Bigging up the Danes

For my sins, from 2013 to 2020 inclusive, I taught Human Physiology to 1st year Pharm tech students. My only qualifications for doing this were a) I have a body b) nobody else wanted to do it. I inherited a bunch of PPT slides, the Learning Outcomes and 30-something students almost all of whom were women. Don't know about the students, but I learned a lot. Human Phys is all about homeostasis - keeping the various systems of the body in trim to quite fine tolerances. You know this: over-heating by even 1 or 2 °C makes you feel like crap. If your blood pressure goes up a little, you're likely to blow an aneurism or have a stroke . . . goes down a little and the blood will rush from your head and you'll collapse to the floor. Your bod keeps to the set-points of tolerance with a complex system of checks & balances = belt & braces = redundancy. My fave hormone Vasopressin squeezes the smooth muscle AND reduces water-loss in the kidneys both effects geeing up the blood pressure.

I put it to you that 9/10 people stopped on the street will have heard of insulin and have some idea about what it does [regulates circulating blood sugar). otoh those same 9/10 will nope out when asked about glucagon. But you absolutely need them both and the receptors to which they bind to effect their magic on each cell of the body. I've shared my discoveries about glucagon several times in The Blob. TIL that, like a lot of proteins /peptides, the hormone glucagon is derived from a rather larger "pro"-peptide which is 180 amino acids in length. After translation this longer protein is enzymatically cleaved into three quite similar peptides, at least two of which are biochemically active: a) glucagon b) GLP-1 = glucagon-like peptide #1 and b) GLP-2. This shows that three copies of the active bit 'were created' in evolutionary time and have subsequently been free to mutate and acquire a wider range of specific functions.

GLUC      ------HSQGTFTSDYSKYLDSRRAQDFVQWLMNT----
GLP1      HDEFERHAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG--
OZEM            HxEGTFTSDVSSYLEGQAAxDFIAWLVRGRG
GLP2      ------HADGSFSDEMNTILDNLAARDFINWLIQTKITD
                *::*:*:.: .. *:.  *::*: **:: 

These peptide hormones are at nothing unless and until they dock with a specific receptor sitting in the membrane of all the cells in the body. GLP1 binds to <surprise!> the GLP1 receptor which starts a cascade of internal reactions to do with glucose metabolism. These reactions may be wide-ranging in different tissues (as with vasopressin == ADH anti-diuretic hormone two paragraphs up). One known effect is the inhibition of glucagon. That will prevent free glucose circulating which means that insulin won't have to work so hard to keep glucose levels at their set point. and that would be good for diabetics. A few years ago boffins looked at the sequence of GLP1 and thought "target". They modified the sequence of GLP1 [see alignment of the amino acids in colour above] to create semaglutide which really binds the GLP1-receptor.

Novo Nordisk the Danish Megapharm which owns the IP on Semaglutide = Ozempic = Wegovy is now the biggest corporation in the EU with a market cap of $500 billion. Ozempic is the company's golden goose and is responsible for pretty much all of Denmark's economic growth during Coronarama. If you'd bought shares in Novo Nordisk  5 years ago you would have had a 5x return on your investment. Ozemic featured on RTE on 4th March b/c World Obesity Day.

Ozempic hopped through all the regulatory hoops as an effective treatment for type-II (late-onset) diabetes because of it's domino effect on the regulation of blood-sugar levels. Later on it was realised that Ozempic was effective in helping ppl with obesity shed a few kilos. It was therefore widely prescribed for that condition. In 2021, the FDA approved this use of semaglutide, under the trade-name Wegovy. 

It turns out that Novo Nordisk, even with outsourcing production to several other facilities, cannot produce enough Ozempic to satisfy the market in diabetes and obesity. Part of the problem is that this drug is being widely prescribed 'off-label' to reasonably healthy people who desire to trim their midriff to look good [and maybe pull their cousin's BFF]? at an up-coming family wedding. That's how markets work: well rich people can obtain a scarce resource - because money - and can insulate their conscience from the effect this choice has on really sick poor people on the other side of the tracks. And social media influencers? They can eat their own brittle!