Endo - Pharm - 1-5 Insulin

Front 1

Speed of action
Insulin Lispro

Back 1

Very rapid-acting
(15 min)

Very quick because there is a switch in the beta chain so aggregation and hexamers don't form. So the insulin is already in a nice monomer form.

Front 2

Speed of action
Regular insulin

Back 2

Rapid-acting
1 hr

Not super fast because it is injected as a precipitate so it takes time for it to be dissolved an act.

Front 3

Speed of action
NPH (neutral protamine hagedorn) insulin suspension (isophane)

Back 3

Intermediate-acting
within 2 hours.

Front 4

Speed of action
Insulin glargine

Back 4

Long-acting (peakless)
within 4 hours.

Has 2 arg and 1 glycine residues. Only goes into solution at an acidic pH. Is a precipitate at other pHs. So it remains mostly as precip in blood and dissolves very slowly over time.

Front 5

Synthesis of insulin

Back 5

Preproinsulin is made which has the signal sequence on it to direct it to the ER. Signal sequence is then removed and the molecule is called proinsulin.

Proinsulin is arranged in the order B-C-A. C (in the middle) is cleaved and B and A are joined by disulfide bonds.

Insulin is the molecule of A and B chain joined by disulfide bonds. C-peptide is not part of mature insulin.

Front 6

Secretion of insulin

Back 6

It is produced by pancreatic beta cells, stored in granules, and is released in response to nutrients (rapid release)

There is also a de novo synthesis/release mechanism.

Front 7

When insulin is released, what else goes along with it?

Back 7

C-peptide
Pro-insulin
Amylin - this slows gastric emptying and therefore more nutrients have a chance to be absorbed.

Front 8

Glp-1

Back 8

This is released from the gut in response to nutrients and it further stimulates insulin release.

Front 9

Where is insulin secreted?

Back 9

To the portal system to the liver. Liver degrades half of the insulin, and the other half gets out of the liver to muscle and fat.

Front 10

Molecular mechanism of insulin secretion

Back 10

IN BETA CELLS OF THE PANCREAS

With increased glucose flow through the glucose transporter, ATP levels increase and close the K+ channel thus depolarizing the cell (less flux outside).

The Ca++ channel opens in response to this depolarization and results of the exocytosis of the granules containing mature insulin (and C-peptide as well...).

Front 11

With an oral infusion of glucose, will there be more or less insulin released compared to IV?

Back 11

More insulin release because of Glp-1 effect from gut

Front 12

What does insulin do on a very basic level?

Back 12

Promotes the uptake of glucose from the blood

Promotes anabolism

Inhibits catabolism.

Front 13

What does insulin do to FAs, glucose, AAs...

Back 13

Stimulates...
conversion of glucose to glycogen (liver)

Glucose to TGs (adipose

Glucose to protein (muscle)

AAs to protein (muscle)

FAs to TGs (adipose)

Glucose to fatty acids.


IT ALSO INHIBITS AAS TO GLUCOSE, AND ANY CATABOLISM (e.g. TGs to FAs, glycogen to glucose, or protein to AAs).

slide 8

Front 14

Insulin receptor

Back 14

Tyrosine kinase

2 alpha (ligand binding) and 2 beta (signaling) subunits

Leads to phosphorylation of pathways via the activation of many kinases.

Front 15

Rapid effects of insulin

Back 15

Glucose receptor (already preformed) is put onto membrane.

Front 16

Long term effects of insulin

Back 16

Activates genes for long-term action

Front 17

Intermed effects of insulin

Back 17

Modifies enzymes

inactivates TG lipase phosphorylases

activates pyruvate dehydrogenase and glycogen synthase

Front 18

General relationship btwn time of onset and duration

Back 18

Longer time of onset, longer duration.