I was looking up c-peptide, and was surprised to find that it purportedly
exerts beneficial therapeutic effects on diabetes complications

Wikpedia has the following at http://en.wikipedia.org/wiki/C-peptide

Function
C-peptide functions in repair of the muscular layer of the arteries.

C-peptide also exerts beneficial therapeutic effects on many complications
associated with diabetes mellitus [1] , [2], such as for instance diabetic
neuropathy[3] and other diabetes-induced ailments. In the kidneys, C-peptide
prevents diabetic nephropathy [4], [5], and in the heart [6] blood flow is
improved in diabetic patients.

In spite of these physiological functions, C-peptide is actually removed
from pharmaceutical preparations of insulin sold by drug companies when they
manufacture the synthetic human insulin that is in widescale clinical usage
today.

Here is another article which talks about how c-peptide might be useful in
type II diabetes as well as type I.

http://www.personalmd.com/news/a1997072407.shtml

C-peptide Reduces Diabetic Complications

NEW YORK, July 24 (Reuters) -- C-peptide, a chain of amino acids created as
a by-product of insulin synthesis, appears to prevent or reverse vascular
and nerve damage in diabetic rats, according to a study published in the
journal Science.

"These observations certainly raise the possibility that (C-peptide) might
be useful clinically in preventing the onset and even reversing some of the
(diabetic) complications in vessels and nerves," said Dr. Joseph Williamson,
professor of pathology at Washington University School of Medicine in St.
Louis, and lead researcher of the study.

Insulin is first synthesized in certain cells of the pancreas as one long
polypeptide (chain of amino acids), called proinsulin. After proinsulin
achieves a specific shape, or conformation, it is cleaved at precise points
to release the active form of insulin -- and C-peptide.

Levels of the peptide are known to be decreased in the blood of people with
insulin-dependent (type 1 diabetes). But C-peptide was thought to have no
biological role outside of assisting insulin synthesis. This new research
contradicts this view, suggesting that the peptide may help prevent or limit
blood vessel and nerve damage that can occur in diabetes.

According to the study, insulin and high doses of C-peptide reversed damage
to the blood vessels and nerves of diabetic rats. Specifically, blood
vessels became less leaky, preventing cholesterol and proteins from
depositing in the vessel walls, potentially leading to atherosclerosis.

The researchers also found that C-peptide treatment prevented a decrease in
the activity of the sodium-potassium pump -- an essential component of many
cell membranes responsible for maintaining normal cellular function,
especially nerve cells. Diabetic patients commonly exhibit decreased
activity of the sodium-potassium pump in certain tissues of the body.

Improvements in blood vessels and nerves were only observed with high doses
of C-peptide, suggesting that this therapy may help both type 1 and type 2
diabetics. Individuals with type 1 diabetes cannot synthesize insulin, or
create very little of it. Accordingly, they have very low levels of
C-peptide. On the other hand, individuals with type 2 diabetes can
synthesize normal levels of insulin, as well as C-peptide. But their disease
stems from an inability to use the insulin their bodies produce.

Williamson believes that high doses of C-peptide will work for both types of
diabetics because "if you have supra-normal glucose levels, you also need
supra-normal C-peptide levels to prevent the dysfunction caused by elevated
glucose." Furthermore, he suspects that with C-peptide treatment, diabetics
will no longer need to worry about maintaining absolutely normal glucose
levels in their blood to prevent these cardiovascular and neurologic
complications.

"I think what's very interesting here is that this is a small peptide that
was essentially thought to have no life after it performed its function in
facilitating insulin synthesis," he said. "It's remarkable that it turns out
to have such dramatic effects."

The researchers were equally surprised with their results when they tried to
determine just how C-peptide works. Molecules or proteins, like insulin for
example, usually produce their effects by binding to cellular receptors and
inducing cellular changes. Yet, the study revealed that C-peptide did not
produce its dramatic effects through the usual receptor-mediated model.

"Many people have reported various effects of C-peptide over the years, but
most investigators in the scientific community have not been very receptive
to those reports largely because no one has really ever been able to
demonstrate a receptor that was thought to be required for hormones or
peptides to have any effect," explained Williamson.

In the classical receptor-mediated model, a protein has a very specific
structure, or chiral form, which binds to a receptor equally specific for
that chiral form -- much like the way a key fits into a lock. However,
experiments using structural analogs of C-peptide were still capable of
preventing the cardiovascular and neural complications of diabetes
suggesting that C-peptide did not work through a chiral-sensitive receptor.

"(C-peptide) is interacting with cells through non-chiral mechanisms as
opposed to the classical key and lock, or ligand and receptor interactions,"
proposed Williamson. He theorizes that C-peptide may work by binding to cell
membranes and forming pores or channels which could normalize the disrupted
cellular functions induced by diabetes.

"The mechanism of action appears to be very novel, and further studies are
clearly needed to really understand exactly how its effects are mediated
after these novel interactions with the cell," Williamson commented.

The Centers for Disease Control and Prevention estimates that diabetics are
2 to 3 times more likely to die from blood vessel and heart complications
than other people. Some diabetics also exhibit various forms of
neuropathy -- an altered ability to sense stimuli such as vibration --  
caused by widespread nerve cell damage.

KC