Glycolysis in the control of blood glucose homeostasis

Guo, Xin; Li, Honggui; Xu, Huaxi; Woo, Sung Oh; Dong, Hui; Lu, Fanghong; Lange, Alex J.; Wu, Chaodong

doi:10.1016/j.apsb.2012.06.002

Cited by 125 publications

(98 citation statements)

References 98 publications

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“…Pyruvate metabolism was shown to be implicated in diabetes, as reflected by increased activity of pyruvate dehydrogenase kinase (PDK) in diabetic subjects (PDK plays significant role in glucose disposal as it decreases the activity of PDC) [42]. In general, glycolytic pathway was shown to be dysregulated in diabetes [43]. A study in rats showed, for example, that an alloxan-induced diabetic state significantly altered the activities of glycolytic enzymes in lymphocytes [44].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Selenium Supplementation on Glucose Homeostasis and the Expression of Genes Related to Glucose Metabolism

et al. 2016

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The aim of the study was to evaluate the effect of selenium supplementation on the expression of genes associated with glucose metabolism in humans, in order to explain the unclear relationship between selenium and the risk of diabetes. For gene expression analysis we used archival samples of cDNA from 76 non-diabetic subjects supplemented with selenium in the previous study. The supplementation period was six weeks and the daily dose of selenium was 200 µg (as selenium yeast). Blood for mRNA isolation was collected at four time points: before supplementation, after two and four weeks of supplementation, and after four weeks of washout. The analysis included 15 genes encoding selected proteins involved in insulin signaling and glucose metabolism. In addition, HbA1c and fasting plasma glucose were measured at three and four time points, respectively. Selenium supplementation was associated with a significantly decreased level of HbA1c but not fasting plasma glucose (FPG) and significant down-regulation of seven genes: INSR, ADIPOR1, LDHA, PDHA, PDHB, MYC, and HIF1AN. These results suggest that selenium may affect glycemic control at different levels of regulation, linked to insulin signaling, glycolysis, and pyruvate metabolism. Further research is needed to investigate mechanisms of such transcriptional regulation and its potential implication in direct metabolic effects.

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Section: Discussionmentioning

confidence: 99%

The Effect of Selenium Supplementation on Glucose Homeostasis and the Expression of Genes Related to Glucose Metabolism

et al. 2016

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“…6 E ). A possible explanation can be attributed to metabolites for de novo lipogenesis that derive from glycolysis (30), e.g., dihydroxyacetonephosphate as a precursor for the glycerol backbone of triacylglycerides (31).…”

Section: Discussionmentioning

confidence: 99%

Spare mitochondrial respiratory capacity permits human adipocytes to maintain ATP homeostasis under hypoglycemic conditions

Keuper

Jastroch

et al. 2013

FASEB j.

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Mitochondrial dysfunction in white adipose tissue plays a key role in the pathogenesis of type 2 diabetes. Emerging evidence specifically suggests that altered oxidative phosphorylation in adipocytes may have a relevant effect on systemic glucose homeostasis, requiring understanding of adipocyte bioenergetics. We analyzed energetic flux of an intact human adipocyte cell model by plate-based respirometry and extracellular acidification. During differentiation, we discovered that glycolytic ATP production was increasingly replaced by mitochondrial oxidative metabolism (from 20 to 60%). This observation was corroborated by simultaneous up-regulation of canonical mitochondrial gene programs, such as peroxisome proliferator-activated receptor γ coactivator α (PGC1α; 150-fold) and cytochrome c-1 (CytC; 3-fold). Mimicking diabetic phenotypes by exposure to various glucose levels (0, 5, and 25 mM) resulted in immediate adjustments of glycolytic and mitochondrial activity that aimed to maintain intracellular ATP. We conclude that ATP deficits by mitochondrial failure are compensated by glycolytic ATP production, resulting in inefficient conversion of glucose to cellular ATP. Metabolic inefficiency may enhance glucose uptake, therefore improving systemic glucose homeostasis. Notably, mature adipocytes developed a high spare respiratory capacity (increased by 6-fold) permitting rapid adaptation to metabolic changes. Spare respiratory capacity may also allow additional metabolic scope for energy dissipation, potentially offering new therapeutic targets for the treatment of metabolic disease.

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“…Glucose consumption is a multistage process involving a first ratelimiting step of membrane transport carried out by GLUT proteins [37,38,39,40,41], followed by metabolism mediated by enzymes of the glycolytic and downstream pathways [42,43]. The glucose analogue 2-deoxyglucose (2DG) is taken up by cells and phosphorylated to 2-deoxyglucose-6-phosphate (2DG6P) by glucokinase (GK) but is not further metabolized and accumulates inside cells proportional to its uptake.…”

Section: Discussionmentioning

confidence: 99%

A colorimetric bioassay for quantitation of both basal and insulin-induced glucose consumption in 3T3-L1 adipose cells

Diaz

Camargo

Ondo-Méndez

et al. 2020

Heliyon

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Introduction: The quantitation of glucose consumption in animal cell cultures is mainly based on the use of radiolabeled or fluorescent analogues, resulting in expensive and tedious procedures, requiring special equipment and, sometimes, with potential health and environmental risks. Objectives: The objective of this work was to evaluate the application of a blood plasma colorimetric assay to quantify glucose consumption in in vitro cultures of adipose cells. Methods: We worked with 3T3-L1 adipose cells differentiated by 7-8 days, which were exposed to different initial glucose concentrations (5.5, 2.8 and 1.4 mM) for variable times, either in the absence or the presence of 100 nM insulin. Using a commercial colorimetric glucose assay, extracellular glucose was determined, and glucose uptake was calculated as the difference between the initial and final glucose concentration. Results: The colorimetric assay allowed us to quantify glucose uptake in our cell model, observing a linear response over time (r 2 !0.9303) to the different glucose concentrations, both in the basal and insulin-induced condition. The insulin-stimulated glucose consumption was higher than basal consumption at all glucose concentrations evaluated, but significant differences were observed at 120-, 360-and 480-min in glucose 5.5 mM (p 0.01, n ¼ 5), and 240 min in glucose 1.4 mM (p 0.01, n ¼ 5). A V max of 4.1 and 5.9 nmol/ml/min (basal and insulin-induced, respectively) and a K m of 1.1 mM (same in basal vs insulin-stimulated) were calculated. The bioassay was also useful in a pharmacological context: in glucose 1.4 mM, glucose consumption showed an effect that depended on insulin concentration, with a calculated EC 50 of 18.4 AE 1.1 nM. Conclusions: A simple and low-cost bioassay is proposed to quantify glucose consumption in 3T3-L1 adipose cells.

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Glycolysis in the control of blood glucose homeostasis

Cited by 125 publications

References 98 publications

The Effect of Selenium Supplementation on Glucose Homeostasis and the Expression of Genes Related to Glucose Metabolism

The Effect of Selenium Supplementation on Glucose Homeostasis and the Expression of Genes Related to Glucose Metabolism

Spare mitochondrial respiratory capacity permits human adipocytes to maintain ATP homeostasis under hypoglycemic conditions

A colorimetric bioassay for quantitation of both basal and insulin-induced glucose consumption in 3T3-L1 adipose cells

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