Dipeptidyl Peptidase 4 Activity Is Related to Body Composition, Measures of Adiposity, and Insulin Resistance in Subjects with Excessive Adiposity and Different Degrees of Glucose Tolerance
JOURNAL OF DIABETES RESEARCH
Authors: Silva Junior, Wellington S.; Souza, Maria das Gracas C.; Nogueira Neto, Jose Firmino; Bouskela, Eliete; Kraemer-Aguiar, Luiz Guilherme
Abstract
Background. The enzyme dipeptidyl peptidase 4 (DPP4) has been recently recognized as an adipo-myokine. However, studies that associate its constitutive activity with body composition, anthropometry, and insulin resistance (IR) are very scarce and included only healthy people. Methods. First, we investigated the relationships of constitutive DPP4 activity, body composition (assessed by bioelectrical impedance analysis), and measures of adiposity and IR in fifty-two subjects of both sexes, 18-50 years, and BMI 25.0kg/m(2) who comprised three groups according to glucose tolerance. Additionally, we evaluated associations among DPP4 activity and adipokines, gut peptides, and biochemical variables at fasting and 30 and 60min after a standardized meal intake. Results. DPP4 activity was no different among the three groups. At fasting, pooled analysis showed it was positively correlated with measures of central adiposity, such as WC (P=0.011) and WHR (P=0.009), and with all measures of IR, but inversely related to indexes of general adiposity, such as fat mass percentage (P=0.014) and BAI (P=0.0003). DPP4 activity was also associated with lean mass (r=0.57, P<0.0001). After meal intake, DPP4 activity remained significantly associated with insulin, leptin, and resistin. In multiple regression analysis, BAI, WHR, percent lean mass, HOMA-IR, and leptin influenced DPP4 activity and explained approximately 26% of the variance on it. Conclusions. Constitutive DPP4 activity is positively associated with lean mass, central adiposity, and IR and negatively to general adiposity. Furthermore, it seems to be influenced by body composition and IR and could also be viewed as an adipo-myokine in subjects with excessive adiposity and different stages of glucose tolerance.
Placental proteome abnormalities in women with gestational diabetes and large-for-gestational-age newborns
BMJ OPEN DIABETES RESEARCH & CARE
Authors: Assi, Emma; D'Addio, Francesca; Mando, Chiara; Maestroni, Anna; Loretelli, Cristian; Ben Nasr, Moufida; Usuelli, Vera; Abdelsalam, Ahmed; Seelam, Andy Joe; Pastore, Ida; Magagnotti, Cinzia; Abdi, Reza; El Essawy, Basset; Folli, Franco; Corradi, Domenico; Zuccotti, Gianvincenzo; Cetin, Irene; Fiorina, Paolo
Abstract
Introduction Gestational diabetes mellitus (GDM) is the most frequent metabolic complication during pregnancy and is associated with development of short-term and long-term complications for newborns, with large-for-gestational-age (LGA) being particularly common. Interestingly, the mechanism behind altered fetal growth in GDM is only partially understood. Research design and methods A proteomic approach was used to analyze placental samples obtained from healthy pregnant women (n=5), patients with GDM (n=12) and with GDM and LGA (n=5). Effects of altered proteins on fetal development were tested in vitro in human embryonic stem cells (hESCs). Results Here, we demonstrate that the placental proteome is altered in pregnant women affected by GDM with LGA, with at least 37 proteins differentially expressed to a higher degree (p<0.05) as compared with those with GDM but without LGA. Among these proteins, 10 are involved in regulating tissue differentiation and/or fetal growth and development, with bone marrow proteoglycan (PRG2) and dipeptidyl peptidase-4 (DPP-4) being highly expressed. Both PRG2 and DPP-4 altered the transcriptome profile of stem cells differentiation markers when tested in vitro in hESCs, suggesting a potential role in the onset of fetal abnormalities. Conclusions Our findings suggest that placental dysfunction may be directly responsible for abnormal fetal growth/development during GDM. Once established on a larger population, inhibitors of the pathways involving those altered factors may be tested in conditions such as GDM and LGA, in which therapeutic approaches are still lacking.