scholarly journals Roles of Pyruvate, NADH, and Mitochondrial Complex I in Redox Balance and Imbalance inβCell Function and Dysfunction

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Xiaoting Luo ◽  
Rongrong Li ◽  
Liang-Jun Yan
Keyword(s):  
Insulin Secretion ◽  
Metabolic Pathways ◽  
Complex I ◽  
Redox Balance ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Glucose Levels ◽  
Cell Dysfunction ◽  
Chronic Hyperglycemia ◽  
Nadh Ubiquinone Oxidoreductase

Pancreaticβcells not only use glucose as an energy source, but also sense blood glucose levels for insulin secretion. While pyruvate and NADH metabolic pathways are known to be involved in regulating insulin secretion in response to glucose stimulation, the roles of many other components along the metabolic pathways remain poorly understood. Such is the case for mitochondrial complex I (NADH/ubiquinone oxidoreductase). It is known that normal complex I function is absolutely required for episodic insulin secretion after a meal, but the role of complex I inβcells in the diabetic pancreas remains to be investigated. In this paper, we review the roles of pyruvate, NADH, and complex I in insulin secretion and hypothesize that complex I plays a crucial role in the pathogenesis ofβcell dysfunction in the diabetic pancreas. This hypothesis is based on the establishment that chronic hyperglycemia overloads complex I with NADH leading to enhanced complex I production of reactive oxygen species. As nearly all metabolic pathways are impaired in diabetes, understanding how complex I in theβcells copes with elevated levels of NADH in the diabetic pancreas may provide potential therapeutic strategies for diabetes.

Dynamic Function of the Alkyl Spacer of Acetogenins in Their Inhibitory Action with Mitochondrial Complex I (NADH-Ubiquinone Oxidoreductase)†

Biochemistry ◽  
2005 ◽  
Vol 44 (45) ◽  
pp. 14898-14906 ◽  
Author(s):  
Masato Abe ◽  
Masatoshi Murai ◽  
Naoya Ichimaru ◽  
Atsushi Kenmochi ◽  
Takehiko Yoshida ◽  
...  
Keyword(s):  
Complex I ◽  
Inhibitory Action ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Ubiquinone Oxidoreductase ◽  
Nadh Ubiquinone Oxidoreductase ◽  
Dynamic Function

Incorporation of NADH-ubiquinone Oxidoreductase (Mitochondrial Complex I) into Lipid Nanodiscs

2012 ◽  
Vol 18 (S2) ◽  
pp. 88-89
Author(s):  
D.J. Fowler ◽  
T. Ruiz ◽  
M. Radermacher ◽  
S.G. Sligar ◽  
V. Zickermann ◽  
...  
Keyword(s):  
Complex I ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Ubiquinone Oxidoreductase ◽  
Nadh Ubiquinone Oxidoreductase ◽  
Lipid Nanodiscs

Extended abstract of a paper presented at Microscopy and Microanalysis 2012 in Phoenix, Arizona, USA, July 29 – August 2, 2012.

scholarly journals DJ-1 deficiency causes metabolic abnormality in ornidazole-induced asthenozoospermia

Reproduction ◽  
2020 ◽  
Vol 160 (6) ◽  
pp. 931-941
Author(s):  
Yi Sun ◽  
Xinping Sun ◽  
Lianming Zhao ◽  
Zhe Zhang ◽  
Yupeng Wang ◽  
...  
Keyword(s):  
Small Molecules ◽  
Metabolic Pathways ◽  
Complex I ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Mitochondrial Energy Metabolism ◽  
Human Male ◽  
Purine Pathway ◽  
Lipid Metabolites ◽  
Induced Changes

Asthenozoospermia (AS), defined as low-motility spermatozoa in the ejaculate, is a frequent cause of human male infertility. DJ-1 (also known as PARK7), a protein highly associated with male sterility, binds to the mitochondrial complex I subunit to protect mitochondrial function. However, its involvement in spermatogenesis has not been fully elucidated. Previously, the levels of DJ-1 were shown to be significantly decreased in testicular tissues of rats with ornidazole (ORN)-induced AS. Here, we used a rat model to investigate the localization and expression levels of DJ-1 and its interacting NDUFS3 and NDUFA4 mitochondrial complex I subunits, as well as AS-induced metabolic alterations in testicular tissues. ORN significantly reduced the levels of DJ-1 in the nucleus of secondary spermatocytes, while increasing the expression of NDUFS3 in the cytoplasm of primary spermatocytes. Further, NDUFA4 showed higher expression after treatment with ORN. The principal ORN-induced changes in metabolic small molecules related to the accumulation of glucose, glutamine, and N-acetyl aspartate, enhancement of purine pathway, increase of the phosphatidic acid (PA) (18:0/18:1), phosphatidylethanolamine (PE) (16:0/18:1), and PA (18:0/20:4) lipid metabolites, and imbalance in the concentrations of Na+ and K+. However, we did not observe any abnormalities of certain small metabolic molecules and metal ions in semen samples from patients with AS. In conclusion, these results suggest that DJ-1 deficiency in testicular tissues might be closely related to the localization of NDUFS3 and content of NDUFA4, thus causing abnormalities in the mitochondrial energy metabolism and multiple other metabolic pathways.

Effect of lowering postprandial hyperglycemia on insulin secretion in older people with impaired glucose tolerance

2004 ◽  
Vol 287 (5) ◽  
pp. E906-E911 ◽  
Author(s):  
Annette M. Chang ◽  
Marla J. Smith ◽  
Cathie J. Bloem ◽  
Andrzej T. Galecki ◽  
Jeffrey B. Halter
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Older People ◽  
Postprandial Glucose ◽  
Tolerance Test ◽  
Β Cell ◽  
Intravenous Glucose ◽  
Glucose Levels ◽  
Cell Dysfunction ◽  
Chronic Hyperglycemia

Glucose tolerance declines with age, resulting in a high prevalence of diabetes and impaired glucose tolerance (IGT) in the older population. Hyperglycemia per se can lead to impaired β-cell function (glucose toxicity). We tested the role of glucose toxicity in age-related β-cell dysfunction in older people (65 ± 8 yr) with IGT treated with the α-glucosidase inhibitor acarbose ( n = 14) or placebo ( n = 13) for 6 wk in a randomized, double-blind study. Baseline and posttreatment studies included 1) an oral glucose tolerance test (OGTT), 2) 1-h postprandial glucose monitoring, 3) a frequently sampled intravenous glucose tolerance test (insulin sensitivity, or SI), and 4) glucose ramp clamp (insulin secretion rates, or ISR), in which a variable glucose infusion increases plasma glucose from 5 to 10 mM. The treatment groups had similar baseline body mass index; fasting, 2-h OGTT, and 1-h postprandial glucose levels; and SI. In these carefully matched older people with IGT, both fasting (5.7 ± 0.2 vs. 6.3 ± 0.2 mM, P = 0.002) and 1-h postprandial glucose levels (6.9 ± 0.3 vs. 8.2 ± 0.4 mM, P = 0.02) were significantly lower in the acarbose than in the placebo group. Despite this reduction of chronic hyperglycemia in the acarbose vs. placebo group, measures of insulin secretion (ISR area under the curve: 728 ± 55 vs. 835 ± 81 pmol/kg, P = 0.9) and acute insulin response to intravenous glucose (329 ± 67 vs. 301 ± 54 pM, P = 0.4) remained unchanged and impaired. Thus short-term improvement of chronic hyperglycemia does not reverse β-cell dysfunction in older people with IGT.

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