From:
sukiec@optonline.net
Date: 2006-05-24 19:05:57 UTC
Subject: [ferrethealth] pancreas, adrenal
To: ferrethealth@smartgroups.com
I wonder if any of the subsets they learn might turn out to help understand=
any aspects of insulinoma, and if perhaps future meds that inhibit the enz=
yme, glutamate dehydrogenase, may prove useful in treating ferret insulinom=
a?
There are so many pancreatic mysteries being unraveled in the last couple o=
f years, with a great many unexpected things found, for example last year t=
he estradiol receptor discovery.
Cool new adrenal discoveries are coming about, too, for example, that the a=
drenal appears to contain a secondary internal clock rather like the brain =
one, and that other organs also may. This may evenutally turn out be conne=
cted to the melatonin communications going on. (See press release at the b=
ottom of the post.)
Endocrinology is still mostly a mystery, but new things are being discovere=
d all the time. Heck, it wasn't even realized until a few years ago that f=
at acts as a hormonal tissue.
These are released for public consumption from PubMed and Eurkalert!:
QUOTES
Public release date: 24-May-2006
Contact: Nicole Kresge
nkresge@asbmb.org
301-634-7415
American Society for Biochemistry and Molecular Biology
Enzyme defect leads to hyperinsulinism
Bethesda, MD =96 A recent study in the Journal of Biological Chemistry conf=
irms that mutations in an enzyme called glutamate dehydrogenase can cause c=
ongenital hyperinsulinism. The research appears as the "Paper of the Week" =
in the June 2 issue of the Journal of Biological Chemistry, an American Soc=
iety for Biochemistry and Molecular Biology journal.
Congenital hyperinsulinism is a group of genetic disorders that cause hypog=
lycemia in infants and children. "The hypoglycemia is quite dangerous and c=
an cause seizures and permanent brain damage if not promptly detected and t=
reated," says Charles A. Stanley, of the Children's Hospital of Philadelphi=
a. "In its various forms, congenital hyperinsulinism is the most common and=
most difficult cause of hypoglycemia in young infants."
The majority of cases of congenital hyperinsulinism appear to be due to def=
ects in insulin secretion by pancreatic cells. Currently, it is thought tha=
t mutations in any of four different genes can cause the disorder. One of t=
hese genes codes for an enzyme called glutamate dehydrogenase. This enzyme =
is stimulated by the amino acid leucine, meaning that protein meals that co=
ntain leucine lead to activation of glutamate dehydrogenase, which in turn =
triggers the release of insulin from pancreatic cells.
"The glutamate dehydrogenase mutations that cause hyperinsulinism are amino=
acid mis-sense mutations that impair the sensitivity of the enzyme to inhi=
bition," explains Stanley. "As a result, glutamate dehydrogenase enzyme act=
ivity cannot be turned off and this leads to excessive release of insulin a=
nd hypoglycemia."
In order to understand how amino acids stimulate insulin and the role of gl=
utamate dehydrogenase in this pathway, Stanley and his colleagues at the Un=
iversity of Pennsylvania generated transgenic mice that had a mutation in t=
heir gene for glutamate dehydrogenase. The resulting mice had hypoglycemia,=
confirming that the mutation can cause disease.
"By over-expressing the mutant form of glutamate dehydrogenase in pancreati=
c islets, we were able to show that increased glutamate dehydrogenase enzym=
e activity leads to increased insulin release in the presence of amino acid=
s," says Stanley. "These results were necessary to demonstrate that the mut=
ations of glutamate dehydrogenase which we have found in patients are indee=
d responsible for causing disease. In addition, they provide an understandi=
ng of precisely how amino acids derived from dietary protein exert their ef=
fects of controlling insulin."
The results of this study have potential for many therapeutic and diagnosti=
c applications according to Stanley. "The results firmly establish how glut=
amate dehydrogenase mutations cause hyperinsulinism and provide potential t=
argets for development of new drugs, such as inhibitors of the enzyme, whic=
h might be used to treat patients. The results also provide support for usi=
ng genetic mutation analysis of glutamate dehydrogenase to help diagnose ch=
ildren with hyperinsulinism. Broader implications of the results include th=
e possibility that glutamate dehydrogenase or enzymes in the pathways of am=
ino acid stimulated insulin secretion could serve as targets for drugs to t=
reat diabetes," concludes Stanley.
###
The Journal of Biological Chemistry's Papers of the Week is an online featu=
re which highlights the top one percent of papers received by the journal. =
Brief summaries of the papers and explanations of why they were selected fo=
r this honor can be accessed directly from the home page of the Journal of =
Biological Chemistry online at www.jbc.org.
The American Society for Biochemistry and Molecular Biology (ASBMB) is a no=
nprofit scientific and educational organization with over 11,000 members in=
the United States and internationally. Most members teach and conduct rese=
arch at colleges and universities. Others conduct research in various gover=
nment laboratories, nonprofit research institutions, and industry.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus =
of the Federation of American Societies for Experimental Biology. The Socie=
ty's primary purpose is to advance the sciences of biochemistry and molecul=
ar biology through its publications, the Journal of Biological Chemistry, t=
he Journal of Lipid Research, Molecular and Cellular Proteomics, and Bioche=
mistry and Molecular Biology Education, and the holding of scientific meeti=
ngs.
For more information about ASBMB, see the Society's website at www.asbmb.or=
g
---
Horm Res. 2006 May 19;66(1):43-44 [Epub ahead of print]
Fluorine-18 L-3,4-Dihydroxyphenylalanine Positron Emission Tomography: Impr=
oving Surgery and Outcome in Focal Hyperinsulinism. Commentary to Mohnike e=
t al.: Proposal for a Standardized Protocol for F-DOPA-PET (PET/CT) in Cong=
enital Hyperinsulinism (Horm Res 2006;66:40-42).
Shield JP.
Bristol Royal Hospital for Children, University of Bristol, Bristol, UK.
PMID: 16710095 [PubMed - as supplied by publisher]
---
Public release date: 22-May-2006
[ Print Article | E-mail Article | Close Window ]
Contact: Jim Newman
newmanj@ohsu.edu
503-494-8231
Oregon Health & Science University
OHSU primate center research suggests multiple 'body clocks'
PORTLAND, Ore. =96 Research conducted at Oregon Health & Science University=
suggests that contrary to popular belief, the body has more than one "body=
clock." The previously known master body clock resides in a part of the br=
ain called the suprachiasmatic nucleus (SCN). Researchers at OHSU's Oregon =
National Primate Research Center (ONPRC) have now revealed the existence of=
a secondary clock-like mechanism associated with the adrenal gland. The re=
search also suggests a high likelihood that additional clocks exist in the =
body. The study results are printed in the current edition of the journal M=
olecular Endocrinology.
"We're all familiar with the idea that the body has a master clock that con=
trols sleep-wake cycles. In fact, most of us have witnessed the impacts of =
this clock in the form of jet lag where it takes the body a number of days =
to adjust to a new time schedule following a long flight," explained Henryk=
Urbanski, Ph.D., senior author of the study and a senior scientist at ONPR=
C. "Our latest research suggests that a separate but likely related clock r=
esides in the adrenal gland. The adrenal gland is involved in several impor=
tant body functions, such as body temperature regulation, metabolism, mood,=
stress response and reproduction. The research also suggests that other pe=
ripheral clocks reside throughout the body and that these clocks are perhap=
s interconnected."
To conduct the research, scientists studied adrenal gland function in rhesu=
s macaque monkeys which is very similar to human adrenal gland function. Sp=
ecifically, researchers measured gene expression in the adrenal gland of mo=
nkeys during a 24-hour period (six times a day, four-hour intervals). In an=
alyzing this information, researchers identified 322 genes in the adrenal g=
land with functions that varied rhythmically over a 24-hour period, meaning=
that each gene's function peaked and diminished at the same time each day.=
Interestingly, the scientists also noted that a subgroup of these 322 gene=
s also exist in the SCN =96 the home of the body's master body clock. This =
suggests that the adrenal gland has its own timing mechanism that is relate=
d to, but separate from, the SCN body clock.
"Of course, different genes peaked in function at different times of the da=
y," explained Dario Lemos, an OHSU graduate student in the Urbanski lab and=
first author of the study. "For instance, genes controlling catecholamine =
secretion were more active in the day with function greatly decreasing at n=
ight. Catecholamines are involved in many important body functions, such as=
stress and mood."
This research provides important new information regarding the complex, rhy=
thmic, 24-hour functions of the body. The research may also impact current =
therapies for a variety of diseases. For instance, data gathered in this st=
udy and future studies may suggest that certain therapies be delivered at c=
ertain times to synchronize with normal body functions controlled by body c=
locks.
"One example is testosterone replacement, a common treatment for certain di=
sorders in males such as sexual dysfunction and depression," explained Urba=
nski. "Patients receiving testosterone late in the day often complain of sl=
eep loss. This is likely due to the fact that in healthy people, testostero=
ne levels are lower in the afternoon and evening. As more data is gathered =
about body clock functions in our lab and others, we will likely learn of a=
specific window of time during the day where testosterone therapy is effec=
tive, but less disruptive for patients."
###
The ONPRC is a registered research institution, inspected regularly by the =
United States Department of Agriculture. It operates in compliance with the=
Animal Welfare Act and has an assurance of regulatory compliance on file w=
ith the National Institutes of Health. The ONPRC also participates in the v=
oluntary accreditation program overseen by the Association for Assessment a=
nd Accreditation of Laboratory Animal Care International.
END QUOTES
-- Sukie (not a vet, and not speaking for any of the below in my private po=
sts)
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