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Hormonal Regulation of Fuel Metabolism Tissue Differences, Review of Glycolysis

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What are the three ways glucose levels can be regulated?
a) Blood levels of nutrients (read by cells)⬦ b) Hormones⬦ c) Neuronal
What is the normal homeostatic concentration of glucose in the blood?
80-100 mg/dL (~5 mM)
Which four tissues rely heavily on the glycolysis?
a) lens⬦ b) RBC⬦ c) Kidney Medulla⬦ d) Brain
What type of hormone is anabolic and made on ß-cells in the pancreas?
Insulin
Which type of hormone is catabolic and made on ∂-cells in the pancreas?
glucagon
1. Which type(s) hormones are short term?

2. which hormone (that is antagonistic to insulin) is released by neurons in the adrenal medulla?
1. epinephrine and norepinephrine

2. norepinephrine
Where are epinephrine and norepinephrine produced?
norepinephrine is made in the medulla of the adrenal gland and epinephrine is made in the cortex.
Which hormone is long term?
Cortisol
Which hormones are counter regulatory to insulin?
glucagon, epinephrine, norepinephrine, corisol
With respect to fuel metabolism, what are the regulatory steps in glucagon production?
low blood sugar sensed by ∂-cells in pancreas > glycogen production
Which hormone maintains blood glucose levels during fasting?
glucagon
Which hormone stimulates fatty acid synthesis and storage after a high-carbohydrate meal?
insulin
Which hormone activates gluconeogenesis and glycogenolysis (liver) during fasting?
glucagon (cortisol causes gluconeogenosis)
1. Which hormone stimulates amino acid uptake and protein synthesis in muscles and fat cells?

2. Which hormone stimulates the conversion of amino acids to glucose in the liver?

3. Which hormone stimulates glucose uptake and convers
1. insulin

2. Glucagon

3. Insulin
Which hormone can cause the production of glucose from nonglucose precursors?
glucagon
Which hormones stimulates fatty acid release from adipose tissue?

what effect would Epi have on the glycogen:pyruvate (lactate) ratio?
glucagon (activates), epinephrine, cortisol

increase in conversion of glycogen to pyruvate.
Which hormone stimulates amino acid mobilization from muscle protein?
cortisol
How do muscles respond to glucagon?
They don't since they have no receptors
What effect does glucagon have on amino acids in the liver?
conversion to glucose (gluconeogenesis)
What effect does glucagon have on fatty acid production in adipose tissue?
Inhibits
What effect does glucagon have on glucose and glycogen in the liver?
Inhibits glycogen production, and mobilizes glycogen to glucose.
What effect does glucagon have on TAGs?
stimulates mobilization to fatty acids
What effect does epinephrine have on insulin and glucagon?
In the pancrease, it inhibits insulin production and stimulates glucagon production.
What effect does epinephrine have on fatty acids and glycerols in fatty acids?
Stimulate mobilization of fatty acids and glycerol
What is glycerol used for?
substrate for gluconeogenosis
What are pyruvate and lactic acid used for (the release of these are stimulated from muscle by epinephrine)?
Precursors for gluconeogenosis
What is the major stimulating regulator of insulin?
Glucose
What are the 3 minor stimulating factors of insulin?
amino acids, neural input, gut hormones
What is the major (+) stimulating regulator of glucagon?
Amino acids
What are the minor stimulating regulators of glucagon?
cortisol, neural (stress), epinephrine, gut hormones
What is the minor inhibitory regulator of insulin?
Epinephrine
What are the 2 major inhibitory regulators of glucagon?
Glucose and insulin
How do gut hormones and amino acids effect insulin and glucagon?
They both stimulate release, but amino acids is a major stimulator of glucagon
Which pancreatic cell make insulin and which make glucagon?
B cells make insulin⬦ A cells make glucagon
What is proinsulin?
It is not an active form⬦ it has the C-peptide still attached
Since the cleavage of the C-peptide is in the middle of the proinsulin, what happens to the two halves?
They are joined by 3 disulfide bonds
What are the two reasons it is better to use C-peptide to measure insulin levels?
1) it clears much slower than insulin. 2) it is a 1 to 1 ratio.
How does insulin increase the amount of glucose uptake in cells?

What does insulin affect, Vmax or Km? why?
Causes the migration of presynthesized Glut-4 to the membrane.

Vmax, since more GLUT-4 receptors are made available to uptake glucose
Does insulin change the Vmax or Km of the Glut-4 receptor and why?
Vmax⬦ changes the capacity⬦ not the function (function would be Km⬦ affinity, etc.)
What are the steps of the signal transduction of glucagon?
1) glucagon binds receptor 2) bound receptor stimulate the G-protein to become activate by GTP 3) active G-protein 4) adenylate cyclase is acived 5) ATP is converted to cAMP (time sensitive because cAMP can be degraded to AMP by a phosphodiesterase) 6) cAMP activates the catalytic subunit of PKA 7) protein is activated leading to a cellular response to release glucose.
Does the phosphatase seen in the breakdown of glycogen or the attenuation of the signal have an associated energy cost?
Yes, in breaking down glycogen and attenuating the signal.
How do tissue respond to only some hormones?
receptor specified
Hormones are released in small amounts. How does this effect its function in cells?
cellular amplification
What are 5 features of the hormonal signaling mechansim?
a) specificity b) amplification c) integration d) modification by other hormones (augment or antagonize) e) rapid termination
What is meant by the integration of the hormonal signaling mechanism?
adenlylate cyclase produces cAMP after initial signal and continues until terminated.
What is meant by augmentation or antagonizing of the hormonal signalling system?
Other hormones can modify a given hormone and thus the overall metabolic effect is cummulative.
What cellular molecules act to antagonize (regulate) the effects of cAMP?
phosphodiesterase and protein phosphatase
What does protein phosphatase do within the G-protein hormone system?
it dephosphorylate the protein (which is activated by PKA) that triggers the cellular response
What does phosphodiesterase do within the G-protein hormone system?
It converts cAMP to AMP
How is it that glucagon goes up in the presence of amino acids?
Insulin is stimulated in the presence of amino acids, but glucagon will go up when insulin is present without glucose⬦ in other words glucagon is striking a balance with the insulin.
What transporter conveys glucose into pancreatic B-cells in response to a high carb meal?

What happens in muscle cells in response to the insulin release?
Glut-2 transporter

Glut-4 receptor translocation to the membrane of muscle cells
What does insulin do to cells that directly inceases the intake of glucose?
It causes the translocation of more Glut-4 receptors
What is the normal fasting serum glucose level?
80-100 mg/dL
What are symptoms of low serum glucose levels (hypoglycemia)?
Due to the brains need for glucose you would see fatigue, confusion, and blurred vision⬦ and in severe cases, headache, loss of consciousness and seizures.
What response would cause anxiety, pallor change, and sweating?
Epinephrine
What 3 things contribute to hypoglycemia?
carb intake, fuel utilization (exercise), and metabolism (glucose uptake, entrance of glucose ATP, and release of glucose from stores)
How is metabolism regulated?
Allosteric and hormonal (glcagon and insulin)
With respect to glucose, what is autonomous secretion of insulin mean?
It is independent of glucose
Is glucagon and epinephrine secretion affected by the hypersecretion of insulin?
No
What is an insulinoma?
it is a mass of insul rich B cells.
What is glycogenolysis?
The degradation of glycogen (see the G-protein pathway)
What are the changes in changes in the blood glucose, insulin and glucagon after a high carb meal?
glucose: initially rises, then falls in response to...

Insulin rises... then eventually falls as glucose levels fall

Glucagon falls in response to glucose increase
What are the changes in changes in the blood glucose, nitrogen, insulin and glucagon after a high protein meal?
nitrogen: increase

glucose is unaffected

Insulin increase then decreases in repsonse to glucagon inhibition of insulin

Glucagon increases due to low glucose levels

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