Pharmaspire


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Pages: 202-206

Date of Publication: 30-Nov--0001

Pathological role of dipeptidyl peptidase (DPP) -4 in liver and ameliorative effects of dpp-4 inhibitors

Author: Divya Sharma, Gaaminepreet Singh

Category: Pharmaceutics

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Abstract:

Dipeptidyl peptidase 4 (DPP4) is the target of the gliptins, a recent class of oral ant diabetics. DPP4 (also called cluster of differentiation 26) was previously characterized in immune cells but also has important metabolic functions which are not yet fully understood. Thus, we investigated the function of DPP4 in human white preadipocytes and adipocytes. We found that both cell types express DPP4 in high amounts; DPP4 release markedly increased during differentiation. In preadipocytes, lentiviral DPP4 knockdown caused significant changes in gene expression as determined by wholegenome DNA-array analysis. Metabolic genes were increased, forexample, PDK4 18- fold and PPAR__ampersandsigngamma;C1__ampersandsignalpha; (=PGC1__ampersandsignalpha;) 6-fold, and proliferation elated genes were decreased (e.g. FGF7 5-fold). These effects, contributing to differentiation, were not inhibited by the PPAR__ampersandsigngamma; antagonist T0070907. Vice versa, the PPAR__ampersandsigngamma; agonist pioglitazone induced a different set of genes (mainly FABP4). DPP4 knockdown also affected growth factor signaling and, accordingly, retarded preadipocyte proliferation. In particular, basal and insulin-induced ERK activation (but not Akt activation) was markedly diminished (by around 60%). This indicates that DPP4 knockdown contributes to adipocyte maturation by mimicking growth factor withdrawal, an early step in fat cell differentiation. In mature adipocytes, DPP4 becomes liberated so that adipose tissue may constitute a relevant source of circulating DPP4.

Keywords: Dipeptidyl peptidase 4, adipocytes, pre-adipocytes, hepatocyte, adipokine

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