Browsing by Subject "lactate"

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  • Similä, Minna E.; Auranen, Mari; Piirilä, Päivi Liisa (2020)
    Background: A deficiency of muscle phosphofructokinase (PFKM) causes a rare metabolic muscle disease, the Tarui disease (Glycogen storage disease type VII, GSD VII) characterized by exercise intolerance with myalgia due to an inability to use glucose as an energy resource. No medical treatment for GSD VII currently exists. The aim of this study was to determine whether a dietary intervention with excessive fat intake would benefit GSD VII.Patient and Methods: A ketogenic diet (KD) intervention implemented as a modified Atkins diet was established for one patient with PFKM deficiency, with a low late lactate response and very high ammonia levels associated with exercise. We recorded the KD intervention for a total of 5 years with clinical and physiotherapeutic evaluations and regular laboratory parameters. Cardiopulmonary exercise testing, including breath gas analysis and venous lactate and ammonia measurements, was performed before KD and at 3, 8 months and 5 years after initiation of KD.Results: During the 5 years on KD, the patient's muscle symptoms had alleviated and exercise tolerance had improved. In exercise testing, venous ammonia had normalized, the lactate profile remained similar, but oxygen uptake and mechanical efficiency had increased and parameters showing ventilation had improved.Conclusions: This study is the first to show a long-term effect of KD in GSD VII with an alleviation of muscle symptoms, beneficial effects on breathing, and improvement in exercise performance and oxygen uptake. Based on these findings, KD can be recommended under medical and nutritional supervision for selected patients with GSD VII, although further research of this rare disease is warranted.
  • Zetterman, Teemu; Markkula, Ritva; Kalso, Eija (2021)
    Objectives: Fibromyalgia (FM) patients have an increased risk for glucose metabolism disturbances, and impaired glucose tolerance may be associated with symptom severity. Elevated levels of plasma lactate have been detected in FM patients. Both pyruvate and lactate are produced in glucose metabolism and reflect oxidative metabolism. The objective of our study was to analyse disturbances in glucose, pyruvate, or lactate metabolism in FM patients. Methods: We measured plasma levels of glucose, pyruvate, and lactate during an oral glucose tolerance test in 40 non-diabetic, female FM patients and 30 age- and gender-matched healthy controls. Results: FM patients showed a higher glycaemic response to the glucose load at 1 hour (F [1,68] = 10.4, P = .006) and 2 hours (F [1,68] = 7.80, P = .02), and higher glucose area under the curve (13.8 [SD 2.92] vs 11.6 [SD 2.31], P < .01), than healthy controls. Group differences were explained by higher body mass index and percentage of smokers among the FM patients. Pyruvate and lactate levels were similar in both groups. Discussion: Impaired glucose regulation in FM patients is likely not due to FM itself, but to associated lifestyle factors. Our results highlight the importance of assessing the glucose regulation status and the lifestyle factors affecting glucose regulation in FM patients for prevention or early treatment of diabetes and associated complications.
  • Erkkilä, K.; Aito, H.; Aalto, K.; Pentikäinen, V.; Dunkel, L. (2002)
    Dysregulation of male germ cell apoptosis has been associated with the pathogenesis of male infertility. Therefore, factors involved in the regulation of germ cell death are being actively investigated. Here, we studied the effects of lactate on human male germ cell death, using as a model a testis tissue culture in which physiological contacts are maintained between the germ cells and the supportive somatic Sertoli cells. Apoptosis of spermatocytes, spermatids and a few spermatogonia was induced by culturing segments of seminiferous tubules under serum-free conditions. This germ cell death was inhibited effectively and dose-dependently by lactate, indicating that it plays a crucial role in controlling cell death cascades of male germ cells. Interestingly, the anti-apoptotic role of lactate was not associated with changes in testicular adenine nucleotide (ATP, ADP and AMP) levels. In the seminiferous tubules, the final site of the death-suppressing action of lactate appeared to be downstream along the cell death pathway activated by the Fas receptor of the germ cells. In conclusion, testicular cell death was effectively regulated by lactate, which may be regarded as a potential compound for optimizing in-vitro methods involving male germ cells for assisted reproduction.
  • Calza, Giulio; Nyberg, Elisabeth; Mäkinen, Matias; Soliymani, Rabah; Cascone, Annunziata; Lindholm, Dan; Barborini, Emanuele; Baumann, Marc; Lalowski, Maciej; Eriksson, Ove (2018)
    Metformin is the first line drug for type 2 diabetes but its molecular mechanisms remain unclear. Here, we have studied the acute effect of a therapeutically relevant intrahepatic concentration of metformin on glucose production from lactate. We selected the perfused rat liver as experimental system since it enables the complete control of drug dosage. We used MALDI (matrix-assisted laser desorption/ionization) mass spectrometry imaging to estimate the concentration of metformin in the livers and we measured the concentration of glucose in the effluent medium under basal conditions and following lactate addition. MALDI mass spectra of thin-sections of freeze-clamped rat liver perfused with metformin showed a peak at 130.16 m/z which was unambiguously assigned to metformin. The mass spectrometric detection limit was at a tissue concentration of about 250 nM, and uptake of metformin from the perfusion medium to the liver occurred with a K-m of 0.44 mM. Metformin was evenly distributed in the liver irrespective of its concentration in the perfusion medium and the duration of a perfusion. At a parenchymal concentration of 30 mu M, metformin did not induce any significant suppression of the basal or lactate-induced glucose release from the liver. These results show that matrix-assisted laser desorption/ionization mass spectrometry imaging can be applied to estimate the tissue concentration and distribution of metformin in a therapeutically relevant micromolar concentration range. Our findings challenge the view that metformin causes an inhibition of glucose release from the liver by an acute inhibition of mitochondrial glycerol 3-phosphate dehydrogenase (EC
  • Krššák, Martin; Lindeboom, Lucas; Schrauwen-Hinderling, Vera; Szczepaniak, Lidia S.; Derave, Wim; Lundbom, Jesper; Befroy, Douglas; Schick, Fritz; Machann, Jürgen; Kreis, Roland; Boesch, Chris (2021)
    H-1-MR spectroscopy of skeletal muscle provides insight into metabolism that is not available noninvasively by other methods. The recommendations given in this article are intended to guide those who have basic experience in general MRS to the special application of H-1-MRS in skeletal muscle. The highly organized structure of skeletal muscle leads to effects that change spectral features far beyond simple peak heights, depending on the type and orientation of the muscle. Specific recommendations are given for the acquisition of three particular metabolites (intramyocellular lipids, carnosine and acetylcarnitine) and for preconditioning of experiments and instructions to study volunteers.
  • Walker, Hannah K.; Ottka, Claudia; Lohi, Hannes; Handel, Ian; Clements, Dylan N.; Gow, Adam G.; Mellanby, Richard J. (2022)
    Background Metabolic profiling identifies seasonal variance of serum metabolites in humans. Despite the presence of seasonal disease patterns, no studies have assessed whether serum metabolites vary seasonally in dogs. Hypothesis There is seasonal variation in the serum metabolite profiles of healthy dogs. Animals Eighteen healthy, client-owned dogs. Methods A prospective cohort study. Serum metabolomic profiles were assessed monthly in 18 healthy dogs over a 12-month period. Metabolic profiling was conducted using a canine-specific proton nuclear magnetic resonance spectroscopy platform, and the effects of seasonality were studied for 98 metabolites using a cosinor model. Seasonal component was calculated, which describes the seasonal variation of each metabolite. Results We found no evidence of seasonal variation in 93 of 98 metabolites. Six metabolites had statistically significant seasonal variance, including cholesterol (mean 249 mg/dL [6.47 mmol/L] with a seasonal component amplitude of 9 mg/dL [0.23 mmol/L]; 95% confidence interval [CI] 6-13 mg/dL [0.14-0.33 mmol/L], P < .008), with a peak concentration of 264 mg/dL (6.83 mmol/L) in June and trough concentration of 236 mg/dL (6.12 mmol/L) in December. In contrast, there was a significantly lower concentration of lactate (mean 20 mg/dL [2.27 mmol/L] with a seasonal component amplitude of 4 mg/dL [0.42 mmol/L]; 95% CI 2-6 mg/dL [0.22-0.62 mmol/L], P < .001) during the summer months compared to the winter months, with a peak concentration of 26 mg/dL (2.9 mmol/L) in February and trough concentration of 14 mg/dL (1.57 mmol/L) in July. Conclusions and Clinical Importance We found no clear evidence that seasonal reference ranges need to be established for serum metabolites of dogs.
  • Piirilä, Päivi; Similä, Minna E.; Palmio, Johanna; Wuorimaa, Tomi; Ylikallio, Emil; Sandell, Satu; Haapalahti , Petri; Uotila, Lasse; Tyynismaa, Henna; Udd, Bjarne; Auranen, Mari (2016)
    Introduction: Glycogen storage disease V (GSDV, McArdle disease) and GSDVII (Tarui disease) are the most common of the rare disorders of glycogen metabolism. Both are associated with low lactate levels on exercise. Our aim was to find out whether lactate response associated with exercise testing could distinguish between these disorders. Methods: Two siblings with Tarui disease, two patients with McArdle disease and eight healthy controls were tested on spiroergometric exercise tests with follow-up of venous lactate and ammonia. Results: A late increase of lactate about three times the basal level was seen 10-30 min after exercise in patients with Tarui disease being higher than in McArdle disease and lower than in the controls. Ammonia was increased in Tarui disease. Discussion: Our results suggest that follow-up of lactate associated with exercise testing can be utilized in diagnostics to distinguish between different GSD diseases.
  • Viitala, Emma Wilhelmiina (Helsingin yliopisto, 2022)
    The gastrointestinal (GI) epithelium is composed of a single layer of cells with a turnover time of only a few days. Due to its location at the barrier between GI tract contents and the underlaying mucosa, the epithelium is constantly exposed to stress such as toxic agents and a variety of pathogens and susceptible to injury. Accordingly, the homeostatic growth as well as repair of injury in epithelium must be efficient and strictly regulated. Misregulated repair of the injured epithelium can lead to pathologies such as chronic inflammation or cancer. Underlying stromal cells such as fibroblasts provide growth factors and other signaling molecules regulating the epithelial cell stemness, differentiation and repair, but the stromal regulatory pathways during regeneration are poorly understood. The aim of this study was to establish a consensus view on the heterogeneity of GI fibroblasts, as well as to map potential epithelium derived signals affecting fibroblast function in homeostatic and injury situations using literature review, in silico approaches, and murine primary intestinal fibroblast culture. Seurat and CellChat R packages were used to perform integration and interaction analyses of six previously published mouse and three human single- cell RNA-sequencing datasets of colonic epithelial and mesenchymal cells isolated in homeostatic and/or inflammatory conditions. Murine primary intestinal fibroblasts were treated with identified potential signaling factors ex vivo and 3’RNAseq was performed to identify transcriptional responses. Both mesenchymal and epithelial cell clusters were identified in the scRNAseq data. Interestingly, similar fibroblast populations could be found in the murine and human data. I identified several epithelium-derived signaling molecules potentially targeting GI fibroblasts and focused on Gas6-Axl pathway and lactate. I confirmed high and specific expression of the Gas6 receptor Axl in intestinal fibroblasts, but recombinant Gas6 failed to induce significant changes in cultured primary fibroblasts. Lactate-treated primary intestinal fibroblasts reprogrammed their transcriptome with main alterations in metabolic pathways and induction of neutrophil-attracting chemokines. In this work I suggest a consensus model for GI fibroblast subpopulations and suggest epithelium derived lactate as a powerful means to reprogram fibroblasts.