BIO270H1 Lecture Notes - Lecture 5: Spiral Valve, Hydroxylation, Tight Junction

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Published on 31 Jan 2013
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Wednesday, November 25, 2009
BIO270 Lecture 5
-One of the points he wants to mention is that when he was a grad student & he started off as a reproduction
biologist, & when he first went to see his professor, he decided well what he really wants to work on are
steroids. Steroids are really cool, particularly the sex steroids. He said well yeah, they are really interesting,
but he should work on peptides instead. He did & then when he finished his doctorates, he had the
opportunity to do a post-doc in Texas to work on peptides & also steroid stuff as well. So when he got his
PhD, he was really enthusiastic, piled everything into his truck & drove from Vancouver to Austin. & he
got to the laboratory, & found it, the laboratory was really quite disappointing. There is a lesson in all of
this you should check where you’re going before you get there because it was a considerable investment
& when he got there it wasn’t really what he wanted to do, didn’t really like the person, so after 3 days he
went back, driving another 4500 km back to Vancouver. He was in a pretty depressed state about the whole
thing, he thought his whole career had gone down the tube, he wasn’t really sure what he was going to do
for the rest of his life. So he decided well maybe he’ll go back to Edmonton they had a possible position
there so he decided to cross the border from the US to Edmonton or to Alberta in the middle of January.
Now there is a little border crossing where they have like one person crossing a day & these guys, they are
really bored & so they pulled him over, so what’s going on? He said he went to Texas, didn’t like the job &
came back. They said wait, you drove 4500 km to the south part of Texas, then turned around & came
back? Prof said yeah, seems like the right thing to do. How long did it take you, they asked & he replied it
took 3 days to drive there & 3 days to drive back. They said you drove 4500 km in 3 days? Yes I did, he
replies His truck was loaded with every one of his belongings & it was absolutely full, he had a little
canopy on the back of it, everything was full. So he goes, what’s all this stuff back there? He said those are
his belongings & that he was planning to move down there. But you came back? Yeah I came back. He says
well I don’t know, I think we’re going to have to search the truck & he gets on the radio & says ‘Hey Bob,
we have 619 going on here, we’re going to have to search the truck’. Oh great. So he’s sitting there & the
guy is going through the glove compartment & he pulls out this little brown file. What is this? He says it’s a
chemical he needs for his experiments it was estradiol. Now when a biologist seizes estradiol, they have
this white powder, so the guy gets back on the radio again & he says we’re going to upgrade this to a 620.
The prof gets impounded & so does the truck, got put in the interrogation cell & they searched the entire
truck & said well we’re going to test this. Fine, test it. He goes away & the prof is in this cold interrogation
room for hours, & he comes back & says well, it’s negative on all of our tests – well yeah it probably would
be. He says well what is it? Prof says it’s a steroid. & this is right at the time when Ted Johnson was
indicted for steroid abuse. He says well gee, that’s even worse right now especially with all the press
everywhere. He gets all excited, he runs back & shouts Hey Bob, it’s a steroid. Another hour goes by, &
then he comes back again, gee whiz it’s not on our list, he says, holding this vial, what is it exactly? He
says it’s estradiol, it’s a sex steroid. He says ooh so if I wanted to get big muscles, I would take this? No, if
you want big breasts you would take this. So the rule is here to be careful what you take across the border.
He eventually got let go. He never went back to work on estradiol – maybe that’s because of that incident.
- Now we have a series of lectures on 3 topics which are all kind of
related. We’re going to start talking about glucose & energy, & then we’ll
go into the stress system, & then after that we’ll be talking about
digestion. So they form a nice little set & then in the last class we’re going
to be going into dieresis it’s complex so we have allotted 2 hours for
dieresis. Hopefully we’ll have time for review & give us some intel.
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- One of the themes we will see, we spent a lot of time talking about the
neuroendocrine circuits in reproduction, & he was talking to some
students today about that little bit of detail, but one of the things that we
may want to consider is that when we’re looking at these cycles, here’s
going to be some pattern associated.
- Many of the hormones that are released by the brain play a role in a lot
of these actions tend to be peptides or small proteins, & then they tend to
release things like steroids from the tissues & they can get that kind of
feedback. But it’s frequently the case that you get these different classes
& the different classes have a particular functional attribute based on the
structural elements & some of the chemical properties we spoke about
earlier.
- Now we used reproduction as a model with a fair amount of detail
because the endocrine loops, the neuroendocrine & endocrine loops which
lead to reproduction, are fairly complex. Hopefully we have the
understanding that it’s a loop, something communicates to something else
that then goes back & we have this big circle.
- We’ll see with many of these cycles, all of these will follow that. The
lectures today are going to reflect variations on that theme.
- We will start with glucose & energy metabolism b/c this is really the key
to many of the mechanisms that we talk about. So whatever you do, any
type of activity you do involves glucose & energy metabolism & this
basic mechanism has become under the control of the stress system as we
call it. So we’ll be introduced to this first.
- Chapter 3: Regulation of Glucose Metabolism. We’re going to kind of
gloss over this so we have the basic rudiments for glucose metabolism
the reality is it’s a huge field, the regulation of glucose & its implications
in diabetes for example is a major medical issue & a large chunk of the
University of Toronto is engaged in this kind of research. Depending on
which way you go you’ll have many opportunities to study this
mechanism in detail.
- Glucose follows a really wonderful homeostatic mechanism as we’ve
seen, so clearly if blood glucose is too low, the brain can’t function.
Glucose is one of the only molecules that the brain can use for energy; in
some cases it can use fatty acids but for almost everything it’s only
glucose it can use. If there is no glucose going into the brain then it causes
severe disruptions in terms of how the brain works. Clearly if the brain
doesn’t work, then nothing else works so low glucose is a big concern.
- You may know some people who are hypoglycaemic in which case the
glucose gets cleared very rapidly from their bloodstream & they go into a
kind of low glucose situation. Some of this can be quite dramatic. The prof
had a friend who he traveled through England & she gave him ten minutes
warning that suddenly she was getting low on glucose & while they were
looking for a sandwich for her to eat, she collapsed on the sidewalk so it
can be a major concern. Then there are others of us who can go for 3 days
without eating it doesn’t affect us that much so there is an incredible
amount of variability.
- By the same token, if blood glucose is too high, then the osmotic
balance of blood is disturbed as well & that throws a number of things out
of kilter, including all of the water & ion homeostasis as well which we’ll
talk about next class.
- There are 2 principle hormones we’ll be looking at: insulin & glucagon.
Insulin lowers blood glucose levels & glucagon increases blood glucose
levels. These two are obviously in opposition to each other & much of the
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understanding of the homeostasis of this can be based around the
homeostasis of these two hormones obviously there are others but if we
understand these basic components then we’re almost there.
- Both of them are secreted by the pancreases & there is a direct feedback
loop. Insulin will impinge on glucagon which will communicate back to
insulin.
- Now the pancreas, like all organs in the body, receives a number of
neural signals. Remember the autonomic nervous system so it’s getting
direct neural input & also it receives a number of hormonal signals.
What’s going on in the pancreas is dependent on the day to day needs &
the minute to minute needs. While you won’t necessarily be able to
perceive a need for glucose at the moment, it might build up slowly over
time so it won’t necessarily be a nervous stimulus you’re getting, it could
be an endocrine stimulus you’re getting so the pancreas has to be
associated with both it has to have the ability to perceive both sets of
signals.
- This is what we call an antagonistic paring where the hormones have
opposite effects. There are many cases where you have one hormone &
there is another hormone that does what seems to be virtually the
opposite. Neuropeptide Y & corticotrophin releasing factor in terms of
stress like that too. For this one it is a wonderfully studied system.
- So it looks kind of like this. So what happens when you eat, well several
things will happen. One of the first things that will happen is a rise in
blood glucose as everything gets broken down in the digestive system that,
we’ll talk about later today, will eventually lead to the absorbance of
glucose in the bloodstream & that will increase blood glucose.
- And blood glucose going up is perceived by the pancreas. The
pancreases then secretes insulin & insulin is the signal to say okay, now
that we’ve got all that increase in glucose, we have to get it into the cells
so insulin is associated with the transport of glucose into the cells. So
insulin is a large peptide hormone, it goes into the bloodstream & travels
throughout the body & it hits a number of target organs. They will
eventually uptake the glucose & then this will cause a decrease in blood
glucose & cause blood glucose levels to fall. When blood glucose levels
fall to a certain degree, then insulin will also decrease.
- It also does a couple of other things. Glucose receptors in the digestive
tract will also perceive the glucose & this will cause the release of another
hormone called cholecystokinin. CCK is also found in the brain – we used
to called it pancreatic cholecystokinin but then we found that it was in the
brain so now it’s the same peptide, the same hormone so we refer to it as
CCK. & it will also make its way to the pancreas so here are our endocrine
signals, this is our nervous signal here & metabolic pathway.
- Okay, now at the same time when you’re eating, there is a bolus of food
going through & there are a number of stretch receptors in there. That says
ah hah you’re eating something, so even if you were to eat something else
you couldn’t digest, that causes the distension of your stomach, then it will
still do this.
- In fact, some groups, in order to ward off hunger, what they would do is
they would tie really tight belts around their midsection & so if there was
a small amount of distension, then they immediately get the signal that
yeah, we’ve already got the food.
- Okay so then that is hitting the various integrating sections of the brain
& the mass communicating from the direct route to the pancreas & we
have this loop.
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