Low pH of interstitial fluid around hippocampus of the brain in diabetic OLETF rats

  • Yoshinori Marunaka
  • Kanji Yoshimoto
  • Wataru Aoi
  • Shigekuni Hosogi
  • Hiroshi Ikegaya
Keywords: pH, Hippocampus, Diabetes mellitus, OLETF rat, Antimony pH electrode

Abstract

Background

We have reported that pH values of ascites and interstitial fluids around the liver in Otsuka Long-Evans Tokushima Fatty (OLETF) rats are significantly lower than normal pH, 7.40, of mammalian body fluids (Biochem Biophys Res Commun 2013, 432:650), and that this lowered pH of interstitial fluid causes the insulin resistance in diabetic patients by decreasing insulin-binding to its receptors (J Physiol Sci 2013, 63:S199). In the preset study, we tried to measure the interstitial fluid pH in diabetic OLETF rats, since the interstitial fluid pH plays key factors in the brain function from a viewpoint of the binding affinity of neurotransmitters to their receptors.

Findings

We found that the pH value of interstitial fluids around hippocampus, the most important area for memory, in diabetic OLETF rats was lower than that in normal rats by measuring pH with antimony pH electrodes.

Conclusions

The lowered pH of interstitial fluid around hippocampus of the brain in diabetic rats observed in the present study suggests that the function of hippocampus of the brain would be diminished due to low affinity of various types of neurotransmitters, playing key roles in the hippocampus function, to their receptors. Therefore, we indicate that maintenance of the interstitial fluid pH at the normal level would be one of the most important key factors for molecular and cellular therapies in various types of diseases including diabetes mellitus.

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References

Aoi W, Hosogi S, Niisato N, Yokoyama N, Hayata H, Miyazaki H, Kusuzaki K, Fukuda T, Fukui M, Nakamura N, Marunaka Y: Improvement of insulin resistance, blood pressure and interstitial pH in early developmental stage of insulin resistance in OLETF rats by intake of propolis extracts. Biochem Biophys Res Commun. 2013, 432: 650-653. 10.1016/j.bbrc.2013.02.029. http://www.ncbi.nlm.nih.gov/pubmed/23416075, http://www.sciencedirect.com/science/article/pii/S0006291X13002751

CrossRefPubMedGoogle Scholar

Hayata H, Miyazaki H, Niisato N, Yokoyama N, Marunaka Y: Involvement of the extracellular pH in skeletal muscle insulin resistance. [Abstract]. J Physiol Sci. 2013, 63: S199-

Google Scholar

Cederholm J, Wibell L: Glucose intolerance in middle-aged subjects-a cause of hypertension?. Acta Med Scand. 1985, 217: 363-371.http://www.ncbi.nlm.nih.gov/pubmed/4013827,

CrossRefPubMedGoogle Scholar

Eriksson KF, Lindgarde F: Contribution of estimated insulin resistance and glucose intolerance to essential hypertension. [Abstract]. J Int Med. 1991, 229: 75-83.http://www.ncbi.nlm.nih.gov/pubmed/2043225,

Google Scholar

Bao W, Srinivasan S, Berenson G: Persistent elevation of plasma insulin levels is associated with increased cardiovascular risk in children and young adults. Circulation. 1996, 93: 54-59. 10.1161/01.CIR.93.1.54. http://www.ncbi.nlm.nih.gov/pubmed/8616941, http://circ.ahajournals.org/content/93/1/54

CrossRefPubMedGoogle Scholar

Haffner S, Ferrannini E, Hazuda H, Stern M: Clustering of cardiovascular risk factors in confirmed prehypertensive individuals. Hypertension. 1992, 20: 38-45. 10.1161/01.HYP.20.1.38. http://www.ncbi.nlm.nih.gov/pubmed/1618551, http://hyper.ahajournals.org/content/20/1/38.full.pdf

CrossRefPubMedGoogle Scholar

Marunaka Y, Aoi W, Hosogi S, Niisato N, Yokoyama N, Hayata H, Miyazaki H, Kusuzaki K, Taruno A, Nomura T: What is the role of interstitial pH in diabetes mellitus? Improving action of propolis on type II diabetes mellitus via pH regulation. [Abstract]. Int J Mol Med. 2013, 32: S50-

Google Scholar

Chheda NN, Seybt MW, Schade RR, Postma GN: Normal values for pharyngeal pH monitoring. Ann Otol Rhinol Laryngol. 2009, 118: 166-171. http://www.ncbi.nlm.nih.gov/pubmed/19374146, http://www.annals.com/toc/auto_abstract.php?id=15355

CrossRefPubMedGoogle Scholar

Yoshimoto K, Watanabe Y, Tanaka M, Kimura M: Serotonin2C receptors in the nucleus accumbens are involved in enhanced alcohol-drinking behavior. Eur J Neurosci. 2012, 35: 1368-1380. 10.1111/j.1460-9568.2012.08037.x. http://www.ncbi.nlm.nih.gov/pubmed/22512261, http://onlinelibrary.wiley.com/doi/10.1111/j.1460-9568.2012.08037.x/full

PubMedCentralCrossRefPubMedGoogle Scholar

Hosogi S, Miyazaki H, Nakajima K, Ashihara E, Niisato N, Kusuzaki K, Marunaka Y: An inhibitor of Na+/H+ exchanger (NHE), ethyl-isopropyl amiloride (EIPA), diminishes proliferation of MKN28 human gastric cancer cells by decreasing the cytosolic Cl- concentration via DIDS-sensitive pathways. Cell Physiol Biochem. 2012, 30: 1241-1253. 10.1159/000343315. http://www.ncbi.nlm.nih.gov/pubmed/23075671, http://www.karger.com/Article/Pdf/343315

CrossRefPubMedGoogle Scholar

Kitagawa M, Niisato N, Shiozaki A, Ohta-Fujimoto M, Hosogi S, Miyazaki H, Ichikawa D, Otsuji E, Marunaka Y: A regulatory role of K+-Cl- cotransporter in the cell cycle progression of breast cancer MDA-MB-231 cells. Arch Biochem Biophys. 2013, 539: 92-98. 10.1016/j.abb.2013.06.014. http://www.ncbi.nlm.nih.gov/pubmed/23831333, http://www.sciencedirect.com/science/article/pii/S0003986113001847

CrossRefPubMedGoogle Scholar

Marunaka Y, Niisato N, Taruno A, Ohta M, Miyazaki H, Hosogi S, Nakajima K, Kusuzaki K, Ashihara E, Nishio K, Iwasaki Y, Nakahari T, Kubota T: Regulation of epithelial sodium transport via epithelial Na+ channel. J Biomed Biotechnol. 2011, 2011: 978196-http://www.ncbi.nlm.nih.gov/pubmed/22028593, http://www.hindawi.com/journals/bmri/2011/978196/

PubMedCentralCrossRefPubMedGoogle Scholar

Nagao H, Nakajima K, Niisato N, Hirota R, Bando H, Sakaguchi H, Hisa Y, Marunaka Y: K+-Cl- cotransporter 1 (KCC1) negatively regulates NGF-induced neurite outgrowth in PC12 cells. Cell Physiol Biochem. 2012, 30: 538-551. 10.1159/000341436. http://www.ncbi.nlm.nih.gov/pubmed/22813581, http://www.karger.com/Article/Pdf/341436

CrossRefPubMedGoogle Scholar

Nakajima K, Niisato N, Marunaka Y: Quercetin stimulates NGF-induced neurite outgrowth in PC12 cells via activation of Na+/K+/2Cl- cotransporter. Cell Physiol Biochem. 2011, 28: 147-156. 10.1159/000331723. http://www.ncbi.nlm.nih.gov/pubmed/21865857, http://www.karger.com/Article/Pdf/331723

CrossRefPubMedGoogle Scholar

Nakajima K, Niisato N, Marunaka Y: Enhancement of tubulin polymerization by Cl--induced blockade of intrinsic GTPase. Biochem Biophys Res Commun. 2012, 425: 225-229. 10.1016/j.bbrc.2012.07.072. http://www.ncbi.nlm.nih.gov/pubmed/22828510, http://www.sciencedirect.com/science/article/pii/S0006291X1201368X

CrossRefPubMedGoogle Scholar

Niisato N, Ohta M, Eaton DC, Marunaka Y: Hypotonic stress upregulates beta- and gamma-ENaC expression through suppression of ERK by inducing MKP-1. Am J Physiol Renal Physiol. 2012, 303: F240-252. 10.1152/ajprenal.00198.2011. http://www.ncbi.nlm.nih.gov/pubmed/22573375, http://ajprenal.physiology.org/content/ajprenal/303/2/F240.full.pdf

PubMedCentralCrossRefPubMedGoogle Scholar

Kitagawa M, Niisato N, Hosogi S, Shiozaki A, Otsuji E, Marunaka Y: A role of K+-Cl- cotransporter in the cell cycle regulation of breast cancer MDA-MB-231 cells. [Abstract]. J Physiol Sci. 2013, 63: S137-

Google Scholar

Hosogi S, Miyazaki H, Kusuzaki K, Niisato N, Marunaka Y: Cl- channels/transporters as new targets for cancer therapies based on disruption of autophagy ability via modification of lysosome acidification. [Abstract]. J Physiol Sci. 2013, 63: S139-

Google Scholar

Hosogi S, Ohta M, Nakajima K, Ashihara E, Niisato N, Marunaka Y: The mechanisms of Na+/H+ exchanger inhibitor on proliferation of gastric cancer cells with several pathways. [Abstract]. J Physiol Sci. 2012, 62: S138-

Google Scholar

Toledo FG, Goodpaster BH: The role of weight loss and exercise in correcting skeletal muscle mitochondrial abnormalities in obesity, diabetes and aging. Mol Cell Endocrinol. 2013, 379: 30-34. 10.1016/j.mce.2013.06.018. http://www.ncbi.nlm.nih.gov/pubmed/23792186, http://www.sciencedirect.com/science/article/pii/S0303720713002566

CrossRefPubMedGoogle Scholar

Flittiger B, Klapperstuck M, Schmalzing G, Markwardt F: Effects of protons on macroscopic and single-channel currents mediated by the human P2X7 receptor. Biochim Biophys Acta. 2010, 1798: 947-957. 10.1016/j.bbamem.2010.01.023. http://www.ncbi.nlm.nih.gov/pubmed/20138022, http://ac.els-cdn.com/S0005273610000404/1-s2.0-S0005273610000404-main.pdf?_tid=0120225a-4d85-11e3-a4ad-00000aacb362&acdnat=1384472119_ef1888bdc18e3e174f2a7aa64d7b6bb0

CrossRefPubMedGoogle Scholar

Zalyapin EA, Bouley R, Hasler U, Vilardaga JP, Lin HY, Brown D, Ausiello DA: Effects of the renal medullary pH and ionic environment on vasopressin binding and signaling. Kidney Int. 2008, 74: 1557-1567. 10.1038/ki.2008.412. http://www.ncbi.nlm.nih.gov/pubmed/18813286, http://www.nature.com/ki/journal/v74/n12/pdf/ki2008412a.pdf

PubMedCentralCrossRefPubMedGoogle Scholar

Mirza Z, Kamal MA, Abuzenadah AM, Al-Qahtani MH, Karim S: Establishing genomic/transcriptomic links between Alzheimer’s disease and type II diabetes mellitus by meta-analysis approach. CNS Neurol Disord Drug Targets. 2013, (in press). http://www.ncbi.nlm.nih.gov/pubmed/24059308

Google Scholar

Packard MG, Goodman J: Factors that influence the relative use of multiple memory systems. Hippocampus. 2013, 23: 1044-1052. 10.1002/hipo.22178. http://www.ncbi.nlm.nih.gov/pubmed/23929809, http://onlinelibrary.wiley.com/doi/10.1002/hipo.22178/pdf

CrossRefPubMedGoogle Scholar

Published
2019-01-31
Section
Review