Chronic Hyperglycemia and Glucose Toxicity: Pathology and Clinical Sequelae

2012 ◽  
Vol 124 (6) ◽  
pp. 90-97 ◽  
Author(s):  
Carlos Campos
2008 ◽  
Vol 295 (1) ◽  
pp. E17-E28 ◽  
Author(s):  
Ronald J. Copeland ◽  
John W. Bullen ◽  
Gerald W. Hart

O-linked β- N-acetylglucosamine ( O-GlcNAc) is a dynamic posttranslational modification that, analogous to phosphorylation, cycles on and off serine and/or threonine hydroxyl groups. Cycling of O-GlcNAc is regulated by the concerted actions of O-GlcNAc transferase and O-GlcNAcase. GlcNAcylation is a nutrient/stress-sensitive modification that regulates proteins involved in a wide array of biological processes, including transcription, signaling, and metabolism. GlcNAcylation is involved in the etiology of glucose toxicity and chronic hyperglycemia-induced insulin resistance, a major hallmark of type 2 diabetes. Several reports demonstrate a strong positive correlation between GlcNAcylation and the development of insulin resistance. However, recent studies suggest that inhibiting GlcNAcylation does not prevent hyperglycemia-induced insulin resistance, suggesting that other mechanisms must also be involved. To date, proteomic analyses have identified more than 600 GlcNAcylated proteins in diverse functional classes. However, O-GlcNAc sites have been mapped on only a small percentage (<15%) of these proteins, most of which were isolated from brain or spinal cord tissue and not from other metabolically relevant tissues. Mapping the sites of GlcNAcylation is not only necessary to elucidate the complex cross-talk between GlcNAcylation and phosphorylation but is also key to the design of site-specific mutational studies and necessary for the generation of site-specific antibodies, both of which will help further decipher O-GlcNAc's functional roles. Recent technical advances in O-GlcNAc site-mapping methods should now finally allow for a much-needed increase in site-specific analyses to address the functional significance of O-GlcNAc in insulin resistance and glucose toxicity as well as other major biological processes.


Diabetes ◽  
1994 ◽  
Vol 43 (9) ◽  
pp. 1085-1089 ◽  
Author(s):  
R. P. Robertson ◽  
L. K. Olson ◽  
H. J. Zhang

2019 ◽  
Vol 25 (23) ◽  
pp. 2602-2606 ◽  
Author(s):  
Shahzad Khan ◽  
Mohammad A. Kamal

: Insulin resistance and type 2 Diabetes mellitus resulting in chronic hyperglycemia is a major health problem in the modern world. Many drugs have been tested to control hyperglycemia which is believed to be the main factor behind many of the diabetes-related late-term complications. Wogonin is a famous herbal medicine which has been shown to be effective in controlling diabetes and its complications. In our previous work, we showed that wogonin is beneficial in many ways in controlling diabetic cardiomyopathy. In this review, we mainly explained wogonin anti-hyperglycemic property through AKT/GLUT4 pathway. Here we briefly discussed that wogonin increases Glut4 trafficking to plasma membrane which allows increased entry of glucose and thus alleviates hyperglycemia. Conclusion: Wogonin can be used as an anti-diabetic and anti-hyperglycemic drug and works via AKT/GLUT4 pathway.


2019 ◽  
Vol 19 (9) ◽  
pp. 688-698 ◽  
Author(s):  
Azam Roohi ◽  
Mahin Nikougoftar ◽  
Hamed Montazeri ◽  
Shadisadat Navabi ◽  
Fazel Shokri ◽  
...  

Background: Oxidative stress and chronic hyperglycemia are two major side effects of type 2 diabetes affecting all cell types including mesenchymal stem cells (MSCs). As a cell therapy choice, understanding the behavior of MSCs will provide crucial information for efficient treatment. Methods: Placental mesenchymal stem cells were treated with various concentrations of glucose, metformin, rapamycin, and hydrogen peroxide to monitor their viability and cell cycle distribution. Cellular viability was examined via the MTT assay. Cell cycle distribution was studied by propidium iodide staining and apoptosis was determined using Annexin Vpropidium iodide staining and flow cytometry. Involvement of potential signaling pathways was evaluated by Western blotting for activation of Akt, P70S6K, and AMPK. Results: The results indicated that high glucose augmented cell viability and reduced metformin toxic potential. However, the hydrogen peroxide and rapamycin toxicities were exacerbated. Conclusion: Our findings suggest that high glucose concentration has a major effect on placental mesenchymal stem cell viability in the presence of rapamycin, metformin and hydrogen peroxide in culture.


Author(s):  
Anagha Gosavi ◽  
Ram V. Ramekar

Prameha is disease of Mutravaha Srotasa having Kapha dominancy which can be correlated with diabetes mellitus. The term diabetes mellitus describes a metabolic disorder of multiple etiologies characterized by chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. Madhumeha is considered as a subtype under the Vatika type of Prameha and it is characterized by passage of urine with sweet taste like honey along with sweetness of whole body. With appropriate use of Ayurvedic preventive measures such as Dincharya, Ritucharya, Aharvidhi and therapeutic measures Madhumeha (DM) can be prevented.


2021 ◽  
Vol 11 (4) ◽  
pp. 1742
Author(s):  
Ignacio Rodríguez-Rodríguez ◽  
José-Víctor Rodríguez ◽  
Wai Lok Woo ◽  
Bo Wei ◽  
Domingo-Javier Pardo-Quiles

Type 1 diabetes mellitus (DM1) is a metabolic disease derived from falls in pancreatic insulin production resulting in chronic hyperglycemia. DM1 subjects usually have to undertake a number of assessments of blood glucose levels every day, employing capillary glucometers for the monitoring of blood glucose dynamics. In recent years, advances in technology have allowed for the creation of revolutionary biosensors and continuous glucose monitoring (CGM) techniques. This has enabled the monitoring of a subject’s blood glucose level in real time. On the other hand, few attempts have been made to apply machine learning techniques to predicting glycaemia levels, but dealing with a database containing such a high level of variables is problematic. In this sense, to the best of the authors’ knowledge, the issues of proper feature selection (FS)—the stage before applying predictive algorithms—have not been subject to in-depth discussion and comparison in past research when it comes to forecasting glycaemia. Therefore, in order to assess how a proper FS stage could improve the accuracy of the glycaemia forecasted, this work has developed six FS techniques alongside four predictive algorithms, applying them to a full dataset of biomedical features related to glycaemia. These were harvested through a wide-ranging passive monitoring process involving 25 patients with DM1 in practical real-life scenarios. From the obtained results, we affirm that Random Forest (RF) as both predictive algorithm and FS strategy offers the best average performance (Root Median Square Error, RMSE = 18.54 mg/dL) throughout the 12 considered predictive horizons (up to 60 min in steps of 5 min), showing Support Vector Machines (SVM) to have the best accuracy as a forecasting algorithm when considering, in turn, the average of the six FS techniques applied (RMSE = 20.58 mg/dL).


2021 ◽  
Vol 22 (15) ◽  
pp. 7917
Author(s):  
Hideaki Kaneto ◽  
Tomohiko Kimura ◽  
Masashi Shimoda ◽  
Atsushi Obata ◽  
Junpei Sanada ◽  
...  

Fundamental pancreatic β-cell function is to produce and secrete insulin in response to blood glucose levels. However, when β-cells are chronically exposed to hyperglycemia in type 2 diabetes mellitus (T2DM), insulin biosynthesis and secretion are decreased together with reduced expression of insulin transcription factors. Glucagon-like peptide-1 (GLP-1) plays a crucial role in pancreatic β-cells; GLP-1 binds to the GLP-1 receptor (GLP-1R) in the β-cell membrane and thereby enhances insulin secretion, suppresses apoptotic cell death and increase proliferation of β-cells. However, GLP-1R expression in β-cells is reduced under diabetic conditions and thus the GLP-1R activator (GLP-1RA) shows more favorable effects on β-cells at an early stage of T2DM compared to an advanced stage. On the other hand, it has been drawing much attention to the idea that GLP-1 signaling is important in arterial cells; GLP-1 increases nitric oxide, which leads to facilitation of vascular relaxation and suppression of arteriosclerosis. However, GLP-1R expression in arterial cells is also reduced under diabetic conditions and thus GLP-1RA shows more protective effects on arteriosclerosis at an early stage of T2DM. Furthermore, it has been reported recently that administration of GLP-1RA leads to the reduction of cardiovascular events in various large-scale clinical trials. Therefore, we think that it would be better to start GLP-1RA at an early stage of T2DM for the prevention of arteriosclerosis and protection of β-cells against glucose toxicity in routine medical care.


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