Distribution of 3H-labelled 6-aminonicotinamide and accumulation of 6-Phosphogluconate in the spinal cord

G, Meyer-Estorf; Schulze, P.; Herken, H.

doi:10.1007/bf00501195

Cited by 9 publications

(2 citation statements)

References 11 publications

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“…In addition, the results of the metabolite analysis indicate metabolism of glucose through the PPP even under low glucose conditions. The origination of the PPP metabolites from glucose metabolism, especially gluconic acid, which has been seldom reported in mammalian cells [14,15], was demonstrated by [ 13 C 6 ]glucose tracer experiments (ESM Figs 1-4).…”

Section: Resultsmentioning

confidence: 84%

Identification of an intracellular metabolic signature impairing beta cell function in the rat beta cell line INS-1E and human islets

et al. 2011

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Aims/hypothesis Chronic hyperglycaemia promotes the progressive failure of pancreatic beta cells in patients with type 2 diabetes mellitus, a clinically highly relevant phenomenon known as glucotoxicity. The intracellular metabolic consequences of a chronically high availability of glucose in beta cells are, as yet, poorly understood in its full complexity. Methods An unbiased metabolite profiling analysis (GCtime-of-flight-MS) was used to identify the time course of core metabolite patterns in rat beta cell line INS-1E during exposure to high glucose concentrations and its relation to insulin expression. Results We report here that pentose phosphate pathway (PPP) metabolites accumulate remarkably during chronic but not acute glucose treatment, indicating altered processing of glucose through the pentose phosphate pathway. Subsequent functional studies in INS-1E cells and human islets revealed that a disturbance in this pathway contributes to decreases in insulin gene expression and a lack of glucose-stimulated insulin secretion. These effects were found to depend on the activation of extracellular-regulatedkinase (ERK1/2). Long-term inhibition of 6-phosphogluconic acid dehydrogenase resulted in accumulation of PPP metabolites, induced ERK1/2 activation independently of high glucose and impaired beta cell function. In turn, inhibition of ERK1/2 overstimulation during chronic glucose exposure partly inhibited metabolite accumulation and restored beta cell function. Conclusions/interpretation Based on unbiased metabolite analyses, the data presented here provide novel targets, namely the inhibition of PPP metabolite accumulation

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Section: Resultsmentioning

confidence: 84%

Identification of an intracellular metabolic signature impairing beta cell function in the rat beta cell line INS-1E and human islets

et al. 2011

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“…The analogue 6-AN exchanges with nicotinamide through the microsomal enzyme, NAD(P)-glycohydrolase, to form an ineffective product that is very slowly eliminated [31]. It appears also that NADP rather than NAD is chiefly implicated in the subsequent toxic effects [ 151, accounting for the striking d n i t y of this analogue for 6-phosphogluconate dehydrogenase rather than other dehydrogenases [29].…”

Section: -Aminonicotiiamide Toxicitymentioning

confidence: 99%

Selective vulnerability in acute energy deprivation syndromes

1993

Neuropathology Appl Neurobio

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The topography and cellular events in the experimental lesions caused by chlorosugars, 6-aminonicotinamide, dinitrobenzene and tribromoimidazole in animals are considered in relation to those features in human acute thiamine deficiency (Wernicke's) encephalopathy and for comparison in Leigh's disease. The topography and cellular changes when closely examined are different and particular to each condition, although there is a basic cellular process common to all. The pathogenesis of each condition must be considered as multifactorial and a search for the factors responsible for the neuronal and cellular selective vulnerability of different regions of the neuraxis will lead us to understanding the pathogenesis of the disease process in each instance. The experimental models offer much for the understanding of the human conditions, particularly in the search for satisfactory therapeutic strategies.

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Niacin-Nicotinamide Deficiency

Kauffman

1985

Cerebral Energy Metabolism and Metabolic Encephalopathy

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Distribution of 3H-labelled 6-aminonicotinamide and accumulation of 6-Phosphogluconate in the spinal cord

Cited by 9 publications

References 11 publications

Identification of an intracellular metabolic signature impairing beta cell function in the rat beta cell line INS-1E and human islets

Identification of an intracellular metabolic signature impairing beta cell function in the rat beta cell line INS-1E and human islets

Selective vulnerability in acute energy deprivation syndromes

Niacin-Nicotinamide Deficiency

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