Endogenous v. Exongenous Hormones

I'm going to be using insulin as my example in this post.  Endogenous insulin is the insulin produced in your body by your pancreas.  Exogenous insulin would be that derived from outside the body - e.g. insulin injections.  For the most part exogenous hormones are obtained through some "pharmaceutical" route.  In the case of insulin, subcutaneous injections.

Now I’m sure most of my readers are familiar with the picture below:

It is accompanied by the following paragraph in GCBC:

Having seen this, it is now obvious to us that insulin injected into fat cells of the thighs can cause fat to preferentially accumulate in those fat cells.  Taubes would have you look at this photo, however, and equate what happened to this poor woman, who obviously didn't rotate injection sites, to what is happening in your whole body when you eat carbohydrates and your pancreas secretes insulin.

Endogenous insulin production and stimulation is a very intricate thing.  This is why insulin therapy for Type 1 diabetics is so difficult.  

Endogenous Insulin:  

All insulin produced by the pancreatic ß-cells is released into the portal vein where it is extracted by the liver and redistributed into general circulation.   

There are different types of insulin secretion:

Basal:  This is mostly controlled by free fatty acid levels and endogenous hyperglycemia (uncontrolled gluconeogenesis)  that induce a lower level pulsatile/periodic secretion. 

Glusose Stimulated Insulin Secretion (GSIS):  This is the "acute" insulin response to exogenous glucose.  It is described as biphasic:  a short "burst" of insulin that is fairly short-lived followed by a longer acting lower sustained release.

Other:  Incretins (e.g. GLP-1, GIP), amino acids, etc. are known to stimulate insulin secretion.  This secretion is either be part of GSIS mechanism or similar to it in nature.

Endogenous insulin has a half-life in plasma of 5-10 minutes (I've seen various values).  This can be influenced by the action of insulin-degrading enzyme (IDE) which breaks down insulin.

Now ....


Exogenous Insulin

Up until recently, with the advent of the insulin pumps, insulin was administered via injections into fat pads beneath the skin - subcutaneous injection.  Potential sites are shown below:

This is because insulin will not survive the digestive system, ruling out oral administration.  The absorption of a insulin (or any drug for example) by this route is dramatically different from, say, placing a tube in the portal vein and delivering insulin by that route.    

This differs from both biphasic and pulsatile basal delivery in that a single injection is a "bolus" dose.  One time, usually supraphysiological (more than would normally be secreted endogenously) levels of insulin do not mimic endogenous production by a long shot.  This, in and of itself renders observations of exogenous insulin therapy rather absurd to elucidate the implications of endogenous insulin production - even excessive insulin production.  

But there's more.  I could cite from many sources, but basically not all insulin is even remotely alike.  This is a screenshot of the table from WebMD:  {click to enlarge}

Exogenous insulin has varying half-lifes.  Without researching all the pharmacokinetic mechanisms here (means by which levels go up and down and how long it takes), the various (evil?) drug companies have come up with ways to sidestep IDE, etc. and allow the exogenous insulin to either absorb more slowly or degrade less rapidly to act over a longer or shorter period.  

So, do the various trials that show some weight gain with aggressive insulin therapy have meaning for why you or I get fat?  I'd say not.  Exogenous insulin is so clearly different from endogenous.