Acute effect of insulin on nitric oxide synthesis in humans: a precursor-product isotopic study

Abstract

]arginine enrichments in whole blood were performed in the first 3 h in the fasting state and then following a 3-h euglycemic-hyperinsulinemic clamp (with plasma insulin raised to Ϸ1,000 pmol/l). In the last 60 min of each experimental period, at Ϸsteady-state arginine enrichment, a linear increase of 15 NOx enrichment (mean r ϭ 0.9) was detected in both experimental periods. In the fasting state, NOx FSR was 27.4 Ϯ 4.3%/ day, whereas ASR was 0.97 Ϯ 0.36 mmol/day, accounting for 0.69 Ϯ 0.27% of arginine flux. Following hyperinsulinemia, both FSR and ASR of NOx increased (FSR by Ϸ50%, to 42.4 Ϯ 6.7%/day, P Ͻ 0.005; ASR by Ϸ25%, to 1.22 Ϯ 0.41 mmol/day, P ϭ 0.002), despite a Ϸ20 -30% decrease of arginine flux and concentration. The fraction of arginine flux used for NOx synthesis was doubled, to 1.13 Ϯ 0.35% (P Ͻ 0.003). In conclusion, whole body NOx synthesis can be directly measured over a short observation time with stable isotope methods in humans. Insulin acutely stimulates NOx synthesis from arginine. arginine;15 N nitrates; precursor pool; gas chromatography-combustion-isotope ratio mass spectrometry

Nitric Oxide Synthesis Is Reduced in Subjects With Type 2 Diabetes and Nephropathy

“…Enrichments were expressed as tracer-to-tracee ratio (TTR) (23). Whole-blood NOx enrichments were determined in the supernatant of the ethanol-containing tubes as nitrobenzene derivative (24), by gas chromatography combustion-isotope ratio mass spectrometry (Delta Plus GC-C-IRMS, ThermoElectron, Bremen, Germany), as described in detail elsewhere (20). Blood NOx concentrations were determined from the ethanol supernatant (25), using a commercial assay (Nitrate/Nitrite Colorimetric Assay kit, Cayman Chemical Co., Ann Arbor, MI), after correction of blood dilution by weight differences, and accounting for blood specific weight.…”

“…Blood NOx concentrations were determined from the ethanol supernatant (25), using a commercial assay (Nitrate/Nitrite Colorimetric Assay kit, Cayman Chemical Co., Ann Arbor, MI), after correction of blood dilution by weight differences, and accounting for blood specific weight. Plasma insulin and amino acid concentrations were determined as reported in ref (20). TNF-α, IL-6, Il-8 and Il-10, and hsCRP were measured using commercial assays.…”

“…We recently developed a precursor–product, stable isotope method to measure whole-body synthesis of NO-related compounds in vivo (20). Therefore, the aim of this study was twofold: 1 ) to measure NOx production rate (both fractional and absolute), as well as the rate of arginine conversion to NOx, in type 2 diabetic patients with diabetic nephropathy and 2 ) to study the effects of acute hyperinsulinemia on these parameters.…”

A targeted metabolic protocol with D-ribose for off-pump coronary artery bypass procedures: a retrospective analysis

“…In fact intense insulin therapy to Therapeutic Advances in Cardiovascular Disease 5 (4) control hyperglycemia is becoming the standard of care in coronary artery surgery ]. Supplemental insulin offers many benefits during hyperglycemia, most significantly in enhancing the cellular uptake of glucose, as well as increasing nitric oxide production [Tessari et al 2007]. Insufficient amounts of insulin is not only reflected in sustained hyperglycemia, but can also be associated with elevated levels of pyruvate and lactate [Klein, 1942].…”

Prenatally programmed hypertension: role of maternal diabetes

“…Besides the effect of insulin on carbohydrate metabolism, this hormone presents several actions, including the modification of lipid and protein metabolism, ion and amino acid transport, cell cycle and proliferation, cell differentiation, apoptosis, and NO synthesis (52)(53)(54). In addition, insulin and other hormones, such as ANG II and norepinephrine, can influence each other (55)(56)(57).…”