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1.
The glucose uptake systems in Corynebacterium glutamicum: a review.
Ruan, H, Yu, H, Xu, J
World journal of microbiology & biotechnology. 2020;(9):126
Abstract
The phosphoenolpyruvate-dependent glucose phosphotransferase system (PTSGlc) is the major uptake system responsible for transporting glucose, and is involved in glucose translocation and phosphorylation in Corynebacterium glutamicum. For the longest time, the PTSGlc was considered as the only uptake system for glucose. However, some PTS-independent glucose uptake systems (non-PTSGlc) were discovered in recent years, such as the coupling system of inositol permeases and glucokinases (IPGS) and the coupling system of β-glucoside-PTS permease and glucokinases (GPGS). The products (e.g. lysine, phenylalanine and leucine) will be increased because of the increasing intracellular level of phosphoenolpyruvate (PEP), while some by-products (e.g. lactic acid, alanine and acetic acid) will be reduced when this system become the main uptake pathway for glucose. In this review, we survey the uptake systems for glucose in C. glutamicum and their composition. Furthermore, we summarize the latest research of the regulatory mechanisms among these glucose uptake systems. Detailed strategies to manipulate glucose uptake system are addressed based on this knowledge.
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2.
Metabolic and functional specialisations of the pancreatic beta cell: gene disallowance, mitochondrial metabolism and intercellular connectivity.
Rutter, GA, Georgiadou, E, Martinez-Sanchez, A, Pullen, TJ
Diabetologia. 2020;(10):1990-1998
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Abstract
All forms of diabetes mellitus involve the loss or dysfunction of pancreatic beta cells, with the former predominating in type 1 diabetes and the latter in type 2 diabetes. Deeper understanding of the coupling mechanisms that link glucose metabolism in these cells to the control of insulin secretion is therefore likely to be essential to develop new therapies. Beta cells display a remarkable metabolic specialisation, expressing high levels of metabolic sensing enzymes, including the glucose transporter GLUT2 (encoded by SLC2A2) and glucokinase (encoded by GCK). Genetic evidence flowing from both monogenic forms of diabetes and genome-wide association studies for the more common type 2 diabetes, supports the importance for normal glucose-stimulated insulin secretion of metabolic signalling via altered ATP generation, while also highlighting unsuspected roles for Zn2+ storage, intracellular lipid transfer and other processes. Intriguingly, genes involved in non-oxidative metabolic fates of the sugar, such as those for lactate dehydrogenase (LDHA) and monocarboxylate transporter-1 ([MCT-1] SLC16A1), as well as the acyl-CoA thioesterase (ACOT7) and others, are selectively repressed ('disallowed') in beta cells. Furthermore, mutations in genes critical for mitochondrial oxidative metabolism, such as TRL-CAG1-7 encoding tRNALeu, are linked to maternally inherited forms of diabetes. Correspondingly, impaired Ca2+ uptake into mitochondria, or collapse of a normally interconnected mitochondrial network, are associated with defective insulin secretion. Here, we suggest that altered mitochondrial metabolism may also impair beta cell-beta cell communication. Thus, we argue that defective oxidative glucose metabolism is central to beta cell failure in diabetes, acting both at the level of single beta cells and potentially across the whole islet to impair insulin secretion. Graphical abstract.
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3.
High glucose load and endotoxemia among overweight and obese Arab women with and without diabetes: An observational study.
Al-Disi, D, Ansari, MGA, Sabico, S, Wani, K, Hussain, SD, Elshafie, MM, McTernan, P, Al-Daghri, NM
Medicine. 2020;(46):e23211
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Abstract
Dietary intake influences gut microbiota activity. Nevertheless, there is a lack of evidence available that illustrates the acute effects of high glucose meal on metabolic endotoxemia. The present study assessed the acute impact of high glucose meal on endotoxemia and other clinical parameters in Saudi females with varying degrees of glycemia.The subjects were 64 consenting pre-menopausal women, grouped into 3: control [n = 14 lean, non-T2DM, BMI = 22.2 ± 2.2 kg/m]; overweight [n = 16, non-T2DM, BMI = 28.5 ± 1.5 kg/m] and T2DM [n = 34, BMI = 35.2 ± 7.7 kg/m]. After an overnight fast, all subjects were given a standardized high-glucose (75 g) meal. Anthropometrics were taken and blood samples were withdrawn at baseline and postprandial (0, 2 and 4-hours), serum glucose, endotoxin and lipid profile were quantified.At baseline, total cholesterol, LDL-cholesterol, triglycerides and serum glucose levels were significantly higher (P values <.01) whereas significantly lower HDL-cholesterol levels (P < .01) were observed in T2DM subjects compared to other groups. Baseline endotoxin levels were highest in the overweight group (3.2 ± 1.1 mmol/L) as compared to control (2.0 ± 0.5 mmol/L) and T2DM (2.7 ± 1.2 mmol/L) (P = .046). HDL-cholesterol, LDL-cholesterol and triglycerides, significantly decreased in the T2DM group after 2 hours (P values <.05), whereas unremarkable changes observed in other groups. Lastly, endotoxin levels significantly increased only in the overweight group (3.2 ± 1.1 vs 4.2 ± 1.4 mmol/L; P < .05), 4 hours postprandial.High glucose meal elevates endotoxemia only among overweight subjects and impairs dysbiosis.
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Recent progress in the structure of glycogen serving as a durable energy reserve in bacteria.
Wang, L, Wang, M, Wise, MJ, Liu, Q, Yang, T, Zhu, Z, Li, C, Tan, X, Tang, D, Wang, W
World journal of microbiology & biotechnology. 2020;(1):14
Abstract
Glycogen is conventionally considered as a transient energy reserve that can be rapidly synthesized for glucose accumulation and mobilized for ATP production. However, this conception is not completely applicable to prokaryotes due to glycogen structural heterogeneity. A number of studies noticed that glycogen with small average chain length gc in bacteria has the potential to degrade slowly, which might prolong bacterial environment survival. This phenomenon was previously examined and later formulated as the durable energy storage mechanism hypothesis. Although recent research has been warming to the hypothesis, experimental validation is still missing at current stage. In this review, we summarized recent progress of the hypothesis, provided a supporting mathematical model, and explored the technical pitfalls that shall be avoided in glycogen study.
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Stimulation of ORAI1 expression, store-operated Ca2+ entry, and osteogenic signaling by high glucose exposure of human aortic smooth muscle cells.
Ma, K, Sukkar, B, Zhu, X, Zhou, K, Cao, H, Voelkl, J, Alesutan, I, Nürnberg, B, Lang, F
Pflugers Archiv : European journal of physiology. 2020;(8):1093-1102
Abstract
Diabetes and chronic kidney disease (CKD) both trigger vascular osteogenic signaling and calcification leading to early death by cardiovascular events. Osteogenic signaling involves upregulation of the transcription factors CBFA1, MSX2, and SOX9, as well as alkaline phosphatase (ALP), an enzyme fostering calcification by degrading the calcification inhibitor pyrophosphate. In CKD, osteogenic signaling is triggered by hyperphosphatemia, which upregulates the serum and glucocorticoid-inducible kinase SGK1, a strong stimulator of the Ca2+-channel ORAI1. The channel is activated by STIM1 and accomplishes store-operated Ca2+-entry (SOCE). The present study explored whether exposure of human aortic smooth muscle cells (HAoSMCs) to high extracellular glucose concentrations similarly upregulates ORAI1 and/or STIM1 expression, SOCE, and osteogenic signaling. To this end, HAoSMCs were exposed to high extracellular glucose concentrations (15 mM, 24 h) without or with additional exposure to the phosphate donor ß-glycerophosphate. Transcript levels were estimated using qRT-PCR, protein abundance using Western blotting, ALP activity using a colorimetric assay kit, calcium deposits utilizing Alizarin red staining, cytosolic Ca2+-concentration ([Ca2+]i) by Fura-2-fluorescence, and SOCE from increase of [Ca2+]i following re-addition of extracellular Ca2+ after store depletion with thapsigargin (1 μM). As a result, glucose enhanced the transcript levels of SGK1 and ORAI1, ORAI2, and STIM2, protein abundance of ORAI1, SOCE, the transcript levels of CBFA1, MSX2, SOX9, and ALPL, as well as calcium deposits. Moreover, glucose significantly augmented the stimulating effect of ß-glycerophosphate on transcript levels of SGK1 and ORAI1, SOCE, the transcript levels of osteogenic markers, as well as calcium deposits. ORAI1 inhibitor MRS1845 (10 μM) significantly blunted the glucose-induced upregulation of the CBFA1 and MSX2 transcript levels. In conclusion, the hyperglycemia of diabetes stimulates expression of SGK1 and ORAI1, thus, augmenting store-operated Ca2+-entry and osteogenic signaling in HAoSMCs.
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Cellular mechanisms governing glucose-dependent insulinotropic polypeptide secretion.
Reimann, F, Diakogiannaki, E, Hodge, D, Gribble, FM
Peptides. 2020;:170206
Abstract
Glucose-dependent insulinotropic polypeptide (GIP) is a gut hormone secreted from the upper small intestine, which plays an important physiological role in the control of glucose metabolism through its incretin action to enhance glucose-dependent insulin secretion. GIP has also been implicated in postprandial lipid homeostasis. GIP is secreted from enteroendocrine K-cells residing in the intestinal epithelium. K-cells sense a variety of components found in the gut lumen following food consumption, resulting in an increase in plasma GIP signal dependent on the nature and quantity of ingested nutrients. We review the evidence for an important role of sodium-coupled glucose uptake through SGLT1 for carbohydrate sensing, of free-fatty acid receptors FFAR1/FFAR4 and the monoacyl-glycerol sensing receptor GPR119 for lipid detection, of the calcium-sensing receptor CASR and GPR142 for protein sensing, and additional modulation by neurotransmitters such as somatostatin and galanin. These pathways have been identified through combinations of in vivo, in vitro and molecular approaches.
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Impact of flash glucose monitoring on glycaemic control and quality of life in patients with type 1 diabetes: A 18-month follow-up in real life.
Rouhard, S, Buysschaert, M, Alexopoulou, O, Preumont, V
Diabetes & metabolic syndrome. 2020;(2):65-69
Abstract
We conducted a prospective observational study to evaluate the medium-term impact of the flash glucose monitoring system (FGM) in a type 1 diabetic population. We included 248 patients, switched from conventional blood glucose monitoring (BGM) to FGM. We evaluated glycaemic control at 2-4 (T1) and 5-11 (T2) months after initiation and at the last available visit (T3, 18 ± 4 months). We asked patients to fill in, at T0 and T2, two questionnaires based on the Diabetes Treatment Satisfaction Questionnaire; and on the Hypoglycaemia Fear Survey. Glycaemic control improved, from 8.1 ± 1.3% at T0 to 7.8 ± 1.2% at T1 (p < 0.001) and remained unchanged after. Average number of controls increased from 3.2 ± 1.2 BGM to 7.7 ± 3.9 at T1 (p < 0.001). We observed a modest decrease in daily insulin doses. We evidenced an increase in mild hypoglycaemic events, especially in well-controlled subjects, but no increase of severe events. Satisfaction score improved from 30.5 ± 7.7 points to 38.3 ± 5.1 points (p = 0.018), was correlated with the reduction in and was higher in less controlled patients at inclusion. "Behaviour" score regarding hypoglycaemias decrease from 5.7 ± 4.1 to 4.4 ± 3.6 points (p < 0.001). In conclusion, this 18-months study trial indicates that using the FGM technology in patients with T1D may improve glycaemic control, in real-life conditions, especially in less controlled patients. FGM was associated with an increase of patients' satisfaction regarding treatment. Hypoglycaemic events, however, were not reduced in frequency. Therefore, the need for an educational team and a structure program in the management of this new technology remains mandatory.
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8.
Dialysate glucose response phenotypes during peritoneal equilibration test and their association with cardiovascular death: A cohort study.
Wang, Z, Yu, D, Cai, Y, Ma, S, Zhao, B, Zhao, Z, Simmons, D
Medicine. 2020;(21):e20447
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Abstract
Different measures of rates of transfer of glucose during the peritoneal equilibrium test (PET), undertaken during peritoneal dialysis (PD) might provide additional information regarding a patient's risk of future cardiovascular mortality. This study aimed to characterize the heterogeneity of dialysate glucose (DG) response phenotypes during the PET and compare the cardiovascular mortality rates associated with the different phenotypes. Our cohort was derived from Henan peritoneal dialysis registry. A total of 3477 patients initiating PD in 2007 to 2014 had the DG measured at 0, 2-hour and 4-hour (D0, D2, and D4 respectively) during the PET for estimation of D2/D0 and D4/D0. Deaths mainly due to CVD within 2 years since the initiation of PD were defined as the outcome. Latent class mixed-effect models were fitted to identify distinct phenotypes of the DG response during the PET. Multivariable unconditional Logistic regression models with adjustment for cardiometabolic risk factors were used to compare the 2-year risk of cardiovascular mortality among patients in the different latent classes. Three distinct DG response phenotypes during the PET were identified. Those with consistently high D2/D0 and D4/D0 ratios had a 1.22 [95% confidence interval: 1.02, 1.35] excess risk of a cardiovascular death within 2 years of commencing PD compared with patients with the lowest D2/D0 ratio and decreased D4/D0 ratio after adjustment for cardiometabolic risk factors. Consistently elevated D2/D0 and D4/D0 ratios during the PET are associated with an increased risk of 2-year cardiovascular mortality independent of other cardiometabolic risk factors. In view of the potential bias due to unmeasured confounders (eg, Family history of cardiovascular diseases, and dietary patterns), this association should be further validated in other external cohorts.
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New-onset glucose disorders in peritoneal dialysis patients: a meta-analysis and systematic review.
Xue, C, Gu, YY, Cui, CJ, Zhou, CC, Wang, XD, Ruan, MN, Huang, LX, Chen, SX, Yang, B, Chen, XJ, et al
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020;(8):1412-1419
Abstract
BACKGROUND Peritoneal dialysis (PD) patients are at high risk of developing glucose metabolism disturbance (GMD). The incidence and prevalence of new-onset GMD, including diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fast glucose (IFG), after initiation of PD, as well as their correlated influence factors, varies among studies in different areas and of different sample sizes. Also, the difference compared with hemodialysis (HD) remained unclear. Thus we designed this meta-analysis and systematic review to provide a full landscape of the occurrence of glucose disorders in PD patients. METHODS We searched the MEDLINE, Embase, Web of Science and Cochrane Library databases for relevant studies through September 2018. Meta-analysis was performed on outcomes using random effects models with subgroup analysis and sensitivity analysis. RESULTS We identified 1124 records and included 9 studies involving 13 879 PD patients. The pooled incidence of new-onset DM (NODM) was 8% [95% confidence interval (CI) 4-12; I2 = 98%] adjusted by sample sizes in PD patients. Pooled incidence rates of new-onset IGT and IFG were 15% (95% CI 3-31; I2 = 97%) and 32% (95% CI 27-37), respectively. There was no significant difference in NODM risk between PD and HD [risk ratio 0.99 (95% CI 0.69-1.40); P = 0.94; I2 = 92%]. PD patients with NODM were associated with an increased risk of mortality [hazard ratio 1.06 (95% CI 1.01-1.44); P < 0.001; I2 = 92.5%] compared with non-DM PD patients. CONCLUSIONS Around half of PD patients may develop a glucose disorder, which can affect the prognosis by significantly increasing mortality. The incidence did not differ among different ethnicities or between PD and HD. The risk factor analysis did not draw a definitive conclusion. The glucose tolerance test should be routinely performed in PD patients.
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Improvement of glucose metabolism in pregnant women through probiotic supplementation depends on gestational diabetes status: meta-analysis.
Łagowska, K, Malinowska, AM, Zawieja, B, Zawieja, E
Scientific reports. 2020;(1):17796
Abstract
The aim of this study was to assess the effects of probiotic and synbiotic supplementation on glucose metabolism in pregnant women using data from randomized controlled trials. Furthermore, this meta-analysis examines whether the observed effects depend on the presence or absence of gestational diabetes mellitus (GDM), and if the effect is dependent on the type of supplement used (probiotic or synbiotic). We performed a literature search of databases (Medline, Scopus, Web of Knowledge, and Cochrane Library) and identified all relevant randomized controlled trials (RCTs) published prior to May 2019. We compared the effects of probiotic supplementation with the administration of placebos in pregnant women with and without GDM. The systematic review and meta-analysis protocol were registered in the International Prospective Register of Systematic Reviews as number CRD 42019111467. 1119 study participants from 15 selected studies were included. The participants in four studies did not have GDM (being recruited to the study before week 20 of pregnancy) and the participants in the rest of the studies were diagnosed with GDM between weeks 24 and 28 of gestation. The meta-analysis showed that supplementation lowers serum glucose, insulin levels, and HOMA-IR index, but only in pregnant women with GDM. Moreover, both probiotics and synbiotics lower serum insulin level and HOMA-IR index, but the glucose lowering effect is specific only to probiotics and not synbiotics. Probiotic supplementation may improve glucose metabolism in pregnant women with GDM. There is a need for more RCT studies with larger groups to better estimate this effect.