorylase to release glycogen 5. inhibits glycogen synthase 6. stimulates HSL to ↑ lipolysis 7. ↑ HR & SV 8. peripheral vasoconstriction 9. ↑ BP 10. dilation of coronary arteries 11. dilation of muscle vessels

Answer 74

1. fetal development: sensory systems (auditory/visual), neurogenesis, neural transmission 2. metabolism 1. stimulates protein expression & turnover 2. ↑ metabolism due to thermogenesis 3. stimulates expression of β-adrenergic receptors & G-proteins to enhance actions of EPI 4. **enhances O2 absorption by resp system** 5. **↑ expression of erythropoietin to enhance production of RBCs** 6. **enhances β-adrenergic receptor-mediated effects in the heart** (inotropic/chronotropic effects) 7. **↑ GI motility tract** 8. **↑ GI absorption efficiency** 9. **stimulate lipolysis** 10. **↑ appetite** (CNS satiety/hunger centers) 1. non-shivering thermogenesis via UCP-1 redirecting the proton flow from the H+ ATPase (final step of the respiratory chain) → dissipating energy in the form of heat instead of ATP generation in BAT 2. stimulates GH: 1. GH secretion from somatotrophs 2. stimulates hypertrophic & ossification zones of epiphyseal plate 3. bone mineralization & angiogenesis 1. **T3** stimulates osteoblasts to ↑ bone matrix: ↑ collagen type I, other collagens, & non-collagen proteins (osteocalcin)

Answer 75

- stimulates Na reabsorption in collecting duct - facilitates transcription of Na/K ATPase pumps in basolateral membrane → pumps Na back into blood & K into cell - stimulates **Sgk1 to inactivate Nedd4-2 channels** → inactivated Nedd4-2 channels cannot destroy ENaC (Na channels) ∴ Na can re-enter cell via apical membrane - ↑ urine **excretion of K**: stimulates expression of K channels in apical membrane of principal cells of collecting duct

Answer 76

1. ↑ transcription of P450aldo →↑ aldosterone production 2. vasoconstriction → ↑ BP → ↑ renal bf 3. promote release of AVP from PVN → ↑ water reabsorption 4. release EPI & NE from adrenal medulla → enhance activity of SNS & NE release in nerve terminals

Answer 77

- vasodilation, hyperfiltration, & natriuresis: Na excretion - counterbalances effects of renin-angiotensin-aldosterone system - ↑ GFR - inhibits Na & water reabsorption in principal cells of collecting duct - inhibits secretion of renin, aldosterone, AVP, & ACTH

Answer 78

1. glycogen 2. ACTH & cortisol 4. epinephrine 5. ghrelin 6. TNF-⍺

Answer 79

1. stimulates glycogenolysis (stimulates glycogen phosphorylase & inhibits glycogen synthase) 2. stimulates gluconeogenesis (G6P & PEPCK) 3. stimulates ketogenesis

Answer 80

1. stimulates epinephrine 2. stimulates gluconeogenesis (glucose-6-phosphatase & PEPCK) 3. activates hormone sensitive lipase (HSL)→ breaks down fatty acids 4. inhibits glucose uptake 5. ↓ protein synthesis 6. stimulates myostatin to break down muscle fibers

Answer 81

1. stimulates HSL to ↑ lipolysis 2. inhibits glycogen synthase 3. stimulates glycogen phosphorylase 4. stimulates gluconeogenesis

Answer 82

activates AgRP & NPY neurons to secrete AgRP & NPY to stimulate appetite

Answer 83

1. inactivates insulin receptor → inhibiting activity of IRS1/2 2. ↓ insulin sensitivity in adipocytes 3. inhibits lipoprotein lipase ➞ inhibits lipogenesis 4. stimulation of lipolysis

Answer 84

1. insulin 2. leptin 3. incretins 4. somatostatin 5. prolactin

Answer 85

1. stimulates glycogenesis 2. stimulates protein synthesis 3. inhibits glycogenolysis 4. stimulates glucose uptake 5. stimulates glycogen synthase (PKB inhibits GSK3 which inactivates glycogen synthase ∴ activates glycogen synthase) 6. stimulates triglyceride formation & storage 7. inhibits glucagon release from ⍺ cells 8. stimulates POMC neurons to secrete ⍺-MSH & inhibits AgRP & NPY neurons → suppresses appetite

Answer 86

1. stimulates POMC neurons to secrete ⍺-MSH & inhibits AgRP & NPY neurons → suppresses appetite 2. enhances insulin sensitivity in liver & muscle: enhanced IR activity & inhibition of gluconeogenesis

Answer 87

↑ response of β cell to produce more insulin → ↑ insulin synthesis & release

Answer 88

stimulates insulin release & inhibits glucagon release

Answer 89

stimulates insulin synthesis & β cell proliferation

glucose, Ca, & GH Flashcards

(113 cards)