|
Novel approaches related
to other pancreatic hormones
Though the focus has inevitably been on insulin itself, it
will be recalled that the pancreas secretes several hormones
as well as insulin. These include glucagon and a substance
called amylin, another peptide, this time composed of 37 amino
acids. Evidence has been built up over the last decade that
links amylin to diabetes. Firstly, amylin secretion follows
the same pattern as insulin, with peaks at mealtimes – in
fact, amylin is packaged together with insulin in the beta
cell granules. Secondly, it has been shown that it inhibits
the appearance of glucose in the plasma while insulin stimulates
its disappearance. Thirdly, amylin appears to be deficient
in people with type I diabetes and partially deficient in
those with type 2 diabetes. Fourthly, its secretion rises
following glucose administration.
Natural amylin was found not to dissolve readily and to stick
to itself – both properties that made it unsuitable for a
medicine. Amylin Pharmaceuticals looked at variations on the
amylin molecule and as a result developed pramlintide, which
has three different amino acids compared to the natural material.
With further development, pramlintide could play a useful
role in diabetes care.
Another hormone of interest is called GLP-1 (glucagon-like
peptide-1). It is released from the gut in response to food
and binds to receptors on the beta cells, where it stimulates
insulin release. Eli Lilly and Company and Bayer both have
research activities in this area but, so far, no compounds
that have reached man. Novo Nordisk has GLP-1(7-36) in early
clinical trials and has shown that it reduces blood glucose
levels after meals when injected into people with type 2 diabetes.
Amylin Pharmaceuticals is also studying a compound (AC 2993,
Exendin-4) which was isolated from the venom of poisonous
lizards found in Mexico and Arizona. It has considerable structural
similarities to GLP-1 and has glucose-lowering actions similar
to insulin. It is currently in Phase I trials and has shown
greater potency than GLP-1 itself.
|
