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Re: [IP] Continuing Humalog / Velosulin saga

Thanks Mary Jean (and Bob), but I still don't fully understand what is
going on.  There also may be some confusion about what insulin is supposed
to be doing.   My understanding of how insulin works is that the insulin
molecule binds to insulin receptors on cells in muscle, liver, etc (but not
in nerves or brain), which then allows glucose to enter the cell.   All
insulin (R, NPH, L, UL, H,...) works that way.  Insulin does not need to be
broken down to work (in fact if it is, it won't bind to the insulin
receptors and won't work) .  It also isn't absorbed into and doesn't enter
cells--it just binds to the receptors on the cell surface.  Once it reaches
the cells H works exactly the same way as R or any other kind of insulin.
The longer acting insulins are slower only because they are absorbed from
the injection site into the blood more slowly. This occurs because they are
bound with other chemicals that makes the combination bigger and slows down
the diffusion from the subcutaneous tissue into the nearby capillaries.
	My question I guess was perhaps a bit more scientific, i.e., what
is it about H that makes it diffuse more rapidly that R?  Diffusion is
normally slower for bigger molecules, but H and R are almost indentical in
molecular weight.    Is it possible maybe that the reversal of lys and pro
in H causes the insulin protein to fold up into a smaller shape, that lets
it move more easily?

<<<<<<<<<From: email @ redacted
Subject: Re: [IP] Continuing Humalog / Velosulin saga

I'll take a stab at it.  In the Humalog molecule, the amino acids in positions
28 and 29 in the b-chain are reversed (these are lys<b28> and pro<b29>, hence
its name). This causes a "weak link" in the chain, enabling the molecule to be
broken down into its components much quicker than the more robust Regular
insulin molecule.  It is when the molecule breaks down, that the blood glucose
lowering effect is started.

I'm sure there is "a bit more to it" than that, but this is the general idea.
Mary Jean>>>>>>>>>>>

<<<<<From: Bob Burnett <email @ redacted>
Subject: Re: [IP] Continuing Humalog / Velosulin saga

My apologies in advance for what may be a boring, lengthy ramble. Please
delete if not interested ;-)

Some other musings on Humalog / Regular / Velosulin:

Humalog is absorbed by the cells much more quickly than other synthetic
insulins (obvious, but important). It is possible that this faster cellular
absorption may also eventually affect the cells, "tiring them out" in
effect. It's entirely possible that this end result is independent of any
other factors being discussed (antibodies, etc).>>>>>

Wayne Mitzner
Department of Environmental Health Sciences
The Johns Hopkins School of Hygiene and Public Health
615 N. Wolfe St.
Baltimore, MD 21205
Tel. 410 614 5446
Fax 410 955 0299

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