Type II diabetes and metabolic disorders

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).


DIABETES RESEARCH AT CDRI FOCUSES ON DEVELOPING

image01Therapeutics
image01 Knowledge-base on diabetes/dyslipidemia and metabolic syndrome through basic research.

THERAPEUTIC AIMS IN TYPE II DIABETES


image01Improving Insulin sensitivity/ glucose tolerance
image01 Reduction in serum glucose
image01 Improvement of circulating lipid profile

DRUG DESIGN AND SYNTHESIS

image01Anti-diabetic/dyslipidemic molecules by target based drug designs and synthesis:
Targets:
GLP-1 analog
DPPIV inhibitor
image01 Natural product as a source of biologically active Anti-diabetic/dyslipidemic molecules (marine/terrestrial).

SCREENING AND DRUG DEVELOPMENT
In vitro cell based screening.
image01 Glucose-uptake assays in L6 Muscle cells
image013T3L-1 –based assays on adipocyte differentiation
image01Hepatocyte based screenings on cholesterol and glucose metabolism

In vivo screening
Diabetes:
image01 Streptozotocin-induced diabetic mice
image01 Sucrose loading model
image01 db/db mice. Dyslipidemia: High fat fed Syrian hamsters.
Dyslipidemia:
image01 High fat fed Syrian hamsters

BASIC RESEARCH

image01Studies on functional regulation of carbohydrate and lipid metabolism by metabolic nuclear receptors.
image01 Proteomic analysis of 3T3L-1 cells treated with adipogenic compounds
image01 Studies on pancreatic ER stress.

SIGNIFICANT ACHIEVEMENTS


image01 CDR-134D123 (anti-hyperglycemic, Phase I): Natural product
image01 CDR134F194: IND filed
image01 Puffer fish oil: IND filed.
image01 8 lead compounds identified with anti-hyperglycemic and/oranti-dyslipidemic activities
image01 Development and optimization of proteomic approaches for proteomic profiling of lead compound treated target tissues.
image01 Development and optimization of screening systems for metabolic nuclear receptors
image01 Development of pancreatic islet cell culture for ER stress studies

Team of Coordinators
Dr. Gopal Gupta
Dr Sabyasachi Sanyal
Dr Atul Goel.
Natural Products Screening: In vivo 
Mass spectrum fingerprinting of medicinal plants 
Dr. Brajesh Kumar Dr. Anil Gaikwad 
Natural product Chemistry  Dr. S.K.Rath 
Dr Rakesh Maurya Dr D P Mishra 
 Dr J. R. Gayen 
Synthetic chemistry  Screening: In vitro 
 Dr Gitika Bhatia 
Dr Atul Goel Dr J. R. Gayen 
Dr. Atul Kumar  
Dr W Haq  
Dr T Narender Mechanism of action of lead molecules 
Dr R P Tripathi  Dr Anil Gaikwad 
 Dr Arun K Trivedi 
  Dr D P Mishra 
 Dr S Sanyal 
  Dr J. R. Gayen 
Genotoxicity and reproductive toxicity  
Dr S K Rath Dr Wahajuddin