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Med Sci Monit ; 25: 9679-9689, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31848329


BACKGROUND The aim of this study was to determine the association between white matter lesions (WML) and diabetes-associated cognitive decline (DACD) in rat models of type 2 diabetes (T2DM). MATERIAL AND METHODS Sixty Sprague-Dawley male rats were divided into 4 groups: control, control+metformin, T2DM, and T2DM+metformin groups. The T2DM groups were fed a diet high in fat and glucose to induce impaired glucose tolerance (IGT) and then were injected with streptozotocin to induce T2DM. The Morris water maze test was used to evaluate cognitive function. Brain diffusion tensor imaging scans were performed for WML. The expression of myelin basic protein (MBP), oligodendrocyte transcription factor 1 (OLIG1), and OLIG2 (markers of brain damage and repair) was determined using immunofluorescence. After IGT, the fractional anisotropy (FA) values of the right thalamus area were significantly lower in both T2DM groups compared with controls. RESULTS Eight weeks after streptozotocin injection, the FA values of the thalamus were lower in the T2DM (bilateral thalamus) group and T2DM+metformin (left thalamus) group than in controls, while the FA values in the left thalamus area were lower in the T2DM+metformin group than in the control and control+metformin groups. The maze escape latency was longer and the number of rats passing through the platform was smaller in the T2DM and T2DM+metformin groups than in the control group. MBP levels were lower and OLIG1 and OLIG2 levels were higher in both T2DM groups than in controls. CONCLUSIONS WML is associated with DACD and appears before the onset of T2DM and signs of DACD and plays a role in diabetes-associated cognitive decline. Metformin reduces WMLs but does not rescue cognitive dysfunction.

Endocr J ; 64(8): 787-796, 2017 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-28674284


C1qTNF-related protein 1 (CTRP1) is independently associated with type 2 diabetes. However, the relationship between CTRP1 and insulin resistance is still not established. This study aimed to explore the role of CTRP1 under the situation of insulin resistance in adipose tissue. Plasma CTRP1 level was investigated in type 2 diabetic subjects (n = 35) and non-diabetic subjects (n = 35). The relationship between CTRP1 and phosphorylation of multi insulin receptor substrate 1 (IRS-1) serine (Ser) sites was further explored. Our data showed that Plasma CTRP1 was higher and negative correlation with insulin resistance in diabetic subjects (r = -0.283, p = 0.018). Glucose utilisation test revealed that the glucose utilisation rate of mature adipocytes was improved by CTRP1 in the presence of insulin. CTRP1 was not only related to IRS-1 protein, but also negatively correlated with IRS-1 Ser1101 phosphorylation (r = -0.398, p = 0.031). Furthermore, Phosphorylation levels of IRS-1 Ser1101 were significantly lower after incubation with 40 ng/mL CTRP1 in mature adipocytes than those with no intervention (p < 0.05). There was no significant correlation between CTRP1 and other IRS-1 serine sites (Ser302, Ser307, Ser612, Ser636/639, and Ser789). Collectively, our results suggested that CTRP1 might improve insulin resistance by reducing the phosphorylation of IRS-1 Ser1101, induced in the situation of insulin resistance as a feedback adipokine.

Diabetes Mellitus Tipo 2/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina/fisiologia , Proteínas/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adulto , Idoso , Feminino , Humanos , Insulina/farmacologia , Masculino , Pessoa de Meia-Idade , Fosforilação/efeitos dos fármacos , Proteínas/farmacologia , Transdução de Sinais/efeitos dos fármacos
Endocr J ; 61(9): 841-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24965225


Complement C1q tumor necrosis factor-related protein 1 (CTRP1), an adipose tissue-derived adipokine has been shown to decrease blood glucose levels and to improve metabolism of glucose in mice. In addition, CTRP1 has exhibited significant association with BMI, adiponectin and TNF-α in diabetic animal models. However, there are no published studies addressing CTRP1 levels in type 2 diabetic patients. Therefore, it was of interest to evaluate plasma CTRP1 levels and associated clinical parameters and biomarkers in patients with type 2 diabetes. 135 subjects were recruited to this study, including 62 type 2 diabetic patients (DM group) and 73 healthy subjects (control group). We measured biochemical parameters, CTRP1, TNF-α and adiponectin using enzyme-linked immunosorbent assay (ELISA). Plasma CTRP1 levels showed a significant difference between the DM group and the control group (646.3 ± 154.4 ng/mL vs. 442.6 ± 165.4 ng/mL, p < 0.01). In addition, CTRP1 was strongly positively associated with BMI, glucose levels, HbA1c, HOMA-IR and TNF-α in diabetic patients. CTRP1 showed negative correlation with adiponectin. In Multivariate regression analysis, CTRP1 was strongly independently associated with diabetes when CTRP1 levels were analyzed by both as a continuous variable and quartile (OR: 1.009, 95% CI: 1.004-1.015, p < 0.05; OR: 2.443, 95% CI: 1.379-4.182, p < 0.01, respectively). Increased plasma CTRP1 was independently associated with type 2 diabetes. Profiling of plasma adipokines such as CTRP1 is particularly important to obtain a greater understanding of their contribution to the type 2 diabetic state.

Diabetes Mellitus Tipo 2/sangue , Proteínas/metabolismo , Adipocinas , Adiponectina/sangue , Adulto , Idoso , Biomarcadores/sangue , Glicemia , Índice de Massa Corporal , Feminino , Hemoglobina A Glicada/metabolismo , Homeostase , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Fator de Necrose Tumoral alfa/sangue
Med Hypotheses ; 71(6): 889-91, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18786775


Sulfonylureas, by stimulating beta cell to secrete insulin, are still largely used for treatment of type 2 diabetic patients. More recently concern has been raised with respect to possible adverse effects associated with the use of these agents, like favoring beta cell apoptosis and beta cell exhaustion, which is believed as the reason for high rate secondary sulfonylurea failure. Endoplasmic reticulum (ER) stress often occurred when load of client protein exceed the folding capacity in secretory cell. Here, we hypothesize that overstimulation by chronic use of sulfonylureas could probably leads to ER stress and finally apoptosis in beta cell, which might be the latent mechanism for secondary sulfonylurea failure.

Diabetes Mellitus Tipo 2/tratamento farmacológico , Retículo Endoplasmático/fisiologia , Células Secretoras de Insulina/fisiologia , Compostos de Sulfonilureia/uso terapêutico , Apoptose/efeitos dos fármacos , Diabetes Mellitus Tipo 2/fisiopatologia , Humanos , Hipoglicemiantes/uso terapêutico , Células Secretoras de Insulina/efeitos dos fármacos , Modelos Biológicos , Falha de Tratamento