From:
sukiec@optonline.net
Date: 2006-10-10 16:50:56 UTC
Subject: [ferrethealth] RE: Insulinoma & Melatonin
To: ferrethealth@smartgroups.com
*IF* it is having a negative effect that would be on the blood glucose leve=
ls not on the adrenal disease, so the way to tell would be by monitoring th=
e blood glucose levels, BUT the number of ferret who have this effect of bl=
ood glucose may be small.
In some melatonin can possibly decrease cortisol which can decrease blood s=
ugar levels (There is a study on this on-going.), BUT it appears to play a =
part in an opposite aspect which may increase blood glucose, too. There ar=
e articles on cortisol which will answer why this is being investigated.
So, you can not replace the implant next time and see if the blood glucose =
does better, and people who have ferrets with either insulinoma or diabetes=
who are worried could try oral melatonin first with monitoring to see if t=
here is any effect in either direction and then use or not use depending on=
the effect in that individual.
It sounds like more of your concern right now is with a failure of the adre=
nal to respond to treatment. That would not be from the melatonin. =
Here are some things for you to consider: =
1. The growth may be malignant in which case the chances of it responding =
to these medications is lowered.
2. The ferret may need a larger dose of Lupron
3. You may be using the daily Lupron instead of the Lupron Depot. There w=
as a place in the midwest which sold very inexpensive Lupron "for monthly u=
se" but it was daily Lupron. Daily Lupron has the capacity to worsen the s=
ituation. See:
http://www.miamiferret.org/fhc/24hr_lupron.htm
If I read these right there are different pancreatic effects that can be op=
posing mentioned in these:
START QUOTES
J Pineal Res. 2006 Mar;40(2):184-91.
Links
Parallel signaling pathways of melatonin in the pancreatic beta-cell.
Peschke E, Bach AG, Muhlbauer E.
Institute of Anatomy and Cell Biology, Martin Luther University Halle-Witte=
nberg, Halle/Saale, Germany. elmar.peschke@medizin.uni-halle.de
Previous results demonstrated that melatonin inhibits cAMP production and s=
timulates IP(3) liberation in rat insulinoma INS1 cells, a model for the pa=
ncreatic beta-cell. This study addresses the impact of melatonin on insulin=
release. Insulin, cAMP and IP(3) levels of INS1 cells in a superfusion sys=
tem were measured. Initially, forskolin was used to stimulate cAMP and subs=
equently insulin release. Incubation of forskolin (5 micromol/L)-stimulated=
cells with melatonin (100 nmol/L) inhibited cAMP and insulin levels (down =
to 60% of insulin and cAMP release). The G(i)alpha-protein-inhibitor pertus=
sis toxin (PTX) was used to distinguish between the G(i)alpha-dependent cAM=
P pathway and the G(i)alpha-independent IP(3) pathway. In our experiments w=
e employed a specific stimulation pattern to prove proper inhibition of G(i=
)alpha-proteins by PTX. In INS1 cells incubated with 250 ng/mL PTX for 24 h=
r, melatonin was no longer able to inhibit the forskolin-induced cAMP and i=
nsulin release. In a study, carbachol was used to stimulate IP(3) and subse=
quently insulin release. Surprisingly, incubation of carbachol (300 micromo=
l/L)-stimulated cells with melatonin (100 nmol/L) inhibited insulin release=
(down to 75% of insulin release). Finally, in PTX-incubated INS1 cells, me=
latonin (100 nmol/L) increased carbachol (300 micromol/L)-induced insulin r=
elease (up to 124% of insulin release). In conclusion, we found that the me=
latonin MT(1)-receptor on pancreatic beta-cells is coupled to parallel sign=
aling pathways, with opposite influences on insulin secretion. The cAMP- an=
d subsequently insulin-inhibiting signaling pathway involves PTX-sensitive =
G(i)alpha-proteins and is predominant in terms of insulin release.
PMID: 16441556 [PubMed - indexed for MEDLINE]
J Pineal Res. 2006 Mar;40(2):135-43.
Links
Diabetic Goto Kakizaki rats as well as type 2 diabetic patients show a decr=
eased diurnal serum melatonin level and an increased pancreatic melatonin-r=
eceptor status.
Peschke E, Frese T, Chankiewitz E, Peschke D, Preiss U, Schneyer U, Spesser=
t R, Muhlbauer E.
Institute of Anatomy and Cell Biology, Martin Luther University Halle-Witte=
nberg, Halle/Saale, Germany. elmar.peschke@medzin.uni-halle.de
There are functional inter-relationships between the beta cells of the endo=
crine pancreas and the pineal gland, where the synchronizing circadian mole=
cule melatonin originates. The aim of this study was to elucidate a putativ=
e interaction between insulin and melatonin in diabetic patients and a diab=
etic rat model. We analyzed glucose, insulin, and melatonin levels of type =
2 patients, as well as type 2 diabetic Goto Kakizaki (GK) rats by radioimmu=
noassay. Expression of pancreatic melatonin and pineal insulin receptors, a=
s well as arylalkylamine-N-acetyltransferase (AANAT), was determined by rea=
l-time reverse transcriptase polymerase chain reaction (RT-PCR). The AANAT =
enzyme activity was measured in pineal homogenates. Diabetic patients showe=
d a decrease in melatonin levels, while in the pancreas of GK rats an upreg=
ulation of the melatonin-receptor mRNA was determined. The pancreatic islet=
s of GK rats showed expression of the mRNA for the pancreatic melatonin (MT=
1) receptor, which had previously been identified in rats and insulinoma (I=
NS1) cells. Besides their presence in animal cells, the MT1-receptor transc=
ript was also detected in human pancreas by RT-PCR. Whereas the rat pancrea=
tic mRNA expression of the MT1-receptor was significantly increased, the ac=
tivity of the pineal AANAT enzyme was reduced. The latter observation was i=
n accordance with plasma melatonin levels. The insulin-receptor mRNA of the=
pineal gland was found to be reduced in GK rats. Our observations suggest =
a functional inter-relationship between melatonin and insulin, and may indi=
cate a reduction of melatonin in the genesis of diabetes.
PMID: 16441550 [PubMed - indexed for MEDLINE]
J Pineal Res. 2005 Oct;39(3):316-23.
? Links
Melatonin stimulates inositol-1,4,5-trisphosphate and Ca2+ release from INS=
1 insulinoma cells.
Bach AG, Wolgast S, Muhlbauer E, Peschke E.
Institute of Anatomy and Cell Biology, Martin Luther University Halle-Witte=
nberg, Halle/Saale, Germany.
The effects of melatonin in mammalian cells are exerted via specific recept=
ors or are related to its free radical scavenging activity. It has previous=
ly been reported that melatonin inhibits insulin secretion in the pancreati=
c islets of the rat and in rat insulinoma INS1 cells via Gi-protein-coupled=
MT1 receptors and the cyclic adenosine 3',5'-monophosphate pathway. Howeve=
r, the inositol-1,4,5-trisphosphate (IP3) pathway is involved in the insuli=
n secretory response as well, and the melatonin signal may play a part in i=
ts regulation. This paper addresses the involvement of the second messenger=
s IP3 and intracellular Ca2+ ([Ca2+]i) in the signalling cascade of melaton=
in in the rat insulinoma INS1 cell, a model for the pancreatic beta-cell. F=
or this purpose melatonin at concentrations ranging from 1 to 100 nmol/L, c=
arbachol and the nonselective melatonin receptor antagonist luzindole were =
used to stimulate INS1 cell batches, followed by an IP3-mass assay and Ca2+=
imaging. Molecular biological studies relating to the mRNA of IP3 receptor=
(IP3R) subtypes and their relative abundance in INS1 cells showed expressi=
on of IP3R-1, IP3R-2 and IP3R-3 mRNA. In conclusion, we found that in rat i=
nsulinoma INS1 cells there is a dose-dependent stimulation of IP3 release b=
y melatonin, which is accompanied by a likewise transient increase in [Ca2+=
]i concentrations. The melatonin effect observed mimics carbachol action. I=
t can be abolished by 30 micromol/L luzindole and is sustained in Ca2+-free=
medium, suggesting a mechanism that includes the depletion of Ca2+ from in=
tracellular stores.
PMID: 16150114 [PubMed - indexed for MEDLINE]
END QUOTES
The whole question of the effects of melatonin on blood glucose are very ne=
w ones and involve exceedingly complex endocrinological interactions that a=
re ****still poorly understood**** in a number of situations. The only cur=
e for that chunk of ignorance right now will be well designed, careful stud=
y after well designed, careful study and the time for them to happen. =
Until then people who worry can try the oral melatonin first and monitor WH=
EN insulinoma or diabetes also exists in the ferret being treated for adren=
al disease.
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