thymosin and Hyperglycemia

High-risk pregnancies, such as pregnancies with gestational diabetes mellitus (GDM), are becoming more common and as such, have become important public health issues worldwide. GDM increases the risks of macrosomia, premature infants, and preeclampsia. Although placental dysfunction, including fibrosis is associated with the development of GDM, factors that link these observations remain unknown. Prothymosin α (ProTα) is expressed in the placenta and is involved in cell proliferation and immunomodulation. It also plays an important role in insulin resistance and fibrosis. However, the role of ProTα in GDM is still unclear. In the present study, we found that fibrosis-related protein expressions, such as type I collagen (Col-1) were significantly increased in the placentae of ProTα transgenic mice. With elevated fibrosis-related protein expressions, placental weights significantly increased in GDM group. In addition, placental and circulating ProTα levels were significantly higher in patients with GDM (n=39), compared with the healthy group (n=102), and were positively correlated with Col-1 expression. Mice with streptozotocin (STZ)-induced GDM had increased ProTα, fasting blood glucose, Col-1, and placental weight, whereas plasma insulin levels were decreased. ProTα overexpression enhanced nuclear factor κB (NFκB) activation to increase fibrosis-related protein expressions in 3A-Sub-E trophoblasts, while treatment with an NFκB inhibitor reversed the effect of ProTα on fibrosis-related protein expressions. We further investigated whether ProTα is regulated by hyperglycemia-induced reactive oxygen species (ROS). In conclusion, ProTα increases the amount of placental connective tissue and thus contributes to the pathogenesis of placental fibrosis in GDM. Therefore, ProTα may be a novel therapeutic target for GDM.

Topics: Adult; Animals; Collagen Type I; Diabetes, Gestational; Female; Fibrosis; Gene Expression Regulation; Humans; Hyperglycemia; Inflammation; Mice, Inbred C57BL; Mice, Transgenic; NF-kappa B; Placenta; Pregnancy; Protein Precursors; Reactive Oxygen Species; Signal Transduction; Thymosin; Trophoblasts

To evaluate the efficacy of thymosin beta 4 (Tβ(4)) on hyperglycemia and insulin sensitivity in a mouse model of type 2 diabetes mellitus (T2DM).. KK mice were divided into the following groups: KK control group, with saline treatment; KK Tβ(4) group, with daily Tβ(4) 100ng/10g body weight intraperitoneal injection for 12 weeks. Non-diabetic C57BL mice were used as normal control. OGTT, plasma insulin, HbA1c, serum adiponectin, Tβ(4), cholesterol, and triglyceride were measured before and after Tβ(4) treatment. The phosphorylated AKT and total AKT protein levels of skeletal muscle from all groups were determined.. After Tβ(4) treatment, repeat OGTT showed a significant decrease in glucose profiles in the KK Tβ(4) group compared with the KK control group. The KK-Tβ(4) group had reduced mean HbA1c and triglyceride levels, and increased adiponectin compared with KK control group. C57BL mice showed normal glucose homeostasis. The phosphorylated AKT levels of skeletal muscle were significantly increased in KK Tβ(4) group compared with KK control group after glucose stimulation. C57BL mice showed no changes in phosphorylated AKT levels after Tβ(4) treatment.. Tβ(4) improved glucose intolerance and ameliorated insulin resistance in KK mouse. Tβ(4) may be a potential alternative insulin sensitizer for treatment of T2DM.

Topics: Animals; Blotting, Western; Glucose Tolerance Test; Hyperglycemia; Insulin Resistance; Mice; Thymosin

Protection by thymosin fraction 5 (TF5) from subdiabetogenic-dose streptozotocin (STZ)-induced type I diabetes in CD-1 mice was investigated. Mice which received multiple subdiabetogenic-dose (35 mg/kg) injections of STZ became hyperglycemia within two weeks. Hyperglycemia was also induced in those treated with low dose of TF5 (0.01 mg/day) in addition to STZ, though it was somewhat mild. In contrast, animals given STZ plus high dose of TF5 (0.1 mg/day) remained normoglycemic throughout the whole observation period (within 4 weeks). In the pancreatic islets from these animals, histologically, the well-granulated beta cells were observed and the infiltration of lymphoid cells was absent or mild. These results suggest that the administration of TF5 prevents the induction of insulitis and hyperglycemia in the subdiabetogenic-dose STZ-treated mice.

Topics: Animals; Diabetes Mellitus, Experimental; Hyperglycemia; Islets of Langerhans; Male; Mice; Thymosin

Topics: Aged; Carcinoma, Renal Cell; Drug Evaluation; Humans; Hyperglycemia; Kidney Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Thymosin