Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
111 Cards in this Set
- Front
- Back
|
Different types of endocrine "glands" |
-Single cells dispersed throughout a non-endocrine organ (gastrin cells) -clusts of cells within a non-endocrine organ (pancreas) -endocrine gland dedicated completely to endocrine function (pituitary) -endocrine cells associated with meiosis and reproduction (ovaries) |
|
|
Insulin synthesis |
-synthesized as prohormone -packaged in golgi and stored in secretory vessels with zinc -C peptide is removed within vessel -Insulin and C peptide are secreted |
|
|
C peptide |
fragment released with insulin. Can be used to assess beta cell function |
|
|
Biphasic release of insulin |
Initial burst of insulin followed by a slower long lived increase |
|
|
Out of the pancreas, where does insulin reach first? |
The liver via the portal vein |
|
|
Glucose stimulated insulin secretion |
-Glucose enters beta cell thru GLUT2 -Converted to G6P -Glycolysis produces ATP -ATP binds to ATP-regulated K channel and causes depolarization -Voltage gated Ca channels open -Ca promotes insulin secretion |
|
|
GLP-1 stimulated insulin secretion |
-GLP-1 from small intestine binds to GLP-1 receptor on beta cells -Activates Gs -Increases cAMP, PKA, and Ca |
|
|
Long chain free fatty acid stimulated insulin secretion |
-Bind GPR40 -Activate Gq -Increase PKC and Ca |
|
|
Norepinephrine stimulated insulin secretion |
-Bind alpha 2 adrenergic receptor -Activate Gi -Decrease cAMP and Ca -Decrease insulin secretion |
|
|
Ach stimulated insulin secretion |
-Bind muscarinic receptor -Activate Gq -Increase Ca |
|
|
Insulin signaling pathway |
-Insulin binds and induced conformational shift -Cross-phosphorylation of cytoplasmic domaints -Recruitment and phosphorylation of IRS -PI3K recruited -PIP2 converted to PIP3 -PK1 and AKT recruited -AKT regulates protein phosphatases, FOXO1, mTORC1, and SREBP-1 Can also recruit SOS which activates Ras and MAPK cascade |
|
|
Insulin resistance |
Blocks IRS due to: -Inflammatory cytokines -increased intracellular triglycerides -Increased amino acids activate mTORC1 which negatively feeds back -Binding of SOCS3 |
|
|
mTORC1 |
Activated by insulin Promotes protein synthesis Can be activated by influx of amino acids Activates SREBP1c |
|
|
What happens when mTORC1 is high? |
Feeds back to insulin receptor and IRS to decrease insulin signaling |
|
|
SREBP1c |
Activated by insulin and AKT Enters the nucleus and upregulates gene expression in hepatocyte Upregulates glucokinase and pyruvate kinase, stimulating glycolysis Upregulates PPP Drives fatty acid synthesis |
|
|
Protein phosphatases |
Needed for glycogen synthesis, glycolysis, and entry of pyruvate into the TCA cycle |
|
|
FOXO1 |
Important during fasting Stimulates gluconeogenesis and assembly of VLDLs |
|
|
What does insulin do to FOXO1 |
Phosphorylates it and inhibits it |
|
|
What does PKC do to IRS |
Inhibits it |
|
|
How is glycogen synthase activated? |
By dephosphorylation via protein phosphatases |
|
|
How is the PPP activated? |
SREBP1c |
|
|
What does insulin do to LPL? |
Increases it |
|
|
What does insulin do to VLDL? |
Inhibits the assembly and secretion of VLDL from hepatocytes |
|
|
perilipins |
Proteins that coat and stabilize fat droplets. When phosphorylated, they release TGs from adipose stores |
|
|
Which cells do not express glucagon receptors? |
Skeletal muscle |
|
|
Primary adrenergic receptor on beta cells |
Alpha 2 |
|
|
Primary adrenergic receptor on alpha cells |
beta 2 |
|
|
PFK2 |
Activated by insulin/AKT signaling Increases F26BP Inhibits gluconeogenesis |
|
|
How is glycolysis increased in the liver during a fed state? |
Increased F26BP and PFK1 Increased pyruvate kinase (SREBP1C) Increased pyruvate dehydrogenase Decreased PEPCK |
|
|
How is triglyceride synthesis increased in the liver during a fed state? |
Excess AcCoA is converted to citrate and shuttled to the cytoplasm where is is converted back to AcCoA then to malonyl CoA and then to fatty acids |
|
|
What does malonyl CoA do? |
Inhibits beta oxidation |
|
|
What happens in the liver during the fed state? |
Increased glucokinase Increased glycogen synthase Decreased glycogen phosphorylase Increased glycolysis Increased triglyceride synthesis Decreased gluconeogenesis |
|
|
How does the liver increase glycogenolysis during fasting? |
Increased glycogen phosphorylase Decreased glycogen synthase |
|
|
How does the liver decreased glycolysis during fasting? |
Decreased pyruvate kinase Decreased F16BP and G6Pase |
|
|
How does the liver increases gluconeogenesis during fasting? |
Increased PEPCK |
|
|
How does the liver decrease lipogenesis during fasting? |
Increased malonyl CoA decarboxylase |
|
|
What happens to skeletal muscle during the fed state? |
Increase glucose uptake via GLUT4 increase glycolysis Increase glycogen synthesis Increase protein synthesis Increase lipogenesis (in extreme excess) |
|
|
What happens to adipose during the fed state? |
Increase lipoprotein lipase Increase FFA storage Increase glucose uptake via GLUT4 Decreased hormone sensitive lipase Increase protein synthesis |
|
|
What happens to adipose during fasting? |
Activation of hormone sensitive lipase Phosphorylation of perilipins to release TGs Beta oxidation of FFA Ketone bodies formed from AcCoA Loss of GLUT4 Low LPL |
|
|
What happens to skeletal muscle during fasting? |
Decreased GLUT4 and glycolysis FFAs and ketone bodies used for ATP Muscle-specific LPL releases FFAs from VLDL Gluconeogenic substrates released Muscle glycogen used during exercise |
|
|
AMP kinase |
During caloric deprivation, exercise, or activation of sirtuins, the ration of AMP to ATP increases. This activates AMP kinase which increases catabolic reactions in the cell and decreases anabolic reactions |
|
|
Autophagy |
Cells package their organelles into vaculoes that fuse with lysosomes and degrade them for ATP |
|
|
GCN2 pathway |
GCN2 senses low amino acid levels in tRNA and inhibits protein synthesis. Also stimulates amino acid synthesis and inhibits lipid synthesis |
|
|
What does AMP kinase do to mTORC1? |
Inhibits it |
|
|
Abnormal mTORC1 activation |
Mutated TSC1/2 Leads to tumors in the CNS, seizures, and mental retardation |
|
|
UPR |
When there is too much energy in a cell, too many proteins are made and not folded correctly. UPR detects the unfolded proteins and increases the expression of anti-oxidant genes and inflammatory genes to protect the cell. It also decreases protein synthesis and increases TG synthesis. If all else fails, apoptosis will be induced |
|
|
Anorexigenic peptide |
Senses when the stomach is full Ex: serotonin, alpha MSH, catecholamines, CCK, GLP-1, insulin |
|
|
Orexigenic peptide |
Senses when the stomach is empty Secreted when Ghrelin is perceived Ex: neuropeptide Y, cannabinoids |
|
|
Adiponectin |
Inversely proportional to fat mass. Inhibits food intake by increasing insulin sensitivity |
|
|
Leptin |
Encourages the use of calories so we don't increases adipose reservoir. Signals there are adequate fat stores. Secreted proportional to fat mass Stimulates angiogenesis, humoral and adaptive immunity, steroid synthesis. Decreases insulin secretion. |
|
|
Neuropeptide Y |
Stimulates food intake |
|
|
Alpha MSH |
Necessary for leptin to work since leptin does not act directly on output neurons. Inhibits food intake and stimulates ATP use |
|
|
Endocannabinoids |
Stimulate food intake and converse ATP |
|
|
Leptin deficiency results in |
Morbid obesity |
|
|
What may cause resistance to diet-induced weight loss? |
UCP protein mutation Adrenergic receptor mutation |
|
|
Parathyroid hormone |
Functions to increase plasma Ca Increases bone resorption Increases Ca reabsorption in kidney Decreases Pi reabsorption in kidney |
|
|
Activation of CaSR |
Inhibits PTH secretion Degrades newly synthesized PTH |
|
|
Vitamin D |
Stimulates Ca and Pi absorption in small intestine by upregulating TRPV5/6 and calbindin Facilitates Ca reabsorption in kidney Helps out PTH |
|
|
Synthesis of Vitamin D |
Aquired from UV radiation and the diet Hydroxylated in the liver Hydroxylated in the kidney (rate limiting step) Stimulated by PTH and inhibited by high levels of Pi Transported by vitamin D binding protein |
|
|
Vitamin D deficiency |
Causes Ca and Pi to fall and prevents proper mineralization of bone. Rickets in children and osteomalacia in adults |
|
|
Calcitonin |
Synthesized and secreted by parafollicular cells of thyroid Stimulated by high plasma Ca Inhibits bone reabsorption |
|
|
FGF-23 |
Produced by osteocytes Needs to be inhibited Excess causes an inhibition of Pi reabsorption in the kidney and inhibition of Vit D hydroxylation in the kidney. Leads to hypophosphatemia and bone wasting |
|
|
Ca transport in thick ascending limb |
Triple transporter drives Ca transcellularly Positive lumen drives Ca paracellularly CaSR on basolateral side can detect high Ca and inhibit the triple transporter |
|
|
Ca transport in collecting duct |
Ca enters thru TRPV5 and is shuttled transcellularly and exits thru Na/Ca exchanger PTH acts here to upregulate TRPV5 |
|
|
Pi transport in proximal tubules |
80% occurs here Uptake via Na/Pi symporter NPT2 and exits thru Pi/anion exchanger PTH causes apical transporter to be internalized and degraded |
|
|
PTH effects on Ca and Pi in the kidney |
Promotes Ca reabsorption in DT and TAL Inhibits Pi reabsorption in PT |
|
|
PTH or Vit D on bone |
Binds to osteoblast and activate RANKL Stimulates of osteoclast differentiation Blocked by OPG |
|
|
Formation of thyroid hormone |
Na/I symporter on thyroid follicle cells Iodide is transported to the lumen Tyrosine is iodinated by thyroid peroxidase Dual oxidase generates hydrogen peroxide Colloid droplets are internalized and hydrolyzed T3 and T4 are secreted |
|
|
Thyroid regulation |
T3 feeds back to the pituitary Pituitary can convert T4 to T3 so it can participate in the feedback Some feedback to the hypothalamus, but minimal |
|
|
What happens with high levels of T4 |
TSH is suppressed |
|
|
TSH |
Activates Gs and Gq to upregulate Na/I symporter and take up more iodide Increases dual oxidase and peroxidase Upregulation of thyroglobulin transcription Gland can become hypertrophic and hyperplastic |
|
|
What happens when intrathyroidal iodide concentrations are very high? |
Thyroid hormone synthesis and secretion is inhibited Dual oxidase and peroxidase are inhibited |
|
|
Thyroid hormone transport |
Bound to TBG, TTR, or albumin T4 binds more avidly |
|
|
T4 conversion |
T4 is a prohormone and must be converted to T3 to be used D1 in liver and kidney (supplies serum T3) D2 in brain, pituitary, brown fat (local generation) |
|
|
Euthyroid sick syndrome |
Decreased T3 or T4 seen with chronic illness even though the thyroid is working fine D1 and D2 are inhibited |
|
|
D3 |
inactivates T3 and T4 makes reverse T3 |
|
|
Actions of thyroid hormone |
Bone growth and differentiation Brain function and differentiation Beta adrenergic agonist Increases ATP use but decreases efficiency (heat production) |
|
|
How thyroid hormones generate heat |
Alter SERCA Increase Na/K ATPase pumps Promote futile cycles insert uncoupling proteins into the mito membrane |
|
|
TR alpha |
Found in brain, heart, kidney, bone Regulate growth, body temp, post-natal differentation, heart rate |
|
|
TR beta |
Found in hypothalamus, pituitary, choclea, liver Negative feedback in HPT axis Lowers cholesterol and TG |
|
|
GH signaling |
GH binds and causes receptor dimerization Bring JAK2 together Trans phosphorylation of JAK2 Docking site for STAT5b Moves to the nucleus and activates IGF-1 transcription Inhibited by SOCS |
|
|
IGF-II |
Important for both the growth of the fetus and the placenta during fetal life Paternally expressed gene |
|
|
GH in the fed state |
Amino acids promote GHRH release Promotes growth and protein anabolism Increases IGF-1 |
|
|
GH in the fasting state |
Hypoglycemia promotes GHRH release Switched fuel consumption to lipids by stimulating hormone sensitive lipase Stimultes gluconeogenesis Inhibits GLUT4 in muscle Decreased IGF-1 |
|
|
GH axis |
Hypothalamus produces GHRH Pituitary produces GH (pulsitile release) GH acts on the liver to produce IGF-1 IGF-1 feeds back to pituitary and hypothalamus Ghrelin also stimulates the hypothalamus |
|
|
Overall effect of GH |
Decrease fat mass and increase muscle mass |
|
|
IGF-1 |
Stimulated by GH Forms a ternary complex in the liver. Acts as an endocrine hormone Can act as via paracrine in the tissues directly |
|
|
PTH effect on IGF-1 |
Stimulates it |
|
|
Glucocorticoid effect on IGF-1 |
Inhibits it and slows growth |
|
|
Precocious puberty |
Early acceleration of linear growth and early closure of the growth plates. Leads to short stature |
|
|
Larson dwarfism |
Mutation in GH receptor, IGH-1 production in the liver is impaired |
|
|
Estrogen |
Promotes longitudinal bone growth and periosteal apposition Closure of growth plates at the end of puberty Maintains adult bone madd |
|
|
Adrenal medulla |
80% epinephrine 20% norepinephrine |
|
|
How is epinephrine made? |
Tyrosine (tyrosine hydroxylase) DOPA (aa decaroxylase) Dopamine (beta hydroxylase) NE (PNMT) Epi |
|
|
Secretion of epinephrine |
Sympathetic signals. Ach is released and binds to nicotinic receptors on chromaffin cells and increases tyrosine hydroxylase |
|
|
Epinephrine promotes |
glucogenolysis via beta 2 receptor. Increases blood glucose Inhibits insulin secretion via alpha 2 |
|
|
Epinephrine degradation |
MAO and COMT to metanephrine or vanillylmandelic acid and excreted in the urine |
|
|
Zona fasciculata |
Makes cortisol |
|
|
biosynthesis of cortisol |
Cholesterol (CPY11A1) pregnenolone (3BHSD) pregesterone OR (CPY17) 17-hydroxypregnenolone (CPY17) 17-hydroxyprogesterone OR (3BHSD) 17-hydroxyprogesterone (CYP21) 11-deoxycortisol (CPY11B1) cortisol |
|
|
Cortisol inactivation |
Inactivated in the liver or converted to cortisone by 11BHSD2 |
|
|
Cortisol binding |
GR receptor is bound to chaperone in the cytoplasm Binding of cortisol brings the complex to the nucleus and increases transcription |
|
|
StAR |
Transports free cholesterol into the inner mitochondrial membrane so it can get to CYP11A1 |
|
|
Physiological actions of cortisol |
-Increases gluconeogeneis -Decreases GLUT4 uptake -potentiates PNMT and catecholamine lipolysis -Increases muscle proteolysis -Increases erythropoietin synthesis -inhibits immune response -decreases reproductive axis -decreases inflammatory cytokines -decreases collagen and fibroblast proliferation -Decreases ADH -Induces Type II pneumocyte differentiation |
|
|
MC2R |
ACTH receptor on cells in zona fasciculata |
|
|
Chronically elevated cortisol |
-increased appetite -increased glycogen synthesis -decreases lipolysis -Increased TG synthesis -Truncal adiposity |
|
|
Zona reticularis |
Makes androgens (DHEAS) Appears at age 5 Contributes 50% of active androgens in women |
|
|
DHEAS biosynthesis |
Pregnenolone (CPY17) 17-hydroxypregnenolone (CPY17) DHEA (SULT2A1) DHEAS |
|
|
Regulation of DHEAS |
Regulated by ACTH Androgens don't feed back on CRH or ACTH. This loophole can give rise to congenital adrenal hyperplasia |
|
|
Zona glomerulosa |
Makes aldosterone |
|
|
Aldosterone biosythesis |
Pregnenolone (3BHSD) progesterone (CYP21B) 11-deoxycorticosterone (CYP11B2) Corticosterone (CYP11B2) Corticosterone (CYP11B2) 18-hydroxycorticosterone (CYP11B2) aldosterone |
|
|
Actions of aldosterone |
Increases Na reabsorption in the kidney and the colon Increases ENaC Increases ROMK Proinflammatory and profibrotic effects on the heart causing LV hypertrophy |
