Liver injury and dysregulated glucose homoeostasis are common manifestations during sepsis. Although plenty of studies reported insulin could protect against multiple organ injuries caused by critical infections among patients, little was known about the precise mechanism. We investigated whether liver inflammatory pathway and central neuropeptides were involved in the process. In sepsis rats, hepatic IKK/NF‐κB pathway and STAT3 were strongly activated, along with reduced body weight, blood glucose and suppressed hepatic gluconeogenesis (GNG). Peripheral insulin administration efficiently attenuated liver dysfunction and glucose metabolic disorders by suppressing hypothalamic anorexigenic neuropeptide proopiomelanocortin (POMC) expression, hepatic NF‐κB pathway and STAT3 phosphorylation. Furthermore, knockdown of hypothalamic POMC significantly diminished protective effect of insulin on hepatic GNG and insulin‐induced STAT3 inactivation, but not inflammation or IKK/NF‐κB pathway. These results suggest that hepatic IKK/NF‐κB pathway mediates the anti‐inflammatory effect of insulin in septic rats, and peripheral insulin treatment may improve hepatic GNG by inhibiting STAT3 phosphorylation dependent on hypothalamic POMC expression.
Background. Tenascin-C (TNC), an extracellular matrix glycoprotein, is elevated in inflammatory and cardiovascular pathologies, whereas alarin, a novel orexigenic peptide, participates in insulin resistance and glycometabolism. The roles of these molecules in individuals with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), clinical conditions associating with metabolic disorders, and chronic inflammation, remain controversial. Our study aimed at determining the potential role of TNC and alarin in CVD adult patients with T2DM. Methods. This was a cross-sectional study. Basic and clinical information for 250 patients with T2DM were analyzed. Based on their cardiovascular disease status, participants were assigned into the CVD and non-CVD groups. Serum TNC and alarin levels were assessed by enzyme-linked immunosorbent assay (ELISA). Results. Serum TNC and alarin concentrations in the CVD group were significantly higher than those of the non-CVD group. Moreover, serum TNC levels were positively correlated with age, waist circumference, and waist-hip ratio; however, they were negatively correlated with TC, LDL-C, and eGFR levels. Alarin levels were positively correlated with BMI, waist circumference, and hip circumference. In logistic regression models, TNC and alarin were also established to be independent determinants for CVD in T2DM patients and their increases were associated with CVD severity. Receiver operating characteristic (ROC) curve analysis showed that the area under curve (AUC) values for TNC and alarin were 0.68 and 0.67, respectively. TNC and alarin were good predictors of CVD occurrence. When the cutoff value for TNC was 134.05 pg/mL, its sensitivity was 69.47% while its specificity was 61.29%. When the cutoff value for alarin was 142.69 pg/mL, sensitivity and specificity were 38.95% and 90.97%, respectively. Conclusion. Elevated TNC and alarin levels are independently associated with the occurrence and severity of CVD in T2DM individuals. Therefore, these two biomarkers are potential diagnostic and prognostic indicators for CVD in diabetics.
Background: The prevalence of peripheral artery disease (PAD) is obviously increased in diabetic patients. Existing evidences show that cysteine-rich angiogenic inducer 61 (Cyr61), a 40 kD secreted protein, plays important roles in regulating cellular physiological processes. Recent studies have demonstrated a significant correlation between serum Cyr61 levels and atherosclerosis. However, the relationship between Cyr61 levels and PAD in type 2 diabetic patients remains obscure.Methods:. A total of 306 subjects with type 2 diabetes were recruited. The extent of PAD was determined by using the Fontaine classification, which defines four stages. We analyzed Cyr61 serum levels by ELISA in patients with and without PAD at Fontaine’s stage II, III, or IV. Logistic regression models were used to examine the independent association of Cyr61 with PAD.Results: Out of the 306 patients enrolled in this study, 150 patients were free from PAD, while 156 had clinically significant PAD. In PAD patients, the prevalences of Fontaine classification stage II, III and IV were 48.7%, 32.1%, and 19.2%, respectively. Patients with more advanced PAD had significantly higher Cyr61 (P for trend <0.001). The prevalence of PAD on the basis of severity increased with ascending Cyr61 quartiles (all P for trend <0.001), and the severity of PAD was positively correlated with Cyr61 quartiles (r=0.227, P=0.006). The association of Cyr61 levels with PAD remained after adjusting for major risk factors in a logistic regression analysis.Conclusions: Our results demonstrated that Cyr61 was significantly increased in type 2 diabetic patients with PAD and that Cyr61 levels were positively associated with disease severity. It could be a promising biomarker and further studies are needed to assess its clinical utility.
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