the major hormones that regulate metabolism are (blank) and (blank)

they respond minute-to-minute in response to changes in (blank1)

they indirectly provide efficient (blank1) to RBCs and brain by directly altering the metabolic activities of (blank), (blank), and (blank)

insulin and glucagon

blood glucose

liver, adipose, and muscle

insulin from pancreatic beta cells

glucagon from pancreatic alpha cells

insulin is synthesized as a (blank).

the pre [or (blank)] is cleaved in the (blank).

The Connecting [or (blank1)] is removed by proteases that cleave at pairs of (blank) amino acids as the pro-insulin is processed.

The mature insulin is STORED in secretory vesicles with the (blank1) and with the cleaved (blank)s 

All are released in response to (blank)

prepro-peptide

signal sequence (pre) cleaved in the ER

C-peptide removed by proteases that cleave at pairs of BASIC amino acids

C-peptide and cleaved amino acids

increased blood glucose

secretion of insulin in response to glucose involves following pathway:

1. glucose is transported into the (blank) cell by (blank) and then is phosphorylated by (blank).  Both of these proteins can respond to changes in blood glucose that occur during a meal because their Km's (Kd for the receptor - strength of ES interaction) are in the range of blood glucose concentration that occurs after a meal.
2. Glucose metabolism increases (blank1) levels
3. (blank1) closes a (blank) channel
4. This results in the opening of a (blank)
5. (blank) enters the cell and activates (blank)s which phosphorylate proteins leading to release of (blank)

beta cell

Glut2

glucokinase

ATP

potassium channel

voltage-sensitive calcium channel

calcium

protein kinases

insulin

Insulin signaling and the metabolic effects of insulin

insulin travels through the bloodstream to many target tissues.  Chief among these are (blank), (blank), and (blank).

liver

adipose

skeletal muscle

tyrosine phosphorylation 

called AUTOPHOSPHORYLATION

1. insulin receptor substrates (IRS)
2. Shc

PI3-kinase 

or phosphatidylinositol 3-kinase

p110 catalytic

p85 regulatory.

Insulin signaling and the metabolic effects of insulin (PI3-kinase has 2 subunits)

phosphotyrosine 

IRS (insulin receptor substrates)

p110 Catalytic subunit of PI3-kinase

Inositol lipids

regulation

Akt

Glut4 glucose transporters

Insulin signaling and the metabolic effects of insulin

insulin signaling often activates a (blank), called (blank), which de-phosphorylates metabolic enzymes, resulting in their activation or inhibition.  

(blank1) blocks glycogen synthesis and thus, is inhibited by insulin action.  [(blank1)'s inhibition will stimulate glycogen synthesis.]

activation of (blank) promotes protein synthesis

phosphatase called PP-1

GSK-3

p70

Metabolic effects of Insulin - LIVER

Increased: ?  (1 catabolic and 5 anabolic mechanisms)

Decreased: ? (all catabolic)

Increased 

• glycolysis
• fatty acid synthesis
• glycogen synthesis
• triacylglycerol synthesis
• VLDL release
• protein synthesis

• gluconeogenesis
• glycogenolysis
• fatty acid oxidation

Metabolic effects of Insulin - ADIPOSE

Increased: ?? 1 catabolic, 2 anabolic and increase uptake of (blank)

Decreased: ?? just one catabolic (think of what happens during fasting state)

Increased

• glycolysis (catabolic)
• fatty acid synthesis (anabolic)
• Triacylglycerol (TAG) synthesis (anabolic)
• increased uptake of TAGs from chylomicrons and VLDL

• TAG hydrolysis (catabolic)

Increased: 

• glycolysis
• glycogen
• protein synthesis

• glycogenolysis

Glucagon signaling and Metabolic effects of glucagon

Glucagon is released from (blank) and travels to two target organs: the (blank) and (blank), where it binds to a cell surface receptor.  There are no glucagon receptors in (blank)

pancreatic alpha cells

liver and adipose

muscle

G-protein

alpha, beta, and gamma

guanine nucleotides

G-alpha-s

GDP

GTP

[image]

Adenylate Cyclase

cAMP (cyclic AMP)

PKA (protein kinase A)

CREB - cAMP response element binding protein

[image]

Metabolic effects of Glucagon - LIVER

Increased: ?? (think opposite of insulin)

Decreased: ??

Increased:

Gluconeogenesis

glycogenolysis

fatty acid oxidation

Decreased:

glycolysis

fatty acid synthesis

glycogen synthesis

Metabolic effects of Glucagon - ADIPOSE

Increased: ?? 

Decreased: ??

Increased: 

TAG hydrolysis (NEED ENERGY!)

Decreased: 

N/A

Metabolic Effects of Glucagon - Muscle

Increased: ?? 

Decreased: ??

NO EFFECTS (trick question)

THERE ARE NO GLUCAGON RECEPTORS ON MUSCLE MEMBRANES

Other counter-insulin-regulatory Hormones

What are two hormones that, like glucagon, also increase when blood glucose decreases?

epinephrine & cortisol

[image]

Metabolic effects of Epinephrine - LIVER

same as (blank)

same as glucagon in liver

Metabolic Effects of Epinephrine - ADIPOSE

same as (blank)

same as glucagon

Metabolic Effects of Epinephrine - MUSCLE

Increases: ??

Decreases: ???

Increases:

Glycogenolysis and

Glycolysis

Decreases:  

Glycogen synthesis

Metabolic Effects of Epinephrine - MUSCLE

Why would Epinephrine increase both glycogenolysis and glycolysis?

role of glycogenolysis is to...

glycolysis give energy to ... by ...

**but why would Epi decrease glycolysis in liver?

glycogenolysis = breaks down glycogen --> glucose

muscle feeds off glucose

uses glycolysis

decreases glycolysis in liver since all the glucose from the liver is given primarily to brain and RBCs who need it most!

Metabolic effects of Epinephrine

Epi binds to a receptor that is also coupled to (blank)

thus, epinephrine also increases (blank) levels, therefore there is an overlap between epinephrine and glucagon action, but 2 important differences exist...

1. ?
2. ?

G-alpha-s

cAMP

1. glucagon does not bind to the Epi receptor and Epi does not bind to the glucagon receptor
2. there are Epi receptors in muscle and there are similarities and differences in cAMP action in muscle compared to liver

Metabolic effects of cortisol

Cortisol is a (blank).  It is hydrophobic and a lipid and thus able to pass through (blank).

Once inside cells, cortisol (cort) binds to a receptor that is a (blank).

the cort/receptor complex will regulate (big blank)

steroid

plasma membrane

transcription factor

will regulate the transcription of genes encoding metabolic enzymes

Metabolic effects of cortisol - LIVER

Increased: ??

Decreased: ??

Metabolic effects of cortisol - ADIPOSE

Increases: 

Decreases:

Metabolic effects of cortisol - MUSCLE

Increases: ??

Decreases: ??

Increases: Proteolysis

Decreases: glucose uptake

Metabolic effects of cortisol - Main effect of cortisol??

The main effect of cort is to (blank) blood glucose by increasing gluconeogenesis.  

The gluconeogenic precursors are mostly (blank)s and (blank).

cort deficiency is called (blank) disease

in chronic stress, effects of cort cause loss of muscle mass/strength, and re-distribution of fat from sub-cutaneous regions to the abdomen, which increases risk of (blank) disease.

the reasons for the unfavorable deposition of fat are not clear, but could result in part from the possibility that the (blank) effect of cort is really "designed" to generate (blank) for gluconeogenesis.  The FFA are not necessarily oxidized, but may be re-deposited in visceral fat.

increase

amino acids and glycerol

Addison's disease

cardiovascular disease

TAG hydrolyzing effect of cort

generates glycerol for gluconeogenesis