Increased urocortin 3 levels are associated with the risk of having type 2 diabetes mellitus

Abstract

Background: Urocortin 3 (UCN3) is a peptide hormone playing a pivotal role in glucose and lipid metabolisms. However, its clinical implications remain unclear. Our aims were to investigate the altered levels of UCN3 in newly diagnosed type 2 diabetes mellitus (nT2DM) patients in comparison to subjects with normal glucose tolerance (NGT) and to determine the presence of any possible link between UCN3 levels and metabolic parameters.Methods: Eighty nT2DM and 80 age-, body mass index (BMI)-, and gendermatched NGT subjects were enrolled into this case-control study. The circulating UCN3 levels were measured using the enzyme-linked immunoabsorbent assay (ELISA). Metabolic parameters of enrolled subjects were also determined. A standard 75-g 2-hour oral glucose tolerance test was used for diagnosis of type 2 diabetes mellitus (T2DM). Results: UCN3 levels were higher in subjects with nT2DM than in controls (115.64 ± 39.26 vs 86.16 ± 22.81 pg/mL, P < .001). UCN3 levels were increased in subjects with metabolic syndrome compared to subjects without metabolic syndrome in both nT2DM and NGT groups. UCN3 levels showed a positive correlation with BMI in both groups. Moreover, UCN3 levels were positively and independently associated with insulin, fasting blood glucose, insulin resistance, 2-hour plasma glucose, glycosylated hemoglobin, and triglycerides, whereas UCN3 levels were negatively and independently associated with high-density lipoprotein cholesterol. According to logistic regression analysis, increased risk of T2DM and metabolic syndrome were parallel with the highest elevated levels of UCN3.Conclusions: Increased levels of UCN3 are associated with unfavorable metabolic profiles in T2DM, indicating a potential role of UCN3 in glucose and lipid metabolisms in T2DM. Highlights• Urocortin 3 (UCN3) may play a crucial role in glucose and lipid metabolisms.

Assessment of clinical data on urocortins and their therapeutic potential in cardiovascular diseases: A systematic review and meta‐analysis

“… 48 Another study reported elevated Ucn3 levels in subjects with newly diagnosed type 2 diabetes mellitus as compared with controls. 49 …”

“…In case of Ucn3, higher hormone levels were demonstrated for a number of pathological conditions, such as metabolic syndrome, diabetes mellitus type 2, polycystic ovary syndrome (PCOS), or obesity, but not for HF or for other cardiovascular diseases. 48,49,53 Because all Ucn levels were determined by ELISA techniques, gross differences in measurement could not contribute to the substantial heterogeneity of our results. Other factors, such as BMI, age, and sex, may have contributed to the heterogeneity of these findings.…”

“…21,39,42,43 Interestingly, we did not find remarkable differences among Ucn types and in their association with specific cardiovascular diseases. Moreover, blood Ucn levels appear to increase in a number of other general systemic challenges, including metabolic syndrome, 49 PCOS, 53,54 or type 2 diabetes mellitus. 48,49 Thus, increases in Ucn levels may not even be specific for cardiovascular disorders or HF.…”

“…In case of Ucn3, higher hormone levels were demonstrated for a number of pathological conditions, such as metabolic syndrome, diabetes mellitus type 2, polycystic ovary syndrome (PCOS), or obesity, but not for HF or for other cardiovascular diseases. 48 , 49 , 53 …”

Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in diabetic nephropathy

“…SERPINA3 [41], IKZF1 [42], BTK (Bruton tyrosine kinase) [43], C1QA [44], CD1C [45] and CCL13 [46] have a key role in lupus nephritis, but these genes might be liable for advancement of DN. TNFSF14 [47], ITGAL (integrin subunit alpha L) [48], PLAC8 [49], ADRA2A [50], CCL21 [51], ALOX5 [52], CNR2 [53], COL1A1 [54], WNT7A [55], SLAMF1 [56], CD3D [57], LTF (lactotransferrin) [58], MIR27B [59], PDK4 [60], UCN3 [61], PCK1 [62], CEL (carboxyl ester lipase) [63], TRPM6 [64], MTTP (microsomal triglyceride transfer protein) [65], CYP2C8 [66] and CYP3A4 [67] have important role in the progression of type 2 diabetes via in ammation , but these genes might be crucial role in DN progression. Zhang et al [68], Ellenbroek et al [69], Guo et al [70] and Tillmanns et al [71] have shown that MZB1, LAIR1, MIR142 and FAP ( broblast activation protein alpha) modulating mitochondrial function and alleviating in ammation in myocardial infarction, but these genes might be involved in progression of DN.…”