Hormones 2 Flashcards
What is the function of the small intestine?
- digest and absorb nutrients
- glucose, amino acids, and triacylglycerols are absorbed from the intestine into the blood stream to reach each cell
What is different about RBC from other cells?
- no organelles, nucleus
- concave shape
- only uses glucose, needs consistent supply
What does the brain use for energy?
- ketone bodies (preference)
- glucose (uses most of the time)
What nutrients does the heart/skeletal muscle use for energy?
- less specific
- fatty acids
- ketone bodies
- lactate, alanine
- glucose
- muscle can store glycogen
What does adipose tissue store? usage?
- triacylglycerol, stores for energy
- when glycogen storage has filled up, extra energy is stored as fat
- two way path for fatty acids and glycerol into and out of adipose tissue by beta oxidation
- one way for glucose
Role of liver in metabolism?
- stores glucose as glycogen
- breaks down glycogen into glucose
- stores fatty acids as triacylglycerols, releases them by beta oxidation
- glycolysis (lactate)
- gluconeogenesis (lactate)
- releases ketone bodies
- brings in glycerol, fatty acid synthesis
- VLDL
Pancreas Anatomy? Functions? (4)
- under liver, behind stomach, above small intestine
- Head
- Neck
- Body
- Tail
- Uncinate
- Exocrine (95%)- release enzymes for digestion
- Endocrine-islet of langerhans have beta cells for secretion of insulin, alpha cells secrete glucagon
Exocrine functions of pancreas? enzymes?
- synthesize and secrete digestive enzymes/zymogens
- trypsinogen
- chymotrypsinogen
- pancreatic lipase- digest lipids
- amylase
Endocrine functions of pancreas? hormones?
- synthesize and secrete hormones, formed by the islets of langerhans
- insulin (beta cells- found in core)
- glucagon (alpha cells-located in periphery)
- gastrin and somatostatin (delta cells)
- pancreatic polypeptide (F cells)- inhibits somatostatin
What composes the core of the islets of langerhans in the pancreas? mantle? (6)
- core- beta cells that produce insulin
- mantle- outer shell, contains alpha, delta, and F cells
- alpha cells produce glucagon
Precursors of insulin? C peptide? (7)
preproinsulin gene -> proinsulin -> insulin
- connecting peptide (C peptide) is cut off by two digestive enzymes
- C peptide is secreted together with insulin
- usually 1:1 ratio with insulin
- use it to measure amount of insulin b/c insulin get used
- insulin is conserved peptide
Steps of insulin synthesis and secretion in beta cells? (8)
- DNA transcription in nucleus produces mRNA for preproinsulin production
- transported to cytosol where translation begins from N terminal (leader sequence) to C terminal
- transported to rough ER where translation finishes of preproinsulin, leader sequence is cleaved by signal peptidase to form proinsulin
- packaged in Golgi, removes C peptide, convert proinsulin to insulin, insulin and c peptide packaged together and released into blood
- Calcium and glucose are the signal
- degradation of C peptide is slower - Secretory granules (condensation and storage)
Steps of the signal that regulates insulin secretion and synthesis? (9)
- increased glucose levels in blood
- glucose is transported by GLUT 2 into beta cells
- glucose catabolism by glycolysis to generate ATP and pyruvate
- ATP/ADP ratio increases to shut off potassium (K+) channel, depolarizing membrane
- force open calcium channel, 2nd signal, calcium moves into cell (influx)
- calcium signal squeezes sacks containing insulin and C peptide into bloodstream, and also for regulation of the calcium activated insulin gene expression via CREB leading to transcription activation of insulin gene to produce more insulin
- insulin is water soluble so it doesn’t need a carrier protein to travel in blood stream
What is the role of glucose transporter 2 (GLUT 2)?
glucose absorption in liver and pancreas
Insulin signaling path in the muscle and adipose tissue? (10)
- increased insulin binds to insulin receptors on outside of cell, insulin receptor is heavily glycosylated tetramer consisting of two subunits (alpha2beta2), beta subunit has tyrosine kinase activity in cytoplasm
- inner side of receptor is autophosphorylated, activated
- other molecules (IRS) become phosphorylated, leading to translocation of GLUT 4
- GLUT 4 normally located in cell, when insulin is present it moves to cell membrane - glucose comes into cell by GLUT 4
- in muscle, glycolysis happens in order to create energy to do work
- extra glucose is stored as glycogen
- still extra, glucose turns into pyruvate to synthesize fatty acids and stored in adipose tissue
Effects of insulin on liver? (11)
- increased glycolysis
- decreased gluconeogenesis
- increased glycogen synthesis
- decreased glycogenolysis
- increased fatty acid synthesis
Why doesn’t glucose uptake occur in liver but does in adipose and skeletal muscle?
liver uses GLUT 2 (not regulated by insulin) but adipose and skeletal uses GLUT 4 which is regulated by insulin
effects of insulin on adipose tissue?
- increased glucose uptake
- increased glycolysis
- decreased lipolysis
effects of insulin on skeletal muscle?
- increased glucose uptake
- increased glycolysis
- increased glycogen synthesis
- decreased glycogenolysis
- increased protein synthesis
Biochemical and physiological effects of insulin?
- enhance anabolism, inhibit catabolism
- insulin is a growth hormone
Where is glucagon synthesized and secreted? precursors?
-alpha cells in pancreas when blood glucose levels are low
preproglucagon gene -> proglucagon -> glucagon
-mature glucagon is a single chain polypeptide of 29 amino acids
What inhibits glucagon?
insulin and glucose
- inverse relationship between glucagon and insulin
- low glucose = high glucagon
- low insulin = high glucagon
What increases glucagon secretion?
- amino acids (Arginine, Alanine, GABA)
- catecholamines (epinephrine)
- glucocorticoids (GI hormones)
- nervous system
- high levels of circulating FFA
Target of glucagon?
liver for glucose metabolism
Glucagon signal transduction? (16)
- water soluble so it cannot penetrate membrane
1. glucagon binds to receptor on cell surface, form complex
2. G protein subunits bind the receptor
3. adenylate cyclase interacts with G proteins to form an active complex with the alpha subunit
4. ATP is used to turn adenylate cyclase-alpha into cAMP
5. cAMP interacts with protein kinase A (repressor group releases from catalyzing groups)
6. protein kinase A is active leading to phosphorylation of many substrates (some active, some inactive) hormone amplifies: - 1 hormone leads to 20 G proteins activated
-> 100 cAMP -> 100-1000 phosphorylation -> net effect is 10^5 or 10^6
-hormonal function is very sensitive
How many binding sites for cAMP does protein kinase A have? (17)
4
What can stop the glucagon signal? (17)
- receptor for glucagon can turn GDP into GTP
- Adenylate Cyclase converts ATP to cAMP
- phosphodiesterase can break down cAMP into AMP to stop the signal
glucagon effects on blood glucose levels? (18)
- low glucose
- increased glucagon
- increased cAMP
- increased PKA
- different enzymes then lead to different pathways to increase glucose levels
Glycogen synthase pathway? (19)
low glucose levels
- increased glucagon
- binds glucagon receptor
- increased cAMP
- increased PKA
- increased phosphorylation
- glycogen synthase decreases which decreases glycogen synthesis
- glycogen phosphorylase increases to increase glycogen degradation
- increased glucose
Glucagon effects on target cells? (20)
- decreased glycolysis
- increased gluconeogenesis
- decreased glycogen synthesis
- increased glycogenolysis
- decreased fatty acid synthesis
- increased fatty acid oxidation
What is the insulin/glucagon ratio after a meal? during fasting? how does this relate to glycolysis/gluconeogenesis? (21)
meal:
- increased insulin/glucagon ratio
- PFK 2 activity
- high dephosphorylation
fasting:
- decreased insulin/glucagon ratio
- F2,6P bisphosphatase activity
- phosphorylation high F2,6P activates PFK1 which increases glycolysis low F2,6P activates activates F1,6P Base which increases gluconeogenesis
Blood glucose levels in a diabetic vs normal person? (3 things) (22)
- basal level of diabetic is higher, over 100 mg/dL
- given glucose tolerance test, there is a bigger spike in the diabetic
- healthy person reaches basal levels quickly, diabetic takes a long time to reach basal levels
- diabetic doesn’t deal with glucose very efficiently
What is glucagon like peptide (GLP-1)? Functions? (23)
- comes from gut genes (small intestines)
- intestines L cells
proglucagon -> GLP-1 -C terminus of GLP-1 is modified to amide
Functions:
- targets stomach- slows down release of food (gastric emptying) for better digestion
- activates pancreas beta cells to generate insulin
- inhibits glucose release from liver
- enhance muscle glucose uptake, heart
- brain helps to stop eating
- lowers blood glucose
- increases glucose consumption
- decreases glucose generation
- decreases appetite
GLUT 1? GLUT 2? GLUT 3? GLUT 4? affinity? capacity? (24)
1- transport glucose to RBC, high affinity, low capacity, function all the time no matter blood glucose levels (low Km)
2- transport glucose to liver, low affinity, high capacity, efficient when blood glucose levels are high (high Km)
3- transport glucose to brain, high affinity, low capacity, functions all the time, when glucose is low (low Km)
4-transport glucose to adipose and muscle tissues, insulin affects glucose uptake, functions at normal range of glucose
Relationship between glucose levels and insulin during starvation? glucagon?fatty acids? ketone bodies? (25)
- high glucose= high insulin
- high glucose= low glucagon
- high glucose= low fatty acids
- high glucose= low ketone bodies
During prolonged starvation:
- insulin decreases
- glucagon increases then levels off
- fatty acids increase linearly
- ketone bodies increases exponentially
What is the steps from tyrosine to epinephrine? (28)
- tyrosine is oxidized by using the enzyme tyrosine hydroxylase and BH4 (rate limiting) to turn into DOPA
- DOPA decarboxylation by DOPA Decarboxylase to generate Dopamine
- Dopamine is oxidized by Dopamine Hydroxylase using ascorbate (vitamin C) to form norepinephrine
- Amino group is methylated to form epinephrine- vit B6, vit B12, and folate are important
- BH4 is important for each step
Epinephrine effect on liver? path? (31)
increased epinephrine
- binds to adrenergic receptor
- increases cAMP
- increases protein kinase A
- increases gluconeogenesis
- decrease glycolysis
- increases glycogenolysis
- decreases glycogenesis - increases blood glucose
- same as glucagon
Effects of epinephrine on heart and liver? (slide 32,33)
- it has opposite effects on heart vs liver
- liver: reduces F2,6P bisP, slows glycolysis
- heart: increase F2,6P bisP, increases glycolysis
What is leptin? (37)
leptin: a hormone that inhibits appetite and weight (OB gene)
- have leptin (OB) gene, normal weight
- loss of leptin (OB) gene, cannot suppress appetite, leads to obesity
- small peptide
- synthesized in adipocyte
- proportional to body fat
Weight gain vs weight loss and leptin? (38)
- weight gain = increased leptin to decrease food intake and increase energy expend
- weight loss = decrease leptin to increase food intake and decrease energy expend
- determined by setting point, can change set point, cells expand or shrink
What is the diabetes gene (DB)? (39)
- leptin receptor- membrane protein enriched in the hypothalamus
- no DB gene= no receptor, more body fat, leptin cannot bind anywhere
- with DB gene= normal, leptin can bind receptor
Parabiosis experiment? (40)
- circulatory systems of two mice are joined together
- combine OB(no leptin gene) with wild, OB gets smaller because hormones are shared from the wild, wild stays same
- combine DB(no diabetic gene- no receptor) with wild, DB didn’t change and wild got smaller because DB has no receptor but higher leptin levels because of higher body fat, wild gets smaller because it has receptors for leptin and there is a lot of leptin circulating due to the DB mouse
- combine OB (no leptin) with DB (no receptor), DB stays same size because it has no receptor, OB gets smaller because it is using the leptin from the DB
- brain regulates appetite
Exercise changes on adipocytes? (42)
- subcutaneous adipocytes from exercising mice can improve glucose homeostasis
- darker color
- increase mitochondria
- Factor X enhances glucose uptake to muscle
