Message Number: FHL5003 | New FHL Archives Search
From: "Sukie Crandall"
Date: 2008-05-23 19:33:33 UTC
Subject: [ferrethealth] Re: question for vets and members

Sorry about being rushed and responding for the wrong med.=20
In relation to melatonin and ferret pancreatic functions: there
is NO data on that yet. That dearth of information is not likely
to change in the short term. There are actually opposing
functions that melatonin has been noticed being involved in for
the pancreas and some vet have found insulinoma worsening
when there is an implant while some others have seen it lessening
and still others have not noticed a change. I have never encountered
anything linking it to a massive change, though, so more likely it
was the onset of insulin-resistant diabetes.

Some recent work (non-ferret so may not have a bearing for them)
does NOT look to me from skimming like the melatonin was likely
to be a trigger but I am not an endocrinologist nor a vet:

J Pineal Res. 2008 Jan;44(1):52-6.
Melatonin-insulin interactions in patients with metabolic syndrome.
Robeva R, Kirilov G, Tomova A, Kumanov P.
Clinical Center of Endocrinology, Medical University Sofia, Sofia, Bulgaria=

Metabolic syndrome (MS) as a group of risk factors is strongly
associated with diabetes type 2 and cardiovascular disease. Insulin
resistance plays a key role in the pathogenesis of MS. Recent studies
have shown that melatonin may influence insulin secretion and glucose
homeostasis. Therefore, the present study analyzed the relationships
between the melatonin and the insulin in patients with MS and controls.
The melatonin rhythm, insulin and lipid levels were studied in 40
subjects (21 patients and 19 controls) in reproductive age. The night
melatonin-insulin ratio was correlated negatively with low-density
lipoprotein cholesterol (r =3D -0.370, p =3D 0.024) and total cholesterol
(r =3D -0.348, p =3D 0.030), and positively with high-density lipoprotein
cholesterol levels (r =3D +0.414, p =3D 0.010). Night-time melatonin levels=

were related to night-time insulin concentrations (r =3D +0.313, p =3D
0.049). The correlation was pronounced in patients with MS (r =3D +0.640,
p =3D 0.002), but did not reach statistical significance in controls (P > 0=
In the patients with MS unlike the controls the night-day melatonin
difference (%) correlated negatively with the fasting glucose (r =3D -0.494=
p =3D 0.023) and positively to daily insulin (r =3D +0.536, p =3D 0.012). O=
results show that melatonin-insulin interactions may exist in patients
with MS, as well as relationships between melatonin-insulin ratio and
the lipid profile. Pineal disturbances could influence the pathogenesis
and the phenotype variations of the MS. Larger studies are needed to
confirm or reject this hypothesis and to clarify the role of the melatonin=

in the metabolic disturbances.

J Pineal Res. 2008 Jan;44(1):26-40.
Melatonin, endocrine pancreas and diabetes.
Peschke E.
Institute of Anatomy and Cell Biology, Martin Luther University Halle-Witte=

Melatonin influences insulin secretion both in vivo and in vitro. (i)
The effects are MT(1)-and MT(2)-receptor-mediated. (ii) They are
specific, high-affinity, pertussis-toxin-sensitive, G(i)-protein-coupled,
leading to inhibition of the cAMP-pathway and decrease of insulin
release. [Correction added after online publication 4 December 2007:
in the preceding sentence, 'increase of insulin release' was changed
to 'decrease of insulin release'.] Furthermore, melatonin inhibits the
cGMP-pathway, possibly mediated by MT(2) receptors. In this way,
melatonin likely inhibits insulin release. A third system, the IP(3)-
pathway, is mediated by G(q)-proteins, phospholipase C and IP(3),
which mobilize Ca(2+) from intracellular stores, with a resultant
increase in insulin. (iii) Insulin secretion in vivo, as well as from
isolated islets, exhibits a circadian rhythm. This rhythm, which is
apparently generated within the islets, is influenced by melatonin,
which induces a phase shift in insulin secretion. (iv) Observation
of the circadian expression of clock genes in the pancreas could
possibly be an indication of the generation of circadian rhythms
in the pancreatic islets themselves. (v) Melatonin influences diabetes
and associated metabolic disturbances. The diabetogens, alloxan
and streptozotocin, lead to selective destruction of beta-cells
through their accumulation in these cells, where they induce the
generation of ROS. Beta-cells are very susceptible to oxidative
stress because they possess only low-antioxidative capacity.
Results suggest that melatonin in pharmacological doses provides
protection against ROS. (vi) Finally, melatonin levels in plasma, as
well as the arylalkylamine-N-acetyltransferase (AANAT) activity, are
lower in diabetic than in nondiabetic rats and humans. In contrast,
in the pineal gland, the AANAT mRNA is increased and the insulin
receptor mRNA is decreased, which indicates a close interrelationship
between insulin and melatonin.

PMID: 18078445 [PubMed - indexed for MEDLINE]

Pharmazie. 2007 Sep;62(9):693-8.Links
Short-term melatonin treatment improved diabetic nephropathy but did not af=
hemorheological changes in diabetic rats.
Gumustekin M, Tekmen I, Guneli E, Tugyan K, Topcu A, Ergonen AT, Ozdemir MH=
,Uysal N,
Bediz CS.
Department of Pharmacology, School of Medicine, Dokuz Eylul University, Bal=
cova, Izmir,

Increased oxidative stress and hemorheological disturbances may
play very important roles in the development of microangiopathies
in diabetes mellitus. This study was designed to determine the
healing effect of melatonin on hemorheological parameters and
diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats.
Wistar male rats were divided into four groups as control, untreated-
diabetic, melatonin-treated control and melatonin-treated diabetic
rats. Diabetes was induced by injecting streptozotocin (45 mg/kg, i.p.).
Fourteen weeks after inducement of diabetes, melatonin (10 mg/kg)
was administered intraperitoneally for 5 days to the rats. Erythrocyte
deformability and aggregation were measured by laser differaction
analysis (LORCA). Diabetic nephropathy was assessed by histopathologic
evaluation and TUNEL stain in the diabetic kidney. Decreased erythrocyte
deformability and increased erythrocyte aggregation indices were
determined in the diabetic group. Melatonin treatment did not improve
these hemorheological abnormalities. However, renal injuries were
diminished in the melatonin-treated diabetic group compared to the
untreated diabetic group. Also, melatonin had an antiapoptotic effect
on the diabetic kidney. It was concluded that i.p. administration of
melatonin for 5 days improved renal injury in diabetic rats, probably
by decreasing oxidative stress, but did not affect hemorheological

J Pineal Res. 2007 Apr;42(4):350-8.
Melatonin and type 2 diabetes - a possible link?
Peschke E, Stumpf I, Bazwinsky I, Litvak L, Dralle H, M=FChlbauer E.
Institute of Anatomy and Cell Biology, Martin Luther University Halle-Witte=
nberg, Halle,

The aim of the present study was to determine the existence of
melatonin membrane receptors and to examine the mRNA
expression of nuclear orphan receptors in human pancreatic tissue,
in an effort to explain differences between type 2 diabetic and
metabolically healthy patients. Molecular and immunocytochemical
investigations established the presence of the melatonin
membrane receptors MT1 and MT2 in human pancreatic tissue and,
notably, also in the islets of Langerhans. Results of a calculation
model to determine mRNA expression ratios, as well as subjective
analysis of immunoreactions, showed elevated MT1 receptor
expression in comparison with MT2 expression. mRNA transcript
levels of melatonin receptors appeared to be significantly higher in
type 2 diabetic patients than in a control group. An upregulation of
receptor expression in type 2 diabetic patients was also observed in
immunocytochemical investigations. In addition, transcripts of the
nuclear orphan receptors RORalpha, RZRbeta, RORgamma and
RevErbalpha were detected in human pancreatic tissue and islets. In
correlation with membrane melatonin receptors, data indicate
increased mRNA expression levels of RORalpha, RZRbeta, and
RORgamma in type 2 diabetic patients. Thus, our data demonstrate
the existence of the melatonin membrane receptors MT1 and MT2
as well as mRNA expression of nuclear orphan receptors in human
pancreatic tissue, with upregulated expression levels in type 2
diabetic patients.


So, if I grasp those well enough:
It still looks like the timing was coincidental and that your ferret
developed insulin resistant diabetes as explained in Dr. William's
post included in my last post.

Sukie (not a vet)

Recommended ferret health links:


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