Significance of circulatory DPP4 activity in metabolic diseases

Abstract

Dipeptidyl peptidase 4 (DPP4), also known as CD26 is a type II transmembrane protein that is released from the cell membrane in a nonclassical secretory mechanism. This exopeptidase selectively degrades varieties of substrates including incretin hormones, growth factors, and cytokines. A significant detectable amount of DPP4 activity can be measured in plasma as well as in different tissues such as intestinal epithelium, vascular endothelium, lymphocytes, monocytes, kidney, liver, adipose, lung, thymus, spleen, prostate, etc. Enzymatically active circulatory DPP4 is shed from the plasma membrane via proteolytic cleavage, a process responsible for the enhanced plasma DPP4 levels and activity. Elevated circulatory DPP4 activity as well as levels has been found in wide spectrum of metabolic diseases including diabetes, obesity, cardiovascular diseases, and nonalcoholic fatty liver diseases. Moreover, recent preclinical studies have further expanded the repertoire for the usage of DPP4 inhibitors in the treatment of other metabolic diseases and in their consequent complications. In the present review we highlight the reason behind the elevated circulatory DPP4 levels in metabolic diseases with a focus on the tissue of origin. We also underscore the discrepancy of protein levels with enzyme activity of circulatory DPP4 in metabolic diseases. © 2018 IUBMB Life, 70(2):112-119, 2018.

DPP4 Polymorphisms Are Associated With Hypoalphalipoproteine mia and DPP4 Serum Levels. A Case-control Study of the GEA Cohort.

“…It has been reported that in smooth muscle cells and adipocytes, hypoxia increased DPP4 shedding by matrix metalloproteases [59]. The constitutive shedding mechanism of DPP4 is varied with cell speci city as well as cells and tissues circumstances and occurs due to a complex interplay between different proteases in cell type-speci c manner [60]. Our results showed that non-HA subjects have signi cantly higher DPP4 concentrations.…”

Identification of Susceptibility Genes to Allergic Rhinitis by Gene Expression Data Sets

“…SH2D1B, is predominantly expressed in the innate immune cells, such as the macrophages and dendritic cells, whose upregulation has been speculated to help modulate the kinetics of a series of vital proinflammatory cytokine and chemokine responses . DPP4, also referred to CD26, is a type II transmembrane protein that exhibits enhanced levels in an extensive range of metabolic diseases involving diabetes, cardiovascular diseases, and obesity, as well as nonalcoholic fatty liver diseases . Notably, the silencing DPP4 in hepatocytes has been reported to repress the inflammation seen in visceral adipose tissues as well as diminishing the insulin resistance associated with obesity .…”

“…25 DPP4, also referred to CD26, is a type II transmembrane protein that exhibits enhanced levels in an extensive range of metabolic diseases involving diabetes, cardiovascular diseases, and obesity, as well as nonalcoholic fatty liver diseases. 26 Notably, the silencing DPP4 in hepatocytes has been reported to repress the inflammation seen in visceral adipose tissues as well as diminishing the insulin resistance associated with obesity. 27 Evidence has demonstrated the involvement of DPP4 in certain immunological processes, which play a significant role in the lung's allergic responses.…”

Dysregulated activities of proline-specific enzymes in septic shock patients (sepsis-2)

“…FAP enzyme activity is known to be increased in certain liver diseases and decreased in certain malignancies, but remains unchanged in rheumatoid arthritis or scleroderma [43]. Unfortunately, the exact sources or mechanisms by which these enzymes are released into the bloodstream are not fully understood [44,45]. It is plausible that these secretion or shedding mechanisms are disturbed.…”