Jackson,James; Paulose,C S(Department of Biotechnology, May 1, 2000)
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Abstract:
5-HT2A receptor binding parameters were studied in the cerebral cortex and brain stem of
control, diabetic, insulin, insulin + tryptophan and tr3yptophan treated streptozotocin diabetic
rats. Scatchard analysis using selective antagonist, [-H](±)2,3-dimethoxyphenyl-l-[2-(4-piperidine)-
methanol] ([3H]MDL100907) in cerebral cortex of diabetic rats showed a significant
decrease in dissociation constant (Kd) without any change in maximal binding (Bm). Competition
binding studies in cerebral cortex using ketanserin against [3H]MDL100907 showed
the appearance of an additional site in the low affinity region during diabetes. In the brain
stem, Scatchard analysis showed a significant increase in Bmax and Kd. Displacement studies
showed a shift in the receptor affinity towards a low affinity state. All these altered parameters
in diabetes were reversed to control level by insulin, insulin + tryptophan and tryptophan
treatments. Tryptophan treatment is suggested to reverse the altered 5-HT2Abinding and
blood glucose level to control status by increasing the brain 5-HT content.
Biju,M P; Paulose,C S(Department of Biotechnology, September 27, 1997)
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Abstract:
Kinetic parameters of brain glutamate dehydrogenase (GDH) were compared in the brain
stem, cerebellum and cerebral cortex of three weeks and one year old streptozotocin (STZ)
induced four day diabetic rats with respective controls. A single intrafemoral dose of STZ
(60mg/Kg body weight) was administered to induce diabetes in both age groups. After four days
the blood glucose levels showed a significant increase in the diabetic animals of both age groups
compared with the respective controls. The increase in blood glucose was significant in one year
old compared to the three weeks old diabetic rats. The Vmm of the enzyme was decreased in all
the brain regions studied, of the three weeks old diabetic rats without any significant change in
the Km. In the adult the Vmax of GDH was increased in cerebellum and brain stem but was
unchanged in the cerebral cortex. The K. was unchanged in cerebellum and cerebral cortex but
was increased in the brain stem. These results suggest there may be an important regulatory role
of the glutamate pathway in brain neural network disturbances and neuronal degeneration in
diabetes as a function of age.
Eswar Shankar,P N; Anu, Joseph; Paulose,C S(Department of Biotechnology, May 17, 2006)
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Abstract:
In the present study dopamine was measured in the hypothalamus, brainstem, pancreatic islets and plasma, using HPLC. Dopamine D2 receptor
changes in the hypothalamus, brainstem and pancreatic islets were studied using [3H] YM-09151-2 in streptozotocin-induced diabetic and insulintreated
diabetic rats. There was a significant decrease in dopatnine content in the hypothalamus (P<0.001), brainstem (P<0.001), pancreatic islets
(P<0.001) and plasma (P<0.00I) in diabetic rats when compared to control. Scatchard analysis of [3H] YM-09151-2 in the hypothalamus of
diabetic rats showed a significant decrease in Bax (P<0.001) and Kd, showing an increased affinity of D2 receptors when compared to control.
Insulin treatment did not completely reverse the changes that occurred during diabetes. There was a significant decrease in B,nax (P<0.01) with
decreased affinity in the brainstem of diabetic rats. The islet membrane preparation of diabetic rats showed a significant decrease (P<0.001) in the
binding of [3H] YM-09 151-2 with decreased Kd (P<0.001) compared to control. The increase in affinity of D2 receptors in hypothalamus and
pancreatic islets and the decreased affinity in brainstem were confirmed by competition analysis. Thus our results suggest that the decreased
dopamine D, receptor function in the hypothalamus, brainstem and pancreas affects insulin secretion in diabetic rats, which has immense clinical
relevance to the management of diabetes.
Eswar Shankar,P N; Santhosh,K T; Paulose,C S(Department of Biotechnology, March , 2006)
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Abstract:
The stimulatory effect of dopamine through dopamine 1)2
receptor on glucose - induced insulin secretion was studied in the
pancreatic islets in nitro. I)oparnilie signifieanlly stimula(ed insulin
secretion at a concentration of 10 a N1 in the presence of
high,glucose ( 20 nii1 ). ' fhe higher concentrations of dopamine
(111 -1() 4) inhibited glucose- induced insulin secretion in the
presence of both 4 mM1 and 20 m M glucose. Stimulatory and
inhibitory effect of dopamine on glucose - induced insulin secretion
was reverted by the addition of dopamine 1)2 receptor antagonists
such as butaclamol and sulpiride . Norepinephrine (NE) at 111 4 11
concentration inhibited the dopamine uptake as well as its
stimulatory effect at 11) - 8 IN1 concentration on glucose induced
insulin secretion. Our results suggest that dopamine exerts a
differential effect on glucose -induced insulin secretion through
dopamine D2 receptor and it is essential for the regulation of
glucose-induced insulin secretion by pancreatic islets.