Renuka, T R; Ani Das, V; Paulose,C S(Department of Biotechnology, March 2, 2004)
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Abstract:
Muscarinic M1 and M3 receptor changes in the brain stem during pancreatic regeneration were investigated.
Brain stem acetylcholine esterase activity decreased at the time of regeneration . Sympathetic activity also
decreased as indicated by the norepinephrine (NE) and epinephrine (EPI) content of adrenals and also in the
plasma. Muscarinic Ml and M3 receptors showed reciprocal changes in the brain stem during regeneration.
Muscairnic M1 receptor number decreased at time of regeneration without any change in the affinity. High affinity
M3 receptors showed an increase in the number. The affinity did not show any change . The number of low affinity
receptors decreased with decreased Kd at 72 hours after partial pancreatectomy. The Kd reversed to control value
with a reversal of the number of receptors to near control value . Gene expression studies also showed a similar
change in the mRNA level of Ml and M3 receptors . These alterations in the muscarinic receptors regulate
sympathetic activity and maintain glucose level during pancreatic regeneration. Central muscarinic M1 and M3
receptor subtypes functional balance is suggested to regulate sympathetic and parasympathetic activity, which in
turn control the islet cell proliferation and glucose homeostasis.
Ani Das, V; Finla, Chathu; Paulose,C S(Department of Bio Technology, April 20, 2006)
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Abstract:
Sympathetic stimulation inhibits insulin secretion. a2-Adrenergic receptor is known to have a regulatory role in the sympathetic function. We
investigated the changes in the a2-adrenergic receptors in the brain stein and pancreatic islets using [3H]Yohimbine during pancreatic regeneration
in weanling rats. Brain stem and pancreatic islets of experimental rats showed a significant decrease (p<0.001) in norepinephrine (NE) content at
72 h after partial pancreatectomy. The epinephrine (EPI) content showed a significant decrease (p<0.001) in pancreatic islets while it was not
detected in brain stem at 72 h after partial pancreatectomy. Scatchard analysis of [3H]Yohimbine showed a significant decrease
(p<0.05) and Kd at 72 h after partial pancreatectomy in the brain stem. In the pancreatic islets, Scatchard analysis of [3H]Yohimbine showed a signiinfiBca'nnatx
decrease (p<0.001) in B,nax and Kd (p<0.05) at 72 h after partial pancreatectomy. The binding parameters reversed to near sham by 7 days after
pancreatectomy both in brain stein and pancreatic islets. This shows that pancreatic insulin secretion is influenced by central nervous system inputs
from the brain stem. In vitro studies with yohimbine showed that the a2-adrenergic receptors are inhibitory to islet DNA synthesis and insulin
secretion. Thus our results suggest that decreased a2-adrenergic receptors during pancreatic regeneration functionally regulate insulin secretion
and pancreatic 13-cell proliferation in weanling rats.
Balarama Kaimal,S; Gireesh,G; Paulose,C S(Department of Biotechnology, January 4, 2007)
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Abstract:
Gamma amino outyric acid is a major
inhibitory neurotrarsr titter in the central nervous
system. In the preset study sv, Have investigate(' the
alteration of GABA receptor, In t he hrain stem of rats
during pancreatic regeneration. Three groups of rats
were used for the study: sham operated, 72 It and
7 days partially pancreatectonnsea. GABA was (juan-
(ified by [H]GABA receptor iispiacement method.
GABA receptor kin: 10, pat at i et•ers were studied by
using the binding of F'.](iAhA as ligand to the Triton
X-100 treated me,i1,;-:mes a1,J displacement with
unlabelled GABA. GhRA,v receptor activity was
studied by using the [` -1 h3cuculline and displacement
with unlabellecV euculline. ;.\13A content significantly
decreased (1' < (1.(101 ) it, 0-e brain stern during
the regeneration of pancreas. 'I hl, high affinity (IAI3A
receptor binding sho?:ed it sigii'f cant decrease in 131„.,\
(P < 11.01) and K,I 1).05) n 72 h and 7 days after
partial pancreatee 'timv. ";:flhicuculline hin(Iing
showed it signih eat, 'le ( r(, :,e in /Jn1,s and K,I
(P < 0.001) in 72 h pa^.rcreaw,, mised rats when compared
with sham wt--tt' as P,n and K,I reversed to
near sham after 7 da,s of pancreatectomv. The results
sugge,) that GAB A throur,r; ('GABA receptors in
brain Atcem has a regulatory uie during active regeneration
of pancreas which will have inunense clinical
significance in the treatment of cliahetcs.