Division of Endocrinology and Metabolism
 

Objectives of the division

  1. To conduct basic and applied research on endocrine disorders of relevance to the country such as obesity, Insulin resistance and the associated adult onset chronic diseases like type 2 diabetes, hypertension, cardiovascular diseases, cancer etc including the role of maternal nutritional status in foetal programming for these diseases.

  2. To decipher the endocrine, neuropeptide, neurotransmitter, neurotrphin signalling mechanisms and expression and / or activity of relevant genes especially in the hypothalamus / brain cortex, underlying hyperphagy, obesity and accelerated ageing in the Wistar NIN obese rat model. Also assess their modulation by calorie restriction with / without the associated micronutrient deficiencies

  3. To generate a database on the antioxidant activity of common Indian plant foods and the contribution to it of their phenolic content including the effect of common processing and their bioavailability.

  4. To determine the proteasome inhibitory activity of the phenolic rich plant foods and assess their efficacy in cancer therapy.

  5. To evaluate the role of the ubiquitin proteasome pathway in vitamin D deficiency induced muscle atrophy and hypoinsulinemia.

  6. To develop human resources capable of carrying out endocrinological techniques of relevance to the country.


Research achievements in the recent past

  1. Unequivocal demonstration using animal models, of the importance of maternal micronutrient status per se (deficiencies of vitamins, minerals, Mg, Cr, Zn, Mn, folic acid and vitamin B12) in modulating / programming variably, the body composition of the offspring in a way that they may be at greater risk of developing the adult onset degenerative diseases in their later life. Demonstration of the probable importance of oxidative and glucocorticoid stress in this process and the finding that maternal vitamin restriction but not mineral restriction induced phenotypic (but not associated biochemical and physiological) changes in the offspring may be prevented / reversed by appropriate rehabilitation. Demonstration of probable associated molecular mechanisms (differentially expressed genes) in the development of adiposity and IR in micronutrient restriction induced rat model.   

  2. Demonstration that impaired hypothalamic insulin signalling and / or altered neuropeptide, neurotransmitter and endocrine mechanism(s) could underlie the hyperphagy and obesity in the WNIN /Ob rat model. Preliminary evidence suggests that altered IGF1 and / or BDNF signalling may underlie accelerated ageing in these obese mutant rats of NIN.

  3. Generation of a database of the total phenolic content and antioxidant activity of about 110 common Indian plant foods belonging to different classes ( eg. cereals, millets, pulses, legumes, vegetables etc) along with the demonstration that phenolic compounds may be important contributors to the antioxidant activity of many but not all of them. Limited data preliminary showing that different types of domestic processing may affect these parameters variably and development of a few antioxidant activity rich recipes based on the data generated.

  4. As a participant in the DLHS II survey, the division analyzed around 1.8 lakh blood samples (dried blood spots on filter paper circles) from mothers and children from 300 districts of the country for their haemoglobin content. 

  5. Preliminary observations show that certain plant foods rich in polyphenolic compounds possess proteasome inhibitory activity and could therefore be of importance in cancer chemotherapy.  

  6. Preliminary findings suggest that muscle atrophy seen in experimental vitamin D deficiency in albino rats may be associated / preceded by increased proteolytic activity of the 26S proteasome.

  7. We have conducted --- annual certificate courses during the last decade and trained --- candidates in the Endocrinological techniques and their application to research and diagnostic / prognostic purposes


Present Research Activities

  1. Molecular mechanism(s) underlying the maternal micronutrient restriction induced changes in the rat offspring,  including changes in the expression of relevant genes ( by candidate gene approach ,DNA microarrays and pathway based gene expression by RT – PCR arrays) and their modulation by rehabilitation vis a vis the phenotypic changes.

  2. Assess whether impairment / alteration in the neuro musculo skeletal development underly / associated with maternal micronutrient (Mg) restricition induced changes in the body composition of the rat offspring and their prevention / reversibility by rehabilitation.

  3. Determine whether alterations in expression / signalling / activity of IGF1 and BDNF in the brain underlie accelerated ageing in the WNIN / Ob mutant rats. If yes, assess their modulation by calories restriction with / without concurrent micronutrient restriction vis a vis the accelerated ageing seen in them. 

  4. Evaluate the anti hyperglycaemic potential of simple binary, ternary and quaternary complexes of  Chromium with a few amino acids present in the yeast Glucose tolerance factor. If found to have the effect, determine the possible mechanism(s) of their effect and evaluate their usefulness as adjuncts in the treatment of Diabetes.

  5. Determination of Hb content in about 7.5 lakh blood samples ( dried blood spots on filter paper circles) of subjects of different physiological groups and ages as a part of the DLHS IV survey and the survey by the Registrar general of India.

  6. Screen / identify the plant foods rich in phenolics for their proteasome inhibitory activity and assess their effect / efficacy in inhibiting cancer cell proliferation. Isolate, purify and characterize the active principle from the food source found to have the highest proteasome inhibitory potential and evaluate its efficacy in cancer using cell culture and animal models.

  7. Determine the role of the ubiquitin proteasome pathway in vitamin D deficiency induced muscle atrophy in a rat model vis a vis the actual mechanism of the effect. Assess the modulation of the proteolytic pathway in the vitamin D deficient rat by vitamin D and / or high calcium supplementation and study the reversibility of the muscle wasting.

  8. Certificate course on Endocrinological techniques and their application to continue to train personnel.

Thrust areas for future

  1. Relevance of epigenetic mechanism(s) (DNA methylation, histone modifications and micro RNAs) and their modulation in the maternal undernutrition (of micronutrients) induced phenotypic/ biochemical / physiological changes in the offspring and their prevention / reversibility by nutrient rehabilitation.

  2. Development of a mouse model for developmental programming for the body composition and associated disorders in the offspring considering that the mouse is genetically closer to humans than the albino rat.

  3. Assess the role of modulated tissue vascularisation, differentiation / development, mitochondrial function, cell senescence and tissue insulin resistance in the foetal programming for adiposity and associated diseases in the offspring

  4. Role of Ubiquitin- proteasome pathway in vitamin D deficiency induced muscle atrophy.

  5. Screening polyphenol rich plant foods for their proteasome inhibitory activity. Isolation, purification and characterization of the active component(s) from the food source. Determine the apoptosis inducing potential of the component(s) and its role as an anti-cancer agent.  

  6. Etio-pathogenesis of pre and post menopausal osteoporosis: A molecular approach.

  7. Diet induced obesity : Meatbolome aterations / signatures

  8. In-silico approach to characterize CpG and CGI methylation of obese genes

    
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