Endocrine 1

(Difference between revisions)

Current revision as of 11:32, 9 March 2012

4i7usU I think this is a real great blog.Thanks Again. Really Great.

Insulin receptor:
- Tetrameric: alpha, alpha, beta, beta
- Binds, activates kinase activity
- Autophoses to increase kinase activity
- Phoses stuff to activate and deactivate.
- Deactivates gene expression and growth
- Activates glycogen synthesis, protein synthesis, anti-apop, and anti-lypolysis
We're looking all the way down stream to find out what's broken in insulin-resistant states.

Type 1: failure to make insulin b/c beta cells are killed by auto immune response
- 5-10%
Type 2: Insulin improperly used; resistance combined with deficiency in production
Gestational diabetes:
Prediabetes: lots of people.

Beta cell mass has decreased.
Some event causes an immune response.
Average diagnosis age = 7-8
- Because they have to lose their beta cell mass before symptoms show up.
At first the glucose can be normal.
Then c protein ...
So we given them insulin
- Shots, pumps, etc.
- Pumps are the best regulators.
We'd like to use transplantation
- Mixed success

A given amount of glucose intake requires a larger amount of insulin release to maintain blood glucose regulation.
Mutations of the insulin receptor are rare; think leprochonism.
Metabolic syndrome:
- Hyperlipidemia
- Cardiovascular disease
- Glucose abnormalities
- 3 of 4 diabetes die of a vascular complication
Even normal people have periods of insulin resistance; normally the pancreas compensates.
- For example, cortisol can cause these periods.
In type 2, eventually the beta cells go from highly overcompensating and then die.

Fasting plasma glucose test
- Have them fast
- Then have them come in and measure their plasma glucose.
- Normal < 99 mg/dl
- Pre = 100-125
- T2DM > 126 mg / dl
YOu can also do a glucose tolerance test
- Drink lots of glucose
- NOrm < 139
- Pre = 140-199
- T2DM > 200

Turns out it isn't the insulin receptor.
In all the studies, we do see that an inflammatory response and lipid overload can wreak havoc on glucose regulation.
- They increase some bad serine kinases that phos the receptor to arrest the kinase ability and thus the decrease.
Even high insulin can cause resistance to insulin.
Hyperglycemia increases resistance at muscle and fat.
Dyslipidemia occurs:
- Decreased HDL
- Increased TAGS
- Increased Small, dense LDLs
We also see increased blood pressure and coronary artery disease.
Circulatory system damage, renal failure, neuropathy, retinopathy.

B/c insulin resistance can be caused by many things, we have to treat in many different ways: change the lipids, change the receptor, change signaling pathways, etc.
Sulfonylurea
- Subclasses: meglitinides, nateglinides
- Enhance insulin secretion
- 1950s
- Work on beta cells on a potassium channel to cause polarization to increase Ca influx to increase vescicular release.
Guanines
- Work on liver
- Favorite of physicians
- Metformin
- Works best...for a while
- Increases liver sensitivity to insulin
- Prevents glycogen breakdown by inhibiting glucagon response
Alpha glucosidases
- Inhibit ?
Thiazolidinediones
- Increase sensitivity of muslc eand adipose to insulin
GLP1 is an encrenton
- Has a very short halflife
- Degraded by DPP4
- Lizard spit has a glp-like protein that isn't degraded by dpp4
- Mimetics (byetta) is now given to pts.
Jenuvia
- Dpp4 inhibitor

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-===Insulin Secretion and action===
+i7usU I think this is a real great blog.Thanks Again. Really Great.
-*Three gut homrones: CCK, GIP (glucose insulintropic protein, and GLP1).
-**Released from gut
-**Act on pancreas to increase insulin release.
-*Other things that affect insulin:
-**Glucagon
-**Beta-adrenergic agonists
-**Somatostatin
 ===Insulin actions===