Etiopathological Study of Type 2 Diabetes Patient from India
IR@IICB: CSIR-Indian Institute of Chemical Biology, KolkataView Archive Info
Etiopathological Study of Type 2 Diabetes
Patient from India
Cell Biology & Physiology
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
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.
Nargis, Titli (2018) Etiopathological Study of Type 2 Diabetes Patient from India. PhD thesis, University of Calcutta.