ObjectiveTo observe and analyze the correlation between time within target glucose range (TIR) and hemoglobin A1c (HbA1c) and the risk of diabetic retinopathy (DR). MethodsA retrospective clinical study. From March 2020 to August 2021, 91 patients with type 2 diabetes mellitus (T2DM) who were hospitalized in Department of Endocrinology and Metabolic Diseases, Affiliated Hospital of Weifang Medical University, were included in the study. All patients underwent Oburg's no-dilatation ultra-wide-angle laser scan ophthalmoscopy, HbA1c and continuous glucose monitoring (CGM) examinations. According to the examination results and combined with the clinical diagnostic criteria of DR, the patients were divided into non-DR (NDR) group and DR group, with 50 and 41 cases respectively. The retrospective CGM system was used to monitor the subcutaneous interstitial fluid glucose for 7 to 14 consecutive days, and the TIR was calculated. Binary logistic regression was used to analyze the correlation between TIR, HbAlc and DR in patients with T2DM0. At the same time, a new indicator was generated, the predicted probability value (PRE_1), which was generated to represent the combined indicator of TIR and HbA1c in predicting the occurrence of DR. The receiver operating characteristic curve (ROC curve) was used to analyze the value of TIR, HbAlc and PRE_1 in predicting the occurrence of DR. ResultsThe TIR of patients in the NDR group and DR group were (81.58±15.51)% and (67.27±22.09)%, respectively, and HbA1c were (8.03±2.16)% and (9.01±2.01)%, respectively. The differences in TIR and HbA1c between the two groups of patients were statistically significant (t=3.501,－2.208; P=0.001, 0.030). The results of binary logistic regression analysis showed that TIR, HbA1c and DR were significantly correlated (odds ratio=0.960, 1.254; P=0.002, 0.036). ROC curve analysis results showed that the area under the ROC curve (AUC) of TIR, HbA1c and PRE_1 predicting the risk of DR were 0.704, 0.668, and 0.707, respectively [95% confidence interval (CI) 0.597-0.812, P=0.001; 95%CI 0.558-0.778, P=0.006; 95%CI 0.602-0.798, P=0.001]. There was no statistically significant difference between TIR, HbA1c and PRE_1 predicting the AUC of DR risk (P>0.05). The linear equation between HbAlc and TIR was HbAlc (%) = 11.37－0.04×TIR (%). ConclusionsTIR and HbA1c are both related to DR and can predict the risk of DR. The combined use of the two does not improve the predictive value of DR. There is a linear correlation between TIR and HbAlc.
ObjectiveTo elucidate whether hypoxia induced factor-1α (HIF-1α) gene improved hypoxia tolerant capability of bone marrow mesenchymal stem cells uptake(MSCs) or not and whether the capability was related to glucose uptake increase in hypoxia MSCs ex vivo or not. MethodsMSCs were randomly divided into normoxia non-HIF-1α transfection group (control group), normoxia HIF-1α transfection group, hypoxia non-HIF-1α transfection group, and hypoxia HIF-1α transfection group and then each group was cultured with normoxia (5% CO2 at 37 ℃) or hypoxia (94% N2, 1% O2, 5% CO2 at 37 ℃) for 8 h, respectively. Finally, the expressions of HIF-1α were detected by immunocytochemistry, RT-PCR, and Western blot methods, respectively. Apoptosis ratio (AR) and death ratio (DR) were tested by flow cytometry. The proliferation was detected by MTT method. Glucose uptake was assayed by radiation isotope method. Results① Compared with the normoxia non-HIF-1α transfection group, the expression of HIF-1α mRNA significantly increased (Plt;0.01) in the normoxia HIF-1α transfection group except for its protein (P=0.187); Both of mRNA and protein expressions of HIF-1α in the hypoxia HIF-1α transfection group were significantly higher than those in the hypoxia non-HIF-1α transfection group (Plt;0.01). ② The AR (P=0.001) and DR (P=0.003) in the hypoxia HIF-1α transfection group were significantly lower thanthose in the hypoxia non-HIF-1α transfection group, both of which were significantly higher than those in the normoxia non-HIF-1α transfection group (Plt;0.01). ③ The proliferation of MSCs in the hypoxia HIF-1α transfection group was significantly higher than that in the hypoxia non-HIF-1α transfection group (P=0.004), which significantly lower than that in the normoxia non-HIF-1α transfection group (P=0.001). ④ Compared with the hypoxia non-HIF-1α transfection group, the 3H-G uptake capability (P=0.004) of MSCs significantly increased in the hypoxia HIF-1α transfection group, which was significantly lower than that in the normoxia non-HIF-1α transfection group (P=0.001). ⑤ There were significantly negative relation between AR and HIF-1α protein (r=－0.71，P=0.005) or 3H-G uptake (r=－0.65，P=0.004), and significantly positive relation between HIF-1α protein expression and 3H-G uptake (r=0.77, P=0.003). ConclusionHIF-1α gene significantly improves anti-hypoxia capability of MSCs, which is fulfilled by increasing glucose upake.
Objective To summarize the advance of bioenergetic metabolic mechanisms of cancer cell. Methods Literatures about the recent studies on the bioenergetic metabolic mechanisms of cancer cell were reviewed.Results Cancer cells required a steady source of metabolic energy in order to continue their uncontrolled growth and proliferation. Accelerated uptake of glucose and glycolysis was one of the biochemical characteristics of hypoxia cancer cells. Glucose transport and metabolism were essential for the survival of tumor cells, leading to poor prognosis. Conclusions The studies on relationships between hypoxia-inducible genes and cancer have come a new understanding of the bioenergetic metabolic mechanisms of cancer cell, become new and important supplementary means of diagnosis and treatment of cancer, and enhanced existing strategies so that the treatment could be more rationally applied and personalized for cancer patients.
Objective To investigate the effects of expression of TNFα mRNA on glucose uptake in both the liver and skeletal muscle after endotoxemia. Methods In the mice with intraperitoneal injection of lipopolysaccharide (LPS), the changes of TNFα level of plasma and uptake of 2-deoxyglucose (2-DG) in the isolated soleus muscle and hepatic tissues were determined, then the reinstatement of glucose uptake by injecting TNF-McAb for 3 days was also observed. In addition, changes of TNFα mRNA expression of liver were evaluated. Results The expression of TNFα mRNA in the liver showed markedly increased in the first 3 hours post endotoxemia and remaind high for 3 days, and the plasma TNFα level paralleled with TNFα mRNA expression of liver also was elevated. The basal uptake of 2-DG both in muscle and liver were markedly increased, but the stimulated 2-DG uptake with insulin was greatly reduced as compared with the control. In addition, these abnormalities of 2-DG uptake can be partially corrected by neutralization of the circulatory TNFα by administration of TNF-McAb. Conclusion The disorders of glucose uptake of the liver and the muscle due to the overexpression of TNFα mRNA and elevated circulatory TNFα level may be the mechanism of insulin resistance after endotoxemia.
Age-related macular degeneration (AMD) involves dysregulation of the innate immune response of complement and mononuclear phagocytes and abnormalities of local microglia. When microglia transition from a resting state to an active state, their metabolic pathway also changes, known as "metabolic reprogramming", and their glucose metabolic reprogramming is a key factor in the pathogenesis of AMD, involving multiple signaling pathways. Including phosphatidylinositol 3-kinase-serine threonine kinase-rapamycin target, adenylate activated protein kinase and hypoxia-inducing factor 1 pathway. These metabolic changes regulate the inflammatory response, energy supply, and neuroprotective functions of microglia. Therapeutic strategies to regulate the reprogramming of glucose metabolism in microglia have achieved initial results. Future studies should further explore the mechanisms of microglia metabolic regulation to develop new targeted drugs and intervene in the treatment of AMD through anti-cellular aging pathways.
ObjectiveTo explore the expressions of glucose regulated protein (GRP) 78 and GRP94 in rectal adenocarcinoma and their clinical significances. MethodsIn 45 paraffin-embedded sections of rectal adenocarcinoma tissues and adjacent normal tissues, the expressions of GRP78 and GRP94 were examined by EnVisionTM. ResultsThe positive rates of GRP78 and GRP94 protein expression in the rectal adenocarcinoma tissues were 53.33% (24/45) and 53.33% (24/45), while those in the adjacent normal tissues were 13.33% (6/45) and 15.56% (7/45), respectively. There was a statistical significance of the expression of GRP78 or GRP94 between the tumor tissues and the adjacent normal tissues (all P < 0.001), and it was found that the positive expression rates were relevant to the extent of differentiation, Dukes stage, and lymph node metastasis of cancer (all P < 0.05), but not to the patient's sex, age, and size of tumor (all P > 0.05). And there was a statistical significance in Spearman method about the rate of positive expression between GRP78 and GRP94 (rs=0.464, P < 0.01). ConclusionGRP78 and GRP94 protein is highly expressed in rectal adenocarcinoma tissue, related to its metastasis and invasion, might be used as a useful indicator to judge the malignant degree.
ObjectiveTo study the effects of Ghrelin for glucose metabolism and insulin sensitivity of L6 rat myoblasts in palmitic acid induced, and to explore its possible mechanisms. MethodsThe L6 rat myoblasts were cultured until differentiation, then using palmitic acid(0.3 mmol/L) for 16 hours. The experimental group was treated with different doses of Ghrelin(1, 10, and 100 nmol/L) for 8 hours, then the glucose uptake was detected by using glucose oxidase peroxidase method(GOD-POD), the cell membrane glucose transporter 4(GLUT-4) protein staining was observated under confocal microscopy, and the expressions of total protein kinase B(Akt), phosphorylated protein kinase B(pAkt), total glycogen synthase kinase-3β(GSK-3β), and phosphorylated glycogen synthase kinase-3β(pGSK-3β) were detected by using immunoblotting(Western blot). ResultsGhrelin enhanced the glucose uptake of L6 rat myoblasts with insulin resistance, the cell membrane Glut-4 stain was deepen, the expressions of pAkt and pGSK-3βprotein increased, and this effect could be PI3K blocker(LY294002) eliminated. ConclusionGhrelin promotes the glucose uptake of L6 rat myoblasts through PI3K/Akt/GSK-3βsignaling pathway, so as to improve the sensitivity of insulin in L6 rats muscle cells.
ObjectiveTo investigate the prevalence of impaired glucose regulation (IGR) and IGR combined with cardiovascular risk factors in rural areas of Chengdu City. MethodsFrom February to October 2010, we randomly sampled 1 016 patients in a rural community 100 kilometers away from the city center as the study subjects. The investigation was carried out by using questionnaire survey, physical examination and laboratory tests. The standard 75 g oral glucose tolerance test was used. ResultsA total of 1 016 subjects were investigated, among whom there were 431 males and 585 females with an average age of 56 years old. Of these subjects, 333 were diagnosed to have IGR with a rate of 32.77% (333/1 016). The age-adjusted standardized prevalence of pre-diabetes in rural areas in Chengdu was 32.52% (336/1 016), and the male and female prevalence were respectively 30.63% (132/431) and 34.36% (201/585) without significant difference (χ2=1.569，P=0.210). Impaired glucose tolerance (IGT) was the most common type of glycometabolism abnormality. Women had a significantly higher prevalence of IGT than men. In IGR population, major cardiovascular risk factors were overweight and obesity (40.8%), high low density lipoprotein cholesterol (38.4%), high triglyceride (30.3%), hypertension (23.7%), smoking (24.3%), and drinking alcohol (23.7%). The stratified analysis showed that the prevalence of overweight, obesity and low high density lipoprotein cholesterol in female was significantly higher than that in males, while the prevalence of smoking and drinking alcohol was significantly higher in males. ConclusionIn rural areas, the prevalence of pre-diabetes is high and complicated with multiple cardiovascular risk factors.
Objective To study the effects of glucose and lipid metabolism on gallstone formation. Methods Twenty five patients with gallstones and 25 normal volunteer controls were studied from January to April in 1998. The patients were well matched the control with sex and age (1∶1). In the study, Body Mass Index (BMI) and Waist-to-Hip circumference ratio (W/H) were measured. Blood glucose, glucosylated hemoglobin (HbA1C), insulin, C peptide and all parameters of lipids were detected at fasting state. The glucose,insulin, C peptide were detected again at 2-hour after taking 75g glucose orally.Results The result showed there was no difference on BMI and W/H between the patients and controls. HbA1C、mean fasting and 2hour glucose concentration were not in significantly different between the two groups (Pgt;0.05, Pgt;0.2, Pgt;0.1 respectively). There were 10 patients with abnormal glucose metabolism (7 with NIDDM, 3 with IGT), but only 4 controls were abnoumal (one with NIDDM, three with IGT). The difference was significant (Plt;0.05). Furthermore, the mean fasting and 2hour insulin concentration of gallstone group was higher than that of the control (Plt;0.02, Plt;0.05). And the gallstone group had a higher fasting C peptide concentration than control (Plt;0.05). There was no statistical difference on the parameters of plasma lipid between the tow groups. Conclusion The study suggests that diabetes mellious and hyperinsulinemia acted as an important role on gallstone formation.
Objective To investigate the expression of aquaporin-1( AQP-1) in pleural mesothelial cells ( PMCs) and the influence of glucose thereupon. Methods Rat PMCs were isolated, cultured, and divided into two groups, ie. a glucose group, cultured with glucose of different concentrations for 24 hours,and a control group, cultured in D-MEM/ F-12 medium. The 100 mmol / L glucose group was administered at the time points of 6, 12, 18, and 24 hours respectively. RT-PCR and Western blotting were used to analyze the mRNA and protein expression of AQP-1. Results The absorbance values of AQP-1 protein expression were 54. 02 ±4. 61, 127. 84 ±9. 41, and 231. 62 ±22. 63, respectively in the PMCs treated with glucose of the concentrations of 50, 100, and 200 mmol / L, all significantly higher than those in the control group( 22. 45 ±2. 16, all P lt; 0. 01) . The absorbance values of AQP-1 protein expression were 24. 68 ±2. 56, 58. 68 ±3. 67, 89. 61 ±6. 62, and 113. 41 ±7. 65 in the PMCs treated with glucose of the concentration of 100 mmol / L after 6, 12, 18, and 24 hours, all significantly higher than those in the control group ( 11. 81 ±1. 45, P lt;0. 01) .Conclusions Glucose induces the expression of AQP-1 mRNA and protein. AQP-1 participates in the pleural fluid formation.