Message Number: FHL12242 | New FHL Archives Search

From: Sukie Crandall
Date: 2010-09-19 18:51:21 UTC
Subject: [ferrethealth] Okay, now THIS press release might have fascinating implications
To: fhl <ferrethealth@yahoogroups.com>, Ferret Mailing List <ferret-l@LISTSERV.FERRETMAILINGLIST.ORG>

Why?

Partly because with domestic ferrets, domestic cats, and domestic dogs
we are talking about animals who were recently nocturnal (with mostly
crepuscular peak activity -- meaning dawn and dusk -- and burrow
darkness otherwise for polecats) which people have been shifting to
being largely diurnal, so the question arises of how much effect that
has on their liver and pancreatic functions, and measuring this
protein and comparing it to that of wild polecats or zoo polecats kept
in natural lighting and other living conditions might be useful.

More why?:

Partly because we already know that light exposure reduces melatonin
production. (The blue wavelength range is the worst, while the
second worst is the green wavelength range -- used in many equipment
lights and night lights. The least disruptive is amber colored
lighting (yellowy-orange) so prefer any type of light that looks amber
at dusk and afterward for ferrets, and if you can ***safely*** cover
or block the blue or green then do so.) Now, too little melatonin
production increases luteinizing hormone production. Increased
luteinizing hormone production is the trigger for adrenal tumors. OPPS!

Individuals with their biological clocks off resulting in too much
light exposure for their species are going to produce too little
melatonin. (Aging also reduces the amount of melatonin that a body
can naturally make.)

Press Release:
> University of California -- San Diego
> Biologists discover biochemical link between biological clock and
> diabetes
> Biologists have found that a key protein that regulates the
> biological clocks of mammals also regulates glucose production in
> the liver and that altering the levels of this protein can improve
> the health of diabetic mice.
>
> Their discovery, detailed in this week's advanced online publication
> of the journal Nature Medicine, provides an entirely new biochemical
> approach for scientists to develop treatments for obesity and type 2
> diabetes. It also raises the interesting possibility that some of
> the rise in diabetes in the U.S. and other major industrialized
> countries could be a consequence of disturbances in sleep-wake
> cycles from our increasingly around-the-clock lifestyles.
>
> "We know that mice that don't have good biological clocks tend to
> develop diabetes and obesity," said Steve Kay, Dean of the Division
> of Biological Sciences at UC San Diego and one of the lead authors
> of the research study. "And we know that mice that have developed
> diabetes and obesity tend not to have very good biological clocks.
> This reciprocal relationship between circadian rhythm and the
> maintenance of a constant supply of glucose in the body had been
> known for some time. But what we found that's so significant is that
> a particular biological clock protein, cryptochrome, is actually
> regulating how the hormone that regulates glucose production in the
> liver works in a very specific way."
>
> "We used to think that our metabolism was regulated primarily by
> hormones that are released from the pancreas during fasting or
> feeding. This work shows that the biological clock determines how
> well these hormones work to regulate metabolism," says Marc
> Montminy, a professor in the Clayton Foundation Laboratories for
> Peptide Biology at the Salk Institute for Biological Studies. "The
> study may explain why shift workers, whose biological clocks are
> often out of kilter, also have a greater risk of developing obesity
> and insulin resistance."
>
> Cryptochrome was first discovered by scientists as a key protein
> regulating the biological clocks of plants. It was later found to
> have the same function in fruit flies and mammals. But its role in
> regulating glucose production in the liver came as a complete
> surprise to the UCSD and Salk team, which included scientists from
> the Genomics Institute of the Novartis Research Foundation in San
> Diego, the University of Memphis and the Chinese Academy of Sciences
> in Shanghai.
>
> "What was incredibly surprising is that cryptochrome has a new
> function that nobody had predicted," said Eric Zhang, the first
> author of the study and a researcher in Kay's UCSD laboratory.
> "Until now, cryptochrome had been known as a protein inside the
> nucleus of mammalian cells that switches genes on and off in a
> rhythmic way. What we showed was that cryptochrome has a role
> outside the nucleus as well."
>
> That additional function of cryptochrome in mammalian cells, the
> scientists discovered, is to regulate a process known as
> "gluconeogenesis," in which our bodies supply a constant stream of
> glucose to keep our brain and the rest of our organs and cells
> functioning. When we're awake and eating, sufficient glucose is
> supplied to our bloodstream. But when we're asleep or fasting,
> glucose needs to be synthesized from the glycogen stored in our
> liver to keep our glucose levels up.
>
> "That is how our energy metabolism evolved to function in concert
> with our diurnal activity, or in the case of the mice, their
> nocturnal activity," said Kay. "This molecular mechanism involving
> cryptochrome presumably evolved to coordinate our energy metabolism
> with our daily activity and feeding levels. So could some instances
> of diabetes be the result of a faulty circadian clock? And if that's
> the case, can we find ways of fixing the clock to treat this
> disease? Such an approach would be a whole new way of thinking about
> how to develop new treatments for diabetes."
>
> In their study, the scientists found evidence that such an approach
> would be feasible. "Our experiments show very nicely that modulating
> cryptochrome levels in the liver of mice can actually give diabetic
> animals a benefit," Kay added.
>
> The researchers discovered cryptochrome's role in gluconeogenesis
> while studying how a signaling molecule known as cyclic AMP
> interacted with the biological clock.
>
> "It had been known for some time now that there was a connection
> between cyclic AMP signaling and circadian rhythm regulation and
> that's where we started," said Kay, "by asking the question: How are
> those two connected?"
>
> Zhang and his UCSD colleagues conducted a series of experiments that
> found that the production of the next step after cyclic AMP, a
> protein called Creb, ebbed and flowed rhythmically in the livers of
> mice. That led the scientists to their initial discovery that
> cryptochrome was regulating the production of Creb in the liver.
>
> In their studies with fasting and insulin-resistant mice at the Salk
> Institute, the scientists found that cryptochrome was regulating how
> the hormone glucagon, which controls gluconeogenesis, works in a
> very specific way. By controlling the production of cyclic AMP,
> crytochrome regulates the activity of Creb in the liver. In this
> way, the production of glucose in the liver is tied through our
> daily eating, sleeping and fasting activities through the biological
> clock.
>
> The scientists say their discovery may open up a whole new area of
> research into how cryptochrome may be regulating other cell
> functions outside the nucleus.
>
> "There's a wide role that the biological clock may be playing in
> influencing other hormones, not just glucagon, that are important
> for metabolism," said Kay.
>
> In addition, studies on human populations have found links between
> disturbances in the biological clock, such as shift work and chronic
> jet lag, and the propensity to develop certain kinds of cancers as
> well as diabetes. Because of this, the scientists plan to continue
> their research into cryptochrome, looking for compounds that may
> enhance or diminish the activity of this critical biological clock
> protein
>
> ###The research was funded by grants from the National Institutes of
> Health. Other co-authors of the paper include Tsuyoshi Hirota,
> Dmitri A Nusinow, Pagkapol Pongsawakul and Andrew Liu of UCSD's
> Division of Biological Sciences; David Brenner and Yuzo Kodama of
> the UCSD School of Medicine; Yi Liu, Renaud Dentin and Severine
> Landais of The Salk Institute; and Xiujie Sun of the Chinese Academy
> of Sciences.
>

This appears to be a different but related very recent study on
cryptochrome:
http://www.biomedcentral.com/content/pdf/1471-2199-11-69.pdf
That is not the final pdf version, but rather a provisional one
because it is a brand new publication so it might disappear or
disappear on and off depending on how they assign URLs.

Abstract:
http://www.ncbi.nlm.nih.gov/pubmed/20840750

A bit more:
http://www.biomedcentral.com/1471-2199/11/69

Oh, and there is currently quite a bit of work in multiple species
that ties eating a lot (the food type did not matter) to increased LH
production, while LH production goes down if the food amount returns
to a better level for the species. See PubMed or for summaries:
http://ferrethealth.org/archive/FHL12184
and
http://ferrethealth.org/archive/FHL12185

(There is some recent preliminary human food work that indicates that
due to being processed, some types of processed foods are digested
more efficiently so it might be easier to become over-weight or to
over-eat with some types of processed food, indicating the extra
physical activity becomes even more important (says she who is
currently slowed down from thyroid problems). This should not be a
complete surprise; it is already very ( very, very, very, very , very)
well documented that even just cooking can "pre-digest" foods which is
why cooked foods break down more efficiently in the body, and that is
so for both animal origin foods and plant foods.)

This recent work also has possible implications for both pancreatic
and adrenal health of ferrets:

http://www.cell.com/cell-metabolism/abstract/S1550-4131%2810%2900270-6

http://www.sciencenews.org/view/generic/id/63109/title/Study_clarifies_obes=
ity-infertility_link

Notice that the pituitary does not become insulin-resistant. That has
cascading implications for the mechanisms involved in a whole range of
endocrinological health problems, since it tosses out a number of
earlier hypotheses in any species for which that is the case.

A new study in mice shows that the pituitary gland, which helps
> regulate the release of fertility-associated hormones, remains
> sensitive to insulin. But in obese mice, insulin's constant
> signaling to release the fertility hormones leads to an
> overabundance of those hormones

LH is among the hormones increased in the mice (but LH production in
such a situation has to be compared across species). Again, LH is the
trigger for adrenal growths in ferrets.

Sukie (not a vet)

Recommended ferret health links:
http://pets.groups.yahoo.com/group/ferrethealth/
http://ferrethealth.org/archive/
http://www.afip.org/ferrets/index.html
http://www.miamiferret.org/
http://www.ferrethealth.msu.edu/
http://www.ferretcongress.org/
http://www.trifl.org/index.shtml
http://homepage.mac.com/sukie/sukiesferretlinks.html
all ferret topics:
http://listserv.ferretmailinglist.org/archives/ferret-search.html

"All hail the procrastinators for they shall rule the world tomorrow."
(2010, Steve Crandall)


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