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Prevention of acute/severe hypoglycemia-induced neuron death by lactate administration.

ABSTRACT: Hypoglycemia-induced cerebral neuropathy can occur in patients with diabetes who attempt tight control of blood glucose and may lead to cognitive dysfunction. Accumulating evidence from animal models suggests that hypoglycemia-induced neuronal death is not a simple result of glucose deprivation, but is instead the end result of a multifactorial process. In particular, the excessive activation of poly (ADP-ribose) polymerase-1 (PARP-1) consumes cytosolic nicotinamide adenine dinucleotide (NAD(+)), resulting in energy failure. In this study, we investigate whether lactate administration in the absence of cytosolic NAD(+) affords neuroprotection against hypoglycemia-induced neuronal death. Intraperitoneal injection of sodium L-lactate corrected arterial blood pH and blood lactate concentration after hypoglycemia. Lactate administered without glucose was not sufficient to promote electroencephalogram recovery from an isoelectric state during hypoglycemia. However, supplementation of glucose with lactate reduced neuronal death by ?80% in the hippocampus. Hypoglycemia-induced superoxide production and microglia activation was also substantially reduced by administration of lactate. Taken together, these results suggest an intriguing possibility: that increasing brain lactate following hypoglycemia offsets the decrease in NAD(+) due to overactivation of PARP-1 by acting as an alternative energy substrate that can effectively bypass glycolysis and be fed directly to the citric acid cycle to maintain cellular ATP levels.

SUBMITTER: Won SJ

PROVIDER: S-EPMC3367225 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Prevention of acute/severe hypoglycemia-induced neuron death by lactate administration.

Won Seok Joon SJ Jang Bong Geom BG Yoo Byung Hoon BH Sohn Min M Lee Min Woo MW Choi Bo Young BY Kim Jin Hee JH Song Hong Ki HK Suh Sang Won SW

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20120328 6

Hypoglycemia-induced cerebral neuropathy can occur in patients with diabetes who attempt tight control of blood glucose and may lead to cognitive dysfunction. Accumulating evidence from animal models suggests that hypoglycemia-induced neuronal death is not a simple result of glucose deprivation, but is instead the end result of a multifactorial process. In particular, the excessive activation of poly (ADP-ribose) polymerase-1 (PARP-1) consumes cytosolic nicotinamide adenine dinucleotide (NAD(+)) ...[more]

PMID: 22453629

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Project description:BackgroundTigecycline, the first glycylcycline-class drug, is a broad-spectrum antibiotic with activity against multi-drug resistant (MDR) organisms. We describe a case of sustained and severe hypoglycemia in a patient treated with tigecycline for pneumonia due to MDR Klebsiella pneumoniae.Case presentationA 74-year-old man was admitted for treatment of pneumonia. At admission he had prediabetes. In the hospital he developed renal failure. On day 3, the patient experienced severe shortness of breath. He was intubated and transferred to the intensive care unit (ICU) for ventilator support. In the ICU the antibiotic regimen was cefoperazone and sulbactam (1 g every 12 h). Continuous Renal Replacement Therapy was started on that day. Test for anti-neutrophil cytoplasmic antibodies (ANCA) was positive, and so the nephrologist and rheumatologist agreed on a diagnosis of ANCA-associated vasculitis, with renal and pulmonary involvement and acute renal failure. Plasmapheresis, and high-dose methylprednisolone treatment were started on day 6, and there was obvious improvement in the patient's condition. The steroid regimen was gradually tapered to oral prednisone (35 mg every day) on day 19. Afterwards, the patient's pneumonia worsened. Sputum culture showed Klebsiella pneumoniae sensitive to only tigecycline. Tigecycline treatment (100 mg every 12 h) was administered on day 20. Hypoglycemia started about 37 h after the first dose of tigecycline. Infusion of 50% glucose through the femoral vein was required for over 20 h to maintain normal blood glucose concentrations. Tigecycline was stopped, but the hypoglycemia resolved only after a further 34 h. The insulin and C-peptide levels were found to be markedly elevated during the hypoglycemia. The Naranjo scale score of 7 indicated that the likelihood of tigecycline causing severe hypoglycemia was "probable."ConclusionThis is the first report of sustained severe hypoglycemia due to tigecycline. Oversecretion of insulin appears to have been the cause of the hypoglycemia in our patient. The mechanism needs to be investigated.

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Prevention of acute/severe hypoglycemia-induced neuron death by lactate administration.

Publications

Prevention of acute/severe hypoglycemia-induced neuron death by lactate administration.

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