Decreased muscarinic M1 receptor gene expression in the cerebral cortex of streptozotocin-induced diabetic rats and Aegle marmelose leaf extract's therapeutic function.
OBJECTIVE
In the present study we have investigated the changes in the total muscarinic and muscarinic M1 receptor ([(3)H]QNB) binding and gene expression in the cerebral cortex of streptozotocin (STZ) induced diabetic, insulin and aqueous extract of Aegle marmelose leaf treated diabetic rats.


METHODS
Diabetes was induced in rats by intrafemoral injection of streptozotocin. Aegle marmelose leaves was given orally to one group of rats at a dosage of 1g/kg body weight per day for fourteen days. Blood glucose and plasma insulin level were measured. Muscarinic and Muscarinic M1 receptor binding studies were done in the cerebral cortex of experimental rats. Muscarinic M1 receptor gene expression was studied using real-time PCR.


RESULTS
Scatchard analysis for total muscarinic receptors in cerebral cortex showed that the B(max) was decreased significantly (p<0.001) in diabetic rats with a significant decrease (p<0.01) in the K(d) when compared to control group. Binding analysis of Muscarinic M1 receptors showed that B(max) was decreased significantly (p<0.001) in diabetic group when compared to control group. The K(d) also decreased significantly (p<0.01) when compared to control group. The binding parameters were reversed to near control by the treatment of diabetic rats with Aegle marmelose. Real-Time PCR analysis also showed a similar change in the mRNA levels of muscarinic M1 receptors.


CONCLUSIONS
The results showed that there is decrease in total muscarinic and muscarinic M1 receptors during diabetes which is up regulated by insulin and Aegle marmelose leaf extract treatment. This has clinical significance in therapeutic management of diabetes.
Gireesh
Gangadharan
G
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Cochin University of Science and Technology, Cochin 682 022, Kerala, India.
Reas
S Khan
SK
Jobin
Mathew
M
Paulose
Cheramadathikudiyil Skaria
CS
D045471:Aegle / Q000737:chemistry*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D011863:Radioimmunoassay; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1 / Q000235:genetics*; D013311:Streptozocin
D001786:Blood Glucose; D007328:Insulin; D010936:Plant Extracts; D043643:Receptor, Muscarinic M1; D013311:Streptozocin