Lactate, a Neglected Factor for Diabetes and Cancer Interaction

Wu, Yong; Dong, Yunzhou; Atefi, Mohammad; Liu, Yanjun; Elshimali, Yahya; Vadgama, Jaydutt V.

doi:10.1155/2016/6456018

Cited by 82 publications

(81 citation statements)

References 152 publications

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“…Lactate is a classical marker for the diagnosis of primary mitochondrial diseases, but also a sign of upregulated glycolytic metabolism. Interestingly, T2DM patients also show increased levels of plasmatic lactate [45,46], con rming both the rise of glycolytic metabolism and the metabolic co-morbidity between both diseases.…”

Section: Discussionmentioning

confidence: 91%

Disrupted Mitochondrial and Metabolic Plasticity Underlie Comorbidity Between Age-related and Degenerative Disorders as Parkinson Disease and Type 2 Diabetes Mellitus

Juárez‐Flores

Ezquerra

Gonzàlez-Casacuberta

et al. 2020

Preprint

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Background. Idiopathic Parkinson’s disease (iPD) and Type 2 Diabetes Mellitus (T2DM) are chronic, degenerative, multisystemic and age-related diseases, with eventual epidemiological co-morbidity and potential overlap in molecular basis. This study aims to explore if metabolic and mitochondrial alterations underlie the suggested epidemiologic and clinical co-morbidity at molecular level. Methods. To evaluate the adaptation of iPD to a simulated pre-diabetogenic state, we exposed primary cultured fibroblasts from iPD patients and controls to standard (5mM) and high (25mM) glucose concentrations to further characterize metabolic and mitochondrial resilience.Results. iPD fibroblasts showed increased levels of organic and amino acid levels related to mitochondrial metabolism with respect to controls, and these differences were enhanced in high glucose conditions (citric, suberic and sebacic acids levels increased, as well as alanine, glutamate, aspartate, arginine and ornithine amino acids; p-values between 0.001 and p=0.05). The accumulation of metabolites in iPD fibroblasts was associated (and probably due) to the concomitant mitochondrial dysfunction observed at enzymatic, oxidative, respiratory and morphologic level. Metabolic and mitochondrial plasticity of controls was not observed in iPD fibroblasts, that were unable to adapt to different glucose conditions. Impaired metabolism and mitochondrial activity in iPD may limit energy supply for cell survival. Moreover, deficient plasticity to adapt to disrupted glucose balance characteristic of T2DM may underlay the comorbidity between both diseases. Conclusions:Fibroblasts form iPD patients showed mitochondrial impairment resulting in the accumulation of organic and amino acids related to mitochondrial metabolism, especially when exposed to high glucose condition. Mitochondrial and metabolic defects down warding cell plasticity to adapt to changing glucose bioavailability may explain the comorbidity between iPD and T2DM.

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Section: Discussionmentioning

confidence: 91%

Disrupted Mitochondrial and Metabolic Plasticity Underlie Comorbidity Between Age-related and Degenerative Disorders as Parkinson Disease and Type 2 Diabetes Mellitus

Juárez‐Flores

Ezquerra

Gonzàlez-Casacuberta

et al. 2020

Preprint

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“…Non-oxidative insulin-dependent utilization of glucose is typically enhanced in patients with T2DM and GDM. Growing interconversion of lactate and pyruvate is greatly increased and upregulates CNDP1 which is necessary for carnosine uptake [55,56]. The inhibited fatty acid oxidation concatenated by the hypoxia condition inducing hypoxia-inducible factor-1 (HIF-1) which triggers glycolysis in T2DM and GDM patients [57].…”

Section: Discussionmentioning

confidence: 99%

“…Hence, the increased plasma lactate may improve the responsiveness to insulin and promote its secretion. Meanwhile, lactate concentrations are chronically increased in diabetic patients with obesity when hyperlactatemia in obese individuals was found to be preceding the diabetes onset process [56].…”

Section: Discussionmentioning

confidence: 99%

Association of Proteins Modulating Immune Response and Insulin Clearance during Gestation with Antenatal Complications in Patients with Gestational or Type 2 Diabetes Mellitus

Kopylov

Kaysheva

Папышева

et al. 2020

Cells

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Background: The purpose of the study is to establish and quantitatively assess protein markers and their combination in association with insulin uptake that may be have value for early prospective recognition of diabetic fetopathy (DF) as a complication in patients with diabetes mellitus during gestation. Methods: Proteomic surveying and accurate quantitative measurement of selected proteins from plasma samples collected from the patients with gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) who gave birth of either healthy or affected by maternal diabetes newborns was performed using mass spectrometry. Results: We determined and quantitatively measured several proteins, including CRP, CEACAM1, CNDP1 and Ig-family that were significantly differed in patients that gave birth of newborns with signs of DF. We found that patients with newborns associated with DF are characterized by significantly decreased CEACAM1 (113.18 ± 16.23 ng/mL and 81.09 ± 10.54 ng/mL in GDM and T2DM, p < 0.005) in contrast to control group (515.6 ± 72.14 ng/mL, p < 0.005). On the contrary, the concentration of CNDP1 was increased in DF-associated groups and attained 49.3 ± 5.18 ng/mL and 37.7 ± 3.34 ng/mL (p < 0.005) in GDM and T2DM groups, respectively. Among other proteins, dramatically decreased concentration of IgG4 and IgA2 subclasses of immunoglobulins were noticed. Conclusion: The combination of the measured markers may assist (AUC = 0.893 (CI 95%, 0.785-0.980) in establishing the clinical finding of the developing DF especially in patients with GDM who are at the highest risk of chronic insulin resistance.Cells 2020, 9, 1032 2 of 22 mellitus, type 2 diabetes mellitus (T2DM) or gestational diabetes mellitus (GDM) suffered by pregnant women. Diabetic fetopathy is the cause of premature birth, chronic hypoxia, respiratory depression, asphyxia of the fetus at birth, accompanied by various metabolic disorders, and can also be the cause of newborns death [1][2][3]. This is one of the most common forms of obstetric complications and perinatal losses evoked from hyperglycemia manifested in a disturbance of glucose tolerance and occurred or was first recognized during pregnancy [4]. It is also possible that the disturbance of carbohydrate metabolism could precede pregnancy but has not been previously detected [5,6]. During pregnancy, hyperglycemia is induced by a gradually increased insulin resistance due to both placental hormones and the mother's hormones (prolactin, estrogen and cortisol). The growing concentration of these hormones is compensated by a decrease in the clearance of endogenously produced insulin [2,5].According to the WHO data for 2016, up to 25% of pregnant women are at risk of hyperglycemia during pregnancy [7]. An overwhelming majority (from 75% to 90%) of elevated blood glucose levels during pregnancy emerges from the already progressing GDM [8,9]. Statistics of the IDF for 2017 demonstrate up to 204 million women aged between 20 to 79 years live with different types of diabetes, while up to 21.3 m...

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“…Cancer cells commonly cause a localized acidosis that prevents the entry of CQ. 214 Hence, CQ can affect metastatic cells in transition and this can explain the statistically significant effect of CQ against metastatic cancer cells in patients. 213 Such a niche results from interactions between tumor and stromal cells.…”

Section: Cq Effects On Cancer Stem Cellsmentioning

confidence: 99%

“…213 Such a niche results from interactions between tumor and stromal cells. 214 Hence, CQ can affect metastatic cells in transition and this can explain the statistically significant effect of CQ against metastatic cancer cells in patients. 215 Furthermore, metastatic cells are preferentially vulnerable to lysosomal inhibition.…”

Section: Cq Effects On Cancer Stem Cellsmentioning

confidence: 99%

Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways

2019

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Chloroquines are 4-aminoquinoline-based drugs mainly used to treat malaria. At pharmacological concentrations, they have significant effects on tissue homeostasis, targeting diverse signaling pathways in mammalian cells. A key target pathway is autophagy, which regulates macromolecule turnover in the cell. In addition to affecting cellular metabolism and bioenergetic flow equilibrium, autophagy plays a pivotal role at the interface between inflammation and cancer progression. Chloroquines consequently have critical effects in tissue metabolic activity and importantly, in key functions of the immune system. In this article, we will review the work addressing the role of chloroquines in the homeostasis of mammalian tissue, and the potential strengths and weaknesses concerning their use in cancer therapy.

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Lactate, a Neglected Factor for Diabetes and Cancer Interaction

Cited by 82 publications

References 152 publications

Disrupted Mitochondrial and Metabolic Plasticity Underlie Comorbidity Between Age-related and Degenerative Disorders as Parkinson Disease and Type 2 Diabetes Mellitus

Disrupted Mitochondrial and Metabolic Plasticity Underlie Comorbidity Between Age-related and Degenerative Disorders as Parkinson Disease and Type 2 Diabetes Mellitus

Association of Proteins Modulating Immune Response and Insulin Clearance during Gestation with Antenatal Complications in Patients with Gestational or Type 2 Diabetes Mellitus

Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways

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