Section 6 Whole Body Metabolism Flashcards
Smallest store of fuel:
carbohydrates
Largest store of fuel:
fats
In which state, fed or fasted, does glucagon dominate?
fasted
3 processes upregulated in the fasted state, when glucagon dominates:
Glycogenolysis, Gluconeogenesis, Ketogenesis
What 4 processes are up regulated when insulin dominates in the fed state?
glucose oxidation, glycogen synthesis, fat synthesis, proteins synthesis
What cells secrete glucagon?
alpha cells
What cells secrete SS?
D cells
What cells secrete insulin?
beta cells (insulin is a super hormone)
alpha, beta and D cells are all part of the endocrine/exocrine system.
endocrine
True or False? Decreased plasma glucose will up regulate beta cells of the pancreas.
F. down regulate
What pancreatic cells will upregulate the production of glucose?
alpha cells
What will up regulate the alpha cells of the pancreas?
decreased plasma glucose
What will down regulate the alpha cells of the pancreas?
increased plasma glucose
Prolonged ___ leads to the production of ketones.
hypoglycemia
Name 4 compounds that travel from the muscle to the adipose tissue:
lactate, pyruvate, amino acids, fatty acids
Structure of insulin receptor:
2 alpha chains 2 beta chains, all chains with N terminals facing outside of cell
Which domain of the insulin receptor is in the cell?
tyrosine kinase domain
Unique feature of the ligand binding domain:
cysteine rich domain closer to the N terminal side
How are the alpha and beta chains of the insulin receptor linked?
disulfide bonds
Insulin receptor substrates (IRS) phosphorylation of enzymes leads to:
glucose transport, protein synthesis, fat synthesis, glucose synthesis, and growth and gene expression
Insulin receptors are aka:
IGF-1 receptors
Which channels are open and which are closed during insulin secretion?
open: glucose and Ca++ both in, closed: ATP + K+ channel
Which glucose receptors is involved in insulin secretion?
GLUT2
What negatively feeds back to the beta cells of the pancreas?
decreased plasma glucose
Counter regulatory hormones:
glucagon, cortisol, epinephrine, norepinephrine, human growth hormone
Which is the largest energy store in grams?
carbohydrates, then fat, then proteins
location of carbohydrate storage:
liver, ECF
Location of protein storage:
muscle
Locatin of fat storage:
fat, liver
Which takes up a larger percentage of total body weight,
fat, then proteins, then carbohydrates
Largest to smallest turnover of daily energy stores:
carbohydrates, proteins, fat
energy storage for the brain:
there is none
Is the brain insulin dependent or independent?
independent
What will muscles use when glucose levels are low?
free fatty acids and ketones
8 issues with whole body metabolism:
constant demand, episodic refueling, changing demand, larger consumption of carbs than available in stores on a daily basis, fats not freely soluble in water, carbons from fats can’t be converted to glucose, oxygen is required to get energy from fats, brains has minuscule stores and can not metabolize fats for fuel
Mechanism of action of glucagon is via:
cAMP
Function force glucagon:
mobilization of fuel: increase glycogenolysis, increase gluconeogenesis, increases lipolysis and ketogenesis
An increase in glycogenolysis leads to:
glycogen synthase inhibition and phosphorylase activation
What hormones inhibit glucagon secretion?
insulin and somatostatin
Fuels that inhibit glucagon secretion:
glucose, ketones, and free fatty acids
hormones that stimulate glucagon secretion:
epinephrine, norepinephrine, gut hormones (VIP, CCK), acetylcholine
Fuels that stimulate glucagon secretion:
amino acids
How many amino acids is the alpha cell made of?
29
How many amino acids is the alpha-chain of insulin made of?
21
How many amino acids is the beta-chain of insulin made of?
30
How many peptide chains make up insulin?
2
Main targets of insulin:
liver, muscle, and fat (in terms of fuel homeostasis)
Mechanism of action of insulin:
via tyrosine kinase receptor
Functions of insulin:
storage of fuels
Functions of adipocytes:
stimulaton of glucose uptake, storage, and glycolysis (alpha-glycerol-P), stimulate free fatty acids biosynthesis, inhibition of hormones sensitive lipase
Functions of muscle:
stimulate glucose and amino acid uptake, storage of glucose, glycolysis and protein synthesis
Functions of liver:
inhibits glycogenolysis, promotes glycolysis over glucogenesis, promotes formation of triglycerides
Fuels that stimulate insulin secretion:
glucose, amino acids, and free fatty acids
Hormones that stimulate insulin secretion:
acetylcholine, GI hormones (GIP), glucagon
Indirect actions of insulin secretion via effects on glucose levels:
growth hormone and cortisol
hormones that inhibit insulin secretion:
somatostatin, epinephrine, norepinephrine (alpha-2 receptors)
What cells release somatostatin?
delta cells
functions of somatostatin:
inhibits insulin, glucagon, growth hormone and TSH secretion (hypothalamic inhibitory hormone)
Role of epinephrine and norepinephrine on adipocytes in fuel homeostasis:
increase hormone sensitive lipase (hydrolysis of fats to glycerol and FFA’s)
Role of epinephrine and norepinephrine on muscle in fuel homeostasis:
increase glycogenolysis and glycolysis (calorigenic)
Roles of epinephrine and norepinephrine on liver in fuel homeostasis:
increase cAMP (same action as glucagon)
Action of growth hormone on adipocyes:
decrease formation of alpha-glycerol-P and increase sensitivity to epinephrine/ norepinephrine (these break down glucose and glycogen)
Action of growth hormone on body:
decrease sensitivity to insulin
Functions of cortisol:
decrease sensitivity to insulin, required to mobilize protein, permissive action on adipocytes
Function of thyroxine:
regulates metabolic rate
Which Type of diabetes in juvenile onset?
Type 1, insulin dependent
True or False? Type 2 diabetes is insuin dependent.
F. non-insulin dependent
True or False? Some tissues can only metabolize glucose.
T
What, besides glucose can muscle metabolize?
free fatty acids and ketones, right?
True or False? Carb are water soluble.
T
glucose in our body at one time
20g (about 500 g needed for one day)
What is the problem with transporting fats?
lipid soluble
What is required for gluconeogenesis?
glycerol + amino acids
True or False? The largest store is what we need the most of.
F. Smallest
True or False? Brain is insulin dependent.
F
True or False? Muscle is insulin dependent
T
huge anabolic hormone:
insulin
Goal of insulin:
drive glucose into periphery
Primary store of large chain carbohydrates.
liver
Glycerol + amino acids =
feed into reverse glycolysis, de novo glucose synthesis
Low carbohydrates diet (high fat, low carbohydrates):
First week of weight loss, rapid loss, water loss due to metabolism of glycogen stores (glycogenolysis)
ketogenesis uses this process:
Beta oxidation
How long to u regulation enzymes in process to use ketone bodies to derive energy?
one week
NO carbs at all, ketones develop, leads to:
ketoacidosis, pH drops (almond breath)
How to control seizure activity in children?
low carbohydrates, high protein diet to put them in ketosis (decreased pH), decreases action potentials
What type of mode is insulin in?
anabolic modes
What type of hormone is glucagon?
ketogenic hormone
True or False? Muscle has a glycogen store.
T. does not contribute much, different time constant
Glycogen break down is done via this enzyme:
glycogen phosphate
Beta cells make up what % of the islet of Langerhans
about 60%
inner core of islet:
beta cells, 25% are alpha that are secreting glucagon, delta cell (somatostatin) about 10%
Functions of somatostatin :
universal inhibitor, (gut, gastric secretion, neurotransmitter, glucagon and insulin secretion inhibition
Why does somatostatin inhibit BOTH insulin and glucagon?
Fast time constant, lengthens the duration of effect
What type of feedback systems is used to control glucose release?
negative feedback
Primary target organ of glucagon:
liver
What process is targeted in the liver in the decreased plasma glucose state:
glycogenolysis
Gluconeogenesis uses what compounds?
glycerol, glucogenic amino acids, pyruvate, and lactate
No insulin:
no anabolic affect, shift toward catabolism
Precurso to insulin
pro-insulin molecule
Where is insulin stored?
granules in beta cells
How is insulin released?
insulin + c peptide in 1:1 ration
When can you use the fact that insulin + c peptide is released in a 1:1 ratio?
Type I or Type II, can not always distinguish between endogenous insulin vs. exogenous. Test for C-peptide. You know which it based on ratio
Unique aspect of insulin receptor structure:
receptors and kinase activity all in one (receptors and signal transduction process in one)
Kinases act on:
insulin receptor substrates
Net effect on target tissue of insulin:
activate, PDGF, EGF, all growth factors are one half of the insulin receptor (1 alpha, or 1 beta, etc.)
What do you do with insulin?
increase glucose up take and transport
How is glucose transport up regulated
at the levels that is already in the membranes
What is the back up store of transporters?
submembrane pool not yet incorporated into membranes, can’t transport glucose
How is the beta cell being controlled?
glucose in blood increases, glucose crosses transporter, glucose need to be metabolized to provide signal so cell secretes insulin, the metabolic process (deg of glucose) provides energy to depolarize cell, oxidize to produce ATP, under resting conditions a channel opens to maintiain the cell in the hyperpolarized state. Lose K out of the cell, increase the membrane difference. ATP present, close K channel, depolarize the cell, Volatge activated Calcium channels up, calcium comes in, starts activating, and eventually allow pool of protein-insulin and insulin to be processed. Proteases activated to convert the insulin
Secretion of insulin is __ dependent.
Calcium dependent process
Why does the Ca channel need to be depolarized?
because the channel has a higher threshold than the AATP channel (?)
What is used in the body in lipogenesis?
Free fatty acids and glycerol
True or False? Insulin inhibits glycogen synthase.
F. stimulates
True or False? Glucagon has strong effects on muscle.
F.
HSL:
hormone sensitive lipase, breaks down triglycerides, when were are trying to build fat stores we inhibit this with insulin
Affect of glucagon on HSL:
stimulates
4 hormones that try and counter the actions of insulin:
glucagon, cortisol, epinephrine, norepinephrine, human growth hormone (all try to elevate glucose) (counter -regulatory hormones to insulin)
First line of defense against low glucose levels in the blood:
glucagon
How many hormones do we have that prevent glucose levels from getting too low?
4
Cortisol is categorized as a:
glucocortocoid (adrenal cortico hormone)
epinephrine is released from here to increase glucose levels:
adrenal medulla
What cells release glucagon
alpha cells, islet cells of the pancreas, total circulatory to the liver first
What happens after glucose leaves the liver?
lipolytic effects of glucagon at the adipose tissue
