Insulin Resistance due to Lipid-Induced Signaling Defects could be Prevented by Mahanine
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Insulin Resistance due to Lipid-Induced Signaling Defects
could be Prevented by Mahanine
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| Creator |
Biswas, Anindita
Bhattacharya, Sushmita Dasgupta, Suman Kundu, Rakesh Roy, Sib Sankar Pal, Bikas C Bhattacharya, Samir |
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| Subject |
Chemistry
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| Description |
It is well known that free fatty acids (FFAs) play
a key role in implementing insulin resistance and type 2
diabetes. Resources of chemical compounds that intervene
the derogatory effect of FFAs are indeed very limited. We
have isolated mahanine, a carbazole alkaloid, from the leaves
of Murraya koenegii that prevented palmitate-induced
inhibition of insulin-stimulated phosphorylation of IRb,
PI3K, PDK1, and Akt in L6 myotubes. This was also
reflected in the palmitate-induced inhibition of insulinstimulated
[3H] 2-DOG uptake by L6 myotubes, where
palmitate adverse effect was significantly blocked by
mahanine. Previous reports indicated that one of the major
targets of lipid-induced damage in insulin signaling pathway
resulting impairment of insulin sensitivity is insulin receptor
(IR). Here, we have observed that palmitate significantly
increased pPKCe in both cytosol and nuclear region of L6
myotubes in comparison to control. Translocation of pPKCe
to the nucleus was associated with the impairment of
HMGA1, the architectural transcription factor of IR gene and
all these were reversed by mahanine. Palmitate-induced
activation of IKK/IjB/NF-jB pathway was also attenuated by mahanine. Taken together, mahanine showed encouraging
possibility to deal with lipid induced insulin resistance. In
order to examine it further, mahanine was administered on
nutritionally induced type 2 diabetic golden hamsters; it
significantly improved hyperglycemia in all the treated animals.
Our results, therefore, suggest that mahanine acts on
two important sites of lipid induced insulin resistance (i)
impairment of IR gene expression and (ii) activation of
NF-jB pathway, thus, showing promise for its therapeutic
choice for type 2 diabetes.
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| Date |
2010
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/41/1/MOLECULAR_AND_CELLULAR_BIOCHEMIST___336_(_1%2D2);2010[109].pdf
Biswas, Anindita and Bhattacharya, Sushmita and Dasgupta, Suman and Kundu, Rakesh and Roy, Sib Sankar and Pal, Bikas C and Bhattacharya, Samir (2010) Insulin Resistance due to Lipid-Induced Signaling Defects could be Prevented by Mahanine. Molecular and cellular Biochemistry, 336 (1-2). pp. 97-107. |
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| Relation |
http://dx.doi.org/10.1007/s11010-009-0257-4
http://www.eprints.iicb.res.in/41/ |
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