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Etiopathological Study of Type 2 Diabetes Patient from India

IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata

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Title Etiopathological Study of Type 2 Diabetes Patient from India
Creator Nargis, Titli
Subject Cell Biology & Physiology
Description Type 2 Diabetes (T2DM) is an endocrine disorder characterized by high blood glucose level arising from combination of insufficient insulin secretion from pancreatic β cell and insulin resistance in peripheral tissues. High dipeptidyl peptidase 4 (DPP4) activity attenuates insulin secretion from pancreatic  cells by inactivating gut derived incretin hormones and interestingly incretin based therapy is one of the central treatment tools available for clinicians today. DPP4 is a type II transmembrane protein and it is released from the membrane through unknown mechanisms. Plasma DPP4 activity is often increased in metabolic diseases and associated with hyperglycaemia. We show that plasma DPP4 activity is significantly high in Indian T2DM patients. However, mechanism of DPP4 shedding in T2DM is largely unknown. This thesis shows an unknown cellular source and mechanism behind the enhance plasma DPP4 in T2DM patients. It uncovered that kallikrein-related peptidase 5 (KLK5) is the enzyme responsible for cleaving DPP4 from the surface of circulating CD4+ Th17 cells and shedding them into the plasma of T2DM patients. Similar cleavage and shedding activities were not seen in controls. Thus our study could be a potential approach for developing novel therapeutic strategies for hyperglycaemia. Increased DPP4 activity was shown to be independently associated with diabetes as well as obesity. As obesity is among the most important risk factors for the pathogenesis of T2DM, the relative contribution of obesity in T2DM with respect to DPP4 activity remains unclear. Using two different cohorts of non-diabetic and T2DM patients, this thesis shows that DPP4 activity is preferentially related with glycaemic control rather than obesity in T2DM patients. Hence, the research work underlying this thesis aims to examine the scope of therapeutic opportunities of DPP4 inhibitor in precision medicine.
Date 2018
Type Thesis
Format application/pdf
Identifier http://www.eprints.iicb.res.in/2782/1/Titli_Thesis_for_print_(2).pdf
Nargis, Titli (2018) Etiopathological Study of Type 2 Diabetes Patient from India. PhD thesis, University of Calcutta.
Relation http://www.eprints.iicb.res.in/2782/