Tessy,Maliekal T; Sudha, B; Paulose,C S(Department of Biotechnology, February 14, 1997)
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Abstract:
The role of thyroid hormones in DNA synthesis and in the activity of Thymidille
kinase (TK), a key regulatory enzyme of DNA synthesis was studied in proliferating
hepatocytes in vivo. Liver regeneration after partial hepatectomy was used as a
model for controlled cell division in rats having different thyroid status - euthyroid,
hypothyroid and 3,3',5'-triiodo-L-thyronine (T))-heated hypothyroid. Partial
hepatectomy caused a significant elevation of DNA synthesis (p<0.01) in all the three
groups compared to their sham-operated counterparts. Hypothyroid liepatectomised
animals showed significantly lower (p<0.01) level of DNA synthesis than euthyroid
hepatectomised animals. A single subcutaneous close of 1'3 to hypothyroid shamoperated
animals resulted in a significant increase (p<0.01) of DNA synthesis in the
intact liver. 17tis was comparable to the level of DNA synthesis occurring in
regenerating liver of euthyroid animals. In hypothyroid hepatectomised animals, "1'3
showed an additive effect on l)NA synthesis and this group exhibited maximum level
of DNA synthesis (p<0.0I ). Studies of the kinetic parameters of TK show that the
Michelis-Menten constant, (K111) of TK for thymidine was altered by the thyroid
status. K11 increased significantly (p<0.01) in untreated hypothyroid animals when
compared to the euthyroid rats. '13 treatment of hypothyroid animals reversed this
effect and this group showed the lowest value for K111 (p<0.01). Thus our results
indicate that thyroid hormones can influence DNA synthesis during liver regeneration
and they may regulate the activity of enzymes such as 17rymidine kinase which are
important for DNA synthesis and hence cell division.
Renuka, T R; Paulose,C S(DEPARTMENT OF BIOTECHNOLOGY, June , 2003)
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Abstract:
The present work is an attempt to understand the role of acetylcholine
muscarinic M1 and M3 receptors during pancreatic regeneration and insulin
secretion. The work focuses on the changes in the muscarinic M1 and M3 receptors
in brain and pancreas during pancreatic regeneration. The effect of these receptor
subtypes on insulin secretion and pancreatic P-cell proliferation were studied in vitro
using rat primary pancreatic islet culture. Muscarinic Ml and M3 receptor kinetics
and gene expression studies during pancreatic regeneration and insulin secretion will
help to elucidate the role of acetylcholine functional regulation of pancreatic u-cell
proliferation and insulin secretion.The cholinergic system through muscarinic M1
and M3 receptors play an important role in the regulation of pancreatic (3-cell
proliferation and insulin secretion . Cholinergic activity as indicated by acetylcholine
esterase, a marker for cholinergic system, decreased in the brain regions -
hypothalamus, brain stem, corpus striatum, cerebral cortex and cerebellum during
pancreatic regeneration. Pancreatic muscarinic M1 and M3 receptor activity increased during proliferation indicating that both receptors are stimulatory to (3-cell division. Acetylcholine dose dependently increase EGF induced DNA synthesis in pancreatic islets in vitro, which is inhibited by muscarinic antagonist atropine confirming the role of muscarinic receptors. Muscarinic M1 and M3 receptor antagonists also block acetycholine induced DNA synthesis suggesting the importance of these receptors in regeneration. Acetylcholine also stimulated glucose induced insulin secretion in vitro which is inhibited by muscarinic M1 and M3 receptor antagonists. The muscarinic receptors activity and their functional balance in the brain and pancreas exert a profound influence in the insulin secretion and also regeneration of pancreas