random last minute questions

[lilmisty]

Long time lurker, first time poster!

Would someone mind lending me a hand with these two completely unrelated questions?

1. Glucocorticoids. I get what they do, but how come one of my books says they increase glycogen synthase activity? Doesn't this oppose their ability to raise the blood sugar and whatnot? ALSO, how do these "make you fat"? If you're breaking down all that fat (increased lipolysis), wouldn't they make you skinnier?

2. So I've looked over old threads and they kind of confuse me--can someone explain how fibrate drugs can give you gallstones? The mechanisms don't seem to add up...I don't see why fibrates give you gallstones but the other lipid lowering drugs don't?

Thanks everyone! I hope to contribute as well

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[surgok]

I can answer one question for you. They make you fat because increased glucose -> increased insulin -> increased fat deposition due to insulin.

 

[thehundredthone]

1. Glucocorticoids do induce glycogen synthase. Hyperglycaemia is due to decreased peripheral uptake of glucose and a permissive effect on glucagon, rather than stimulating glycogenolysis directly. Glucocorticoids influence the maturation of preadipocytes into adipocytes thus causing central and cervical fat deposition.

http://www.ncbi.nlm.nih.gov/pubmed/114752

2. Fibrates reduce the conversion of cholesterol to bile acids by inhibiting 7 alpha hydroxylase, hence increasing the cholesterol content of bile, while also reducing it's solubility, They also decrease bile acid excretion causing supersaturation of bile thereby leading to cholesterol stones..

 

[Ionian]

I think is sufficient to know bile is made up of 3 components, cholesterol, triglycerides and bile acids.
Triglycerides and bile acids solubilize cholesterol, any disturbance to the balance in these 3 components leads to stones.
(Increased Cholesterol, or decreased triglycerides/bile acids)

It's sufficient to know know Fibrates decreased triglycerides profoundly via LPL activation, I wouldn't say its as important to know the cholesterol is increased in the bile through memorizing some other mechanism, because more importantly its the relative percent increase in cholesterol due to the decrease in the triglycerides, so I sort of disagree with the mechanism posted above.

This way, you know the original mechanism of fibtrates (Increase LPL, decrease triglycerides) and still can come to the conclusion 'cholesterol is increased in the bile', mainly because one of the other components is decreased....

In the same way cholestyramine decreased bile acids ---> Increased relative cholesterol --> Stones

 

[DeeJay2728]

7 alpha hydroxylase is key to understanding how all of the above works. If you inhibit the conversion of cholesterol to bile acids, you're liver tries to compensate and make more bile acids. We normally recycle our bile acids (enterohepatic circulaton), so this balance is kept by "re routing"our cholesterol sources, into making more bile acids. In order to do this, the liver has to take up more cholesterol sources (up regulate more receptors) to balance for the loss of bile acids.