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Type
II diabetes and metabolic disorders |
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While
Type I diabetes is an autoimmune disease
which results into pancreatic beta cell
death and resultant lack of Insulin production,
Type II diabetes is scientifically most
challenging disease, which is characterized
by elevated insulin resistance and
glucose intolerance. Type II diabetes can
occur as a result of dysfunction in glucose,
lipid and energy homeostasis in any or all
of the following organs/organ systems including
liver, adipose, muscle, gastrointestinal
(GI) tract. Elevated levels of serum glucose
and free fatty acids occurring due to imbalances
in lipid and carbohydrate metabolism then
leads to endoplasmic reticular stress in
pancreatic beta cells, leading ultimately
to pancreatic beta cell death (terminal
diabetes). |
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DIABETES RESEARCH AT CDRI FOCUSES ON DEVELOPING |
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Therapeutics |
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Knowledge-base
on diabetes/dyslipidemia and metabolic
syndrome through basic research. |
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THERAPEUTIC AIMS IN TYPE II DIABETES |
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Improving Insulin
sensitivity/ glucose tolerance |
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Reduction in serum glucose |
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Improvement of circulating lipid profile |
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DRUG DESIGN AND SYNTHESIS |
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Anti-diabetic/dyslipidemic molecules
by target based drug designs and synthesis:
Targets:
GLP-1 analog
DPPIV inhibitor
PTP 1B inhibitor
SGLT2 inhibitor
Alpha-glucosidase inhibitor
Sirt1 activator |
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Natural product as a source of biologically
active
Anti-diabetic/dyslipidemic molecules
(marine/terrestrial). |
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SCREENING AND DRUG DEVELOPMENT |
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In vitro
cell based screening.
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Glucose-uptake assays in L6 Muscle
cells
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3T3L-1 –based assays on adipocyte
differentiation
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Hepatocyte based screenings on
cholesterol and glucose metabolism
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In
vivo
screening
Diabetes:
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Streptozotocin-induced diabetic mice
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Sucrose loading model
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db/db mice. Dyslipidemia: High fat
fed Syrian hamsters.
Dyslipidemia
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High fat fed Syrian hamsters |
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BASIC RESEARCH |
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Studies
on functional regulation of carbohydrate
and lipid metabolism by metabolic
nuclear receptors. |
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Proteomic
analysis of 3T3L-1 cells treated with
adipogenic compounds |
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Studies on pancreatic ER stress. |
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| SIGNIFICANT ACHIEVEMENTS |
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CDR-134D123
(anti-hyperglycemic, Phase I): Natural
product |
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CDR134F194:
IND filed |
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Puffer
fish oil:
IND filed. |
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8
lead compounds identified with anti-hyperglycemic
and/oranti-dyslipidemic
activities |
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Development and optimization of proteomic
approaches for proteomic profiling
of lead compound treated
target tissues. |
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Development and optimization of screening
systems for metabolic nuclear receptors |
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Development of pancreatic islet cell
culture for ER stress studies |
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| RECENT
PUBLICATIONS |
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Antihyperglycemic activity of phenylpropanoyl
esters of catechol glycoside and its
dimmers from Dodecadenia grandifloraManmeet
Kumar, Preeti Rawat, Neha Rahuja,
Arvind K.Srivastava, Rakesh MauryaPhytochemistry
(In press) |
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Synthesis of novel triterpenoid (Lupeol)
derivatives and their in-vivo antihyperglycemic
and antidyslipidemic activity.
K.Papi Reddy, AB Singh, A Puri, AK
Srivastava, T. Narender Bioorg.
Med. Chem. Letters (2009), 19(15):4463-6.
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Synthesis of α- amyrin derivatives
and their in vivo antihyperglycemic
activity T Narender, T Khaliq, AB
Singh, MD Joshi, P Mishra, JP Chaturvedi,
AK Srivastava, R Maurya, SC Agarwal.
European J. Med Chem. (2009), 44,
1215-1222 |
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Structure and activities of a steroidal
saponin from Chlorophytum nimonii
(Grah) Dalz.Lakshmi
V, Kumar
R, Pandey K, Joshi BS, Roy R, Madhusudanan
KP, Tiwari P, Srivastava AK.
Natural Products Research. (2009)
23(10):963-72 |
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Design and synthesis of 3, 5-diarylisoxazole
derivatives as novel class of anti-hyperglycemic
and lipid lowering agents.
Kumar A, Maurya RA, Sharma S, Ahmad
P, Singh AB, Tamrakar AK, Srivastava
AK.
Bioorg.
Med..Chem.(2009), 17(14): 5285-5292 |
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Synthetic studies in butenonyl C-glycosides:
Preparation of polyfunctional alkanonyl
glycosides and their enzyme inhibitory
activity.
Bisht SS, Fatima S, Tamrakar AK, Rahuja
N, Jaiswal N, Srivastava AK, Tripathi
RP.
Bioorg. Med. Chem. Letters (2009)
19 (10):2699-703 |
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5, 6-Diarylanthranilo-1,3-dinitriles
as a new class of antihyperglycemic
agents. Singh
FV, Parihar A, Chaurasia S, Singh
AB, Singh SP, Tamrakar AK, Srivastava
AK, Goel A Bioorg.
Med. Chem. Letters. (2009) 19(8):2158-61 |
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Synthesis of protein tyrosine phosphatase
1B inhibitors: model validation and
docking studies.
Saxena AK, Pandey G, Gupta S, Singh
AB, Srivastava AK.
Bioorg. Med. Chem. Letters. (2009)
19(8):2320-3 |
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db/+ Mice as an alternate model in
antidiabetic drug discovery research.
Tamrakar AK, Singh AB, Srivastava
AK.
Arch Med. Res., (2009) 40 (2):73-8
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Novel class of hybrid natural products
as antidiabetic agents. Raj K, Misra
N, Pachauri G, Sharma M, Tamrakar
AK, Singh AB, Srivastava AK, Phani
Kiran K, Narasimha Rao CV, Prabhu
SR. Natural Products Research (2009)
23(1):60-9 |
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Novel 2-aryl-naphtho[1,2-d]oxazole
derivatives as potential PTP-1B inhibitors
showing antihyperglycemic activities.
Kumar A, Ahmad P, Maurya RA, Singh
AB, Srivastava AK.
European J. Med. Chem. (2009) 44 (1):109-16 |
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Identification of pongamol and karanjin
as lead compounds with antihyperglycemic
activity from Pongamia pinnata
fruits. Tamrakar AK, Yadav PP, Tiwari
P, Maurya R, Srivastava AK.
J Ethnopharmacol. (2008) 118
(3):435-9 |
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Antihyperglycemic activity of
Sinularia firma and Sinularia
erecta in streptozotocin-induced
diabetic rats. Akhilesh K. Tamrakar,
Priti Tiwari, Rehan Ahmad, Rajesh
Kumar, Vijai Lakshmi, Mahendra Nath
Srivastava, Arvind K. Srivastava
Med. Chem. Res., (2008) 17:62-73 |
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.Synthesis of 3,5-disubsituted isoxazolines
as protein tyrosine phosphatase 1B
inhibitors.Rakesh Maurya, Prasoon
Gupta, Ghufran Ahmad, Dinesh Kumar
Yadav, Kailash Chand, Amar Bahadur
Singh, Akhilesh K. Tamrakar, Arvind
K. Srivastava
Med. Chem. Res. (2008) 17:123-136 |
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Synthesis and antihyperglycemic activity
of novel N-acyl-2-arylethylamines
and N-acyl-3-coumarylamines. Dwivedi
AP, Kumar S, Varshney V, Singh AB,
Srivastava AK, Sahu DP. Bioorg. Med.
Chem. Letters. (2008) 18(7):2301-5
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TEAM OF THE DIABETES, DYLIPIDEMIA AND METABOLIC DISORDER |
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