Hormonal Regulation And Signal Transduction

Front 1

How is insulin secreted?

Back 1

Secreted by Beta cells of pancreas

It is secreted as an A and B chain, with disulfide bonds

Front 2

How can you measure how much endogenous insulin someone is making?

Back 2

Measure C peptide levels

Front 3

What are the 4 key effects of insulin?

Back 3

1.) Stimulates glycogen synthesis in muscles in liver by promoting the dephosphorylation of glycogen synthase (remember glycogen synthase is active in its unphosphorylated state)

2.) Stimulates uptake of glucose by muscle cells and adipocytes. Promotes fusion of GLUT4 glucose transporter with plasma membrane.

3.) Promotes of uptake of branched amino acids (favoring build-up of protein)

4.) Stimulates protein synthesis and inhibits protein degradation

Front 4

What effects does insulin have in adipocytes?

Back 4

Insulin inhibits lipoprotein lipase,

activates the pyruvate dehydrogenase complex and acetyl-CoA carboxylase

Front 5

What is glucagon?

Back 5

Small peptide hormone (29 AA's)

Secreted from alpha cells of pancreas

Front 6

What is the primary target of glucagon?

Back 6

Its primary target is the LIVER!!!

NO effect on muscle

Front 7

What are the effects of glucagon?

Back 7

1.) Stimulates glycogen breakdown by inhibiting glycogen synthesis and phosphorylating glycogen synthase. It also phosphorylates glycogen phosphorylase.

2.) Inhibits fatty acid synthesis by diminishing production of pyruvate and lowering activity of acetyl-CoA carboxylase

3.) Stimulates glucose synthesis by lowering Fructose-2,6-bisphosphate

4.) Activates liapse in adipocytes

Front 8

What does glucagon phosphorylate?

Back 8

Glycogen phosphorylase (activating it) and glycogen synthase (de-activating it)

Front 9

How does glucagon affect fatty acid metabolism?

Back 9

Glucagon inhibits fatty acid synthesis by inhibiting production of pyruvate and lowering the activity of acetyl-CoA carboxylase

Front 10

What effects does GLUCAGON have on acetyl-CoA carboxylase?

Back 10

Glucagon diminishes the activity of acetyl-CoA carboxylase! Want to inhibit fatty acid synthesis!

Front 11

How does glucagon stimulate glucose synthesis?

Back 11

Glucagon diminished F-2,6-BP levels in the liver!

Front 12

Difference between catecholamines and glucagon?

Back 12

Glucagon is released in response to low blood levels of glucose. Glucagon only affects liver.

Catecholamines are released in response to stress. Catecholamines have a strong effect on muscle and adipose tissue (as well as liver)!

Front 13

What do the catecholamines do?

Back 13

1.) Mobilize glycogen in muscle and liver and TAGs in the adipocytes

2.) Stimulate secretion of glucagon and inhibit secretion of insulin

3.) Inhibits uptake of glucose by muscle, switch over to fatty acids

4.) Increase the amount of glucose released into the blood by the liver

Front 14

How is insulin released from the pancreatic Beta cell?

Back 14

Beta cell expresses constitutive glucose transporter (GLUT2), which senses levels of glucose in blood.

Glucose is converted to ATP in pancreatic beta cell, ATP binds K+ channels and promotes depolarization of plasma membrane. This opens voltage gated Ca2+ channels, Ca2+ causes exocytosis of insulin from the cytoplasm.

Front 15

How does the insulin receptor

Back 15

Insulin binds to alpha subunits of receptor, causes conformational changes in intracellular Beta subunits, causes autophosphorylation of Beta subunits. Tyrosine gets phosphorylated. Starts intracellular signal transduction cascade.

Front 16

What is one intracellular cascade activated by insulin in muscle cells?

Back 16

Insulin activates protein kinase B

Front 17

What are the two effects of protein kinase B?

Back 17

1.) Phosphorylates GSK-III, inactivating it, and preventing it from phosphorylating and inactivating glycogen synthase

2.) Protein Kinase B increases the number of GLUT4 transporters in the plasma membrane

Front 18

How does insulin cause the increase in GLUT4 transporters on plasma membrane?

Back 18

Insulin activates Protein Kinase B, which promotes the fusion of GLUT4 with plasma membrane

Front 19

What affect does insulin have on GSK-III?

Back 19

Insulin activates protein kinase B ---> inactivates GSK-III by phosphorylating GSK-III ---> glycogen synthase is not phosphorylated and thus it is activated

Front 20

What is another mechanism for increasing GLUT4 transporters on plasma membrane?

Back 20

EXERCISE!

Front 21

What happens when glucagon and catecholamines bind beta adrenergic receptor on plasma membrane?

Back 21

Both activate adenylate cyclase, converting ATP to cAMP

Front 22

What activates adenylate cyclase?

Back 22

Glucagon and catecholamines binding receptors on plasma membrane.

Front 23

What does adenylate cyclase do?

Back 23

It promotes conversion of ATP to cAMP!

Front 24

What happens when catecholamines bind ALPHA-adrenergic receptor?

Back 24

Activates G protein, GTP binds phospholipase C, which cleaves PIP2 in plasma membrane into diacylglycerol and IP3.
IP3 binds calcium channels in ER membrane and releases sequestered Ca2+
Diacylglycerol activates protein kinase C

Front 25

What does phosholipase C do?

Back 25

Cleaves PIP2 into IP3 and Diacylglycerol

Front 26

What affect does IP3 have?

Back 26

Releases Ca2+ from ER, and this Ca2+ activates protein kinase C.

Front 27

What happens when cAMP is produced?

Back 27

It binds to a regulatory subunit that activates Protein Kinase a

Front 28

How is protein kinase C activates?

Back 28

Catecholamines binding to alpha-adrenergic receptors.
Phospholipase C cleaves PIP2 into IP3 and DAG.

IP3 opens Ca2+ channels on ER membrane.

DAG and Ca2+ activates protein kinase C

Front 29

How is protein kinase A activated?

Back 29

By cyclic AMP, from binding of catecholamines and glucagon to beta adrenergic receptors!

Front 30

What does protein kinase A do?

Back 30

1.) Phoshorylates glycogen synthase (inactivating it) and glycogen phosphorylase (activating it)

2.) Inhibits through phosphorylation acetyl-CoA carboxylase (committed first step in fatty acid synthesis)