Nitric oxide and vascular insulin resistance

Wu, Guoyao; Meininger, Cynthia J.

doi:10.1002/biof.3

Cited by 158 publications

(108 citation statements)

References 48 publications

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“…L-arginine availability (with the exception of zero concentration) was inversely proportional to superoxide production ( Fig. 2E) perhaps as a result of the effect of the lack of L-arginine availability on the uncoupled iNOS phenomenon (Wu & Meininger 2009). Effect of L-arginine on the phosphorylation state and protein levels of AMPK and protein levels of HSP72 in the absence or presence of a proinflammatory cytokine cocktail Since b-cell metabolism is dependent on regulation by the activity of key enzymes such as AMPK (Kiely et al 2007, Newsholme et al 2007b, protein levels of AMPK and its AMP-P were determined following 24 h incubation in various concentrations of L-arginine in the absence or presence of proinflammatory cytokines.…”

Section: Resultsmentioning

confidence: 94%

l-Arginine is essential for pancreatic β-cell functional integrity, metabolism and defense from inflammatory challenge

Krause¹,

McClenaghan²,

Flatt³

et al. 2011

Journal of Endocrinology

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In this work, our aim was to determine whether L-arginine (a known insulinotropic amino acid) can promote a shift of b-cell intermediary metabolism favoring glutathione (GSH) and glutathione disulfide (GSSG) antioxidant responses, stimulus-secretion coupling and functional integrity. Clonal BRIN-BD11 b-cells and mouse islets were cultured for 24 h at various L-arginine concentrations (0-1 . 15 mmol/l) in the absence or presence of a proinflammatory cytokine cocktail (interleukin 1b, tumour necrosis factor a and interferon g). Cells were assessed for viability, insulin secretion, GSH, GSSG, glutamate, nitric oxide (NO), superoxide, urea, lactate and for the consumption of glucose and glutamine. Protein levels of NO synthase-2, AMP-activated protein kinase (AMPK) and the heat shock protein 72 (HSP72) were also evaluated. We found that L-arginine at 1 . 15 mmol/l attenuated the loss of b-cell viability observed in the presence of proinflammatory cytokines. L-Arginine increased total cellular GSH and glutamate levels but reduced the GSSG/GSH ratio and glutamate release. The amino acid stimulated glucose consumption in the presence of cytokines while also stimulating AMPK phosphorylation and HSP72 expression. Proinflammatory cytokines reduced, by at least 50%, chronic (24 h) insulin secretion, an effect partially attenuated by L-arginine. Acute insulin secretion was robustly stimulated by L-arginine but this effect was abolished in the presence of cytokines. We conclude that L-arginine can stimulate b-cell insulin secretion, antioxidant and protective responses, enabling increased functional integrity of b-cells and islets in the presence of proinflammatory cytokines. Glucose consumption and intermediary metabolism were increased by L-arginine. These results highlight the importance of L-arginine availability for b-cells during inflammatory challenge.

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Section: Resultsmentioning

confidence: 94%

l-Arginine is essential for pancreatic β-cell functional integrity, metabolism and defense from inflammatory challenge

Krause¹,

McClenaghan²,

Flatt³

et al. 2011

Journal of Endocrinology

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“…Decreased NO function is multifactorial, involving both impaired endothelial production of NO and accelerated NO inactivation. The diminished NO synthesis associated with type 2 diabetes has been attributed to uncoupling of receptor-mediated signal transduction (Angeline et al, 2011), to a relative deficiency of L-arginine and to a decrease availability of eNOS cofactor, BH 4 (Wu and Meininger, 2009;Angeline et al, 2011). The reduced NO bioavailability is caused largely by decreased NO production, which may result from accumulation of asymmetric dimethylarginine (ADMA) or reduced bioavailability of L-arginine (Gates et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

The effect of metformin and exercise on serum lipids, nitric oxide synthase and liver nitric oxide levels in streptozotocin-nicotinamide induced diabetic rats

Akyüz¹,

Tekin²,

Aydn³

et al. 2012

Afr. J. Pharm. Pharmacol.

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The objective of this study was to determine the effects of metformin treatment and exercise intervention on lipid metabolism, nitric oxide (NO), nitric oxide synthase (NOS) and glucose levels in streptozotocin-nicotinamide (STZ-NA) induced diabetic rats. Male wistar rats were used to conduct the study and they were divided into five groups of 8 rats in each. These groups are: Control group, diabetes group (STZ-NA), diabetes and metformin (DMet) group, diabetes and exercise (DE) group, and diabetes + exercise + metformin (DEMet) group. The STZ-NA induced diabetic rats were used as a model of type 2 diabetes. Metformin was orally administered to rats. For exercise intervention, rats were forced to run in a running wheel for 10 min each day (20 m/min/day). At the end of experimental period, blood glucose, glycated hemoglobin (HbA1c) levels, plasma lecithin:cholesterol acyltransferase (LCAT) levels, serum triglyceride (TG), cholesterol, high density lipoprotein (HDL), Apo A-I, NOS and liver NO levels were determined. Metformin caused beneficial changes in blood glucose, HbA1c levels, and HDL in type 2 diabetic rats. Both administration of metformin and exercise intervention independently caused beneficial changes in blood glucose. However, the surprising result found was that exercise intervention did not optimize the result of metformin treatment. The other finding of this study was that exercise intervention increased cholesterol and NOS level but exercise combined with metformin was not better than exercise alone. Thus, it appears from the present study that metformin and exercise combination has no effect.

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“…Thus, maternal protein nutrition greatly impacts embryonic/fetal survival in pigs (Pond et al, 1969;Pond and Wu, 1981). Along with insulin-like growth factors, vascular endothelial growth factor and other growth factors, NO and polyamines are crucial for angiogenesis, embryogenesis, placental growth, uteroplacental blood flow, and transfer of nutrients from mother to fetuses, as well as fetal-placental growth and development Wu and Meininger, 2009).…”

Section: Argininementioning

confidence: 99%

Pregnancy recognition signals in mammals: the roles of interferons and estrogens

Bazer

Johnson

2017

Anim Reprod

Self Cite

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Reproduction is a highly complex biological process requiring a dialogue between the developing conceptus (embryo-fetus and associated placental membranes) and maternal uterus which must be established during the peri-implantation period for pregnancy recognition signaling and regulation of gene expression by uterine epithelial and stromal cells. The uterus provide a microenvironment in which molecules secreted by uterine epithelia or transported into the uterine lumen represent histotroph or the secretome required for growth and development of the conceptus and receptivity of the uterus to implantation by the conceptus. Pregnancy recognition signaling as related to sustaining the functional lifespan of the corpora lutea (CL) which produce progesterone; the hormone of pregnancy essential for uterine functions that support implantation and placentation required for successful outcomes of pregnancy. It is within the periimplantation period that most embryonic deaths occur in mammals due to deficiencies attributed to uterine functions or failure of the conceptus to develop appropriately, signal pregnancy recognition and/or undergo implantation and placentation. The endocrine status of the pregnant female and her nutritional status are critical for successful establishment and maintenance of pregnancy. The challenge is to understand the complexity of key mechanisms that are characteristic of successful reproduction and to use that knowledge to enhance fertility and reproductive health of animals including nonhuman primates. It is important to translate knowledge gained from studies of animals to address issues of fertility and reproductive health in humans.

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Nitric oxide and vascular insulin resistance

Cited by 158 publications

References 48 publications

l-Arginine is essential for pancreatic β-cell functional integrity, metabolism and defense from inflammatory challenge

l-Arginine is essential for pancreatic β-cell functional integrity, metabolism and defense from inflammatory challenge

The effect of metformin and exercise on serum lipids, nitric oxide synthase and liver nitric oxide levels in streptozotocin-nicotinamide induced diabetic rats

Pregnancy recognition signals in mammals: the roles of interferons and estrogens

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