Guava Leaf Extract Attenuates Insulin Resistance via the PI3K/Akt Signaling Pathway in a Type 2 Diabetic Mouse Model.

BACKGROUND AND OBJECTIVE: Insulin resistance is well known to exhibit essential effects on the progression of diabetes mellitus (DM). Guava leaf was also reported to exhibit anti-diabetic effects including decreasing blood glucose. Therefore, this present study aims to explore the role guava leaf extract (GLE) plays in insulin resistance and its mechanism of action via the PI3K/Akt signaling pathway. METHODS: KK-Ay mice is a spontaneous genetic type 2 diabetes mouse model induced by feeding a high fat and high sugar diet. Mice were randomly assigned into three groups: diabetic mice (DM), DM + MET (diabetic mice treated with metformin) and DM + GLE (diabetic mice treated with GLE) groups. After 8 weeks of treatment, body weight and levels of fasting plasma glucose (FPG), fasting insulin and lipids in plasma were measured. Mice were sacrificed and mRNA and protein expression of insulin receptor substrate1 (IRS1), phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinase protein B (Akt) in livers were measured. RESULTS: GLE markedly reduced body weight, FPG, fasting insulin and insulin resistance index but increased the insulin sensitivity index of diabetic KK-Ay mice. Moreover, GLE upregulated the expression of IRS-1, PI3K and Akt mRNAs in livers of diabetic KK-Ay mice. In addition, GLE also elevated IRS-1, PI3K, Akt, p-PI3K and p-Akt protein expression in their livers. The results of the DM + MET group were similar to those of the DM + GLE group. CONCLUSION: GLE plays anti-diabetic roles by ameliorating insulin resistance in KK-Ay diabetic mice and this is related to the activation of PI3K/Akt signaling pathway.

The Clinical Significance of Glycoprotein Phospholipase D Levels in Distinguishing Early Stage Latent Autoimmune Diabetes in Adults and Type 2 Diabetes.

Autoantibodies have been widely used as markers of latent autoimmune diabetes in adults (LADA); however, the specificity and sensitivity of autoantibodies as markers of LADA are weak compared with those found in type 1 diabetes (T1DM). In this study, we aimed to identify other plasma proteins as potential candidates that can be used effectively to determine early stage LADA and type 2 diabetes (T2DM) to facilitate early diagnosis and treatment. These issues were addressed by studying new-onset 'classic' T1DM (n = 156), LADA (n = 174), T2DM (n = 195) and healthy cohorts (n = 166). Plasma samples were obtained from the four cohorts. We employed isobaric tag for relative and absolute quantitation (iTRAQ) together with liquid chromatography tandem mass spectrometry (LC-MS) to identify plasma proteins with significant changes in LADA. The changes were validated by Western blot and ELISA analyses. Among the four cohorts, 311 unique proteins were identified in three iTRAQ runs, with 157 present across the three data sets. Among them, 49/311 (16.0%) proteins had significant changes in LADA compared with normal controls, including glycoprotein phospholipase D (GPLD1), which was upregulated in LADA. Western blot and ELISA analyses showed that GPLD1 levels were higher in both LADA and T1DM cohorts than in both T2DM and healthy cohorts, while there were no significant differences in the plasma concentrations of GPLD1 between the LADA and T1DM cohorts. GPLD1 is implicated as a potential candidate plasma protein for determining early stage LADA and T2DM.

Bone marrow plasma macrophage inflammatory protein protein-1 alpha(MIP-1 alpha) and sclerostin in multiple myeloma: relationship with bone disease and clinical characteristics.

The aim of the study was to investigate the expression of MIP-1 alpha and sclerostin in bone marrow of patients with multiple myeloma (MM), the possible association of the sclerostin and MIP-1 alpha with MBD and the clinical characteristics. 53 patients (29 M, 24 F), median age 64 years was studied. MIP-1 alpha, sclerostin and bone-specific alkaline phosphatase (bALP) levels were quantified using an enzyme-linked immunosorbent assay (ELISA). Sclerostin and MIP-1 alpha mRNA expression was determined by RT-PCR. PTH and 1,25(OH) 2D3 levels were measured with an electrochemiluminescence immunoassay. The sclerostin and MIP-1 alpha concentrations in patients with MM were higher than those in the controls. RT-PCR analysis verified that the bone marrow mononuclear cells (BMMNCs) of most patients showed sclerostin and MIP-1 alpha mRNA expression. The sclerostin and MIP-1 alpha levels in patients with ISS stage III disease were significantly higher than those in patients with ISS stage II disease (p=0.01 and 0.06). The sclerostin and MIP-1 alpha levels in patients with BMD in group C were significantly higher than those in group A+B. There was positive correlation between sclerostin levels and MIP-1 alpha, beta2-microglobulin and aCa levels. A negative association was seen between sclerostin levels and bALP, HB and ALB levels. The MM patients with high sclerostin levels (>0.72 ng/ml) had significantly shorter median survival than those with low sclerostin levels (≤0.72 ng/ml) (χ(2)=7.574, p=0.006). Our findings support the positive relationship between sclerostin levels and MIP-1alpha levels deserve further detailed research.

[High glucose lowers insulin receptor substrate 2 expression and induces apoptosis in mouse islet cells in vitro].

OBJECTIVE: To investigate the role of insulin receptor substrate 2 (IRS2) and Bax on mouse islet cell apoptosis in the presence of high glucose in vitro. METHODS: The pancreatic islet cells were isolated from Kunming mice and divided into 6 groups (G1-G6 groups) for a 72-h culture in the media containing different concentrations of glucose (5.6, 7.8, 11.1, 16.7, 22.2, and 27.6 mmol/L, respectively). Insulin secretion by the cells was evaluated by radioimmunoassay, and the expressions of IRS2 and Bax were detected using immunocytochemistry and immunofluorescence assay, respectively. Hoechst33342 staining was employed to observe the cell apoptosis. RESULTS: Exposure to 5.6-11.1 mmol/L glucose resulted in increased insulin secretion and progressive elevation of IRS2 and Bax expression, whereas the cell apoptosis underwent no obvious changes. In the presence of glucose above 16.7 mmol/L, the percentages of apoptotic islet cells increased with glucose concentration, but insulin secretion and IRS2 expression decreased; Bax expression significantly increased in the presence of high-concentration glucose. CONCLUSION: Prolonged exposure of mouse islet cells to high glucose induces apoptosis and impairs insulin secretion of the cells. Decreased IRS2 expression and increased Bax expression may play an important role in the glucotoxicity in mouse islet cells.

[Study on the effect of extraction behaviour of molybdenum (V) thiocyanate complex in the dimethyl sulfoxide and water system by spectrophotometry].

In this paper the effect of petroleum sulfoxide-carbon tetrachloride used as extractant on the extraction behaviour of molybdenum (V) thiocyanate complex at different concentration of dimethyl sulfoxide and water system is studied by spectrophotometry. The mixture ratio of extraction is directly calculated using spectrophotometric data. Functional relation of mixture ratio and concentration of thiocyanate in mixed solution is discussed. By increasing the percent of volume of dimethyl sulfoxide in mixed solution, the effects of mixture ratio and percentage of extraction were studied. The experimental results were explained. It shows that the extraction system of MoO (SCN)3 has an application value.

[Role of cytomegalovirus infection in the pathogenesis of type 2 diabetes mellitus].

OBJECTIVE: To further study the role of human cytomegalovirus (HCMV) infection in the pathogenesis of the type 2 diabetes mellitus. METHODS: HCMV DNA levels in sera from 29 type 2 diabetic patients and 23 controls were measured by quantitative polymerase chain reaction (PCR), and comparative analyses was made between HCMV DNA and T cell subsets, blood glucose (BG), insulin (Ins) and C peptide (C-P). RESULTS: The levels of HCMV DNA were (1.81+/-1.67) x 10(8) copies/ml for type 2 diabetic patients, a level significantly higher than that (5.50+/-4.30) x 10(7) copies/ml of controls. The percentage of CD8 for type 2 diabetic patients with positive HCMV DNA was 29.53%+/-2.00%, being much higher than that for controls (27.13%+/-4.12%), while the ratio of CD4/CD8 1.24+/-0.05 was significantly lower than that 1.41+/-0.10 of controls. Fasting C-P of type 2 diabetic patients with positive HCMV DNA was far lower than that of those with negative HCMV DNA, but the differences of BG and Ins between the two groups were not significant. CONCLUSION: Active HCMV infection of type 2 diabetic patients may suppress cellular immunity and its influence on the pathogenesis of the type 2 diabetes mellitus should be further studied.