The effects of dietary nitrate on plasma glucose and insulin sensitivity in sheep

Abstract

Nitrate (NO3¯) is an effective non‐protein nitrogen source for gut microbes and reduces enteric methane (CH4) production in ruminants. Nitrate is reduced to ammonia by rumen bacteria with nitrite (NO2¯) produced as an intermediate. The absorption of NO2¯ can cause methaemoglobinaemia in ruminants. Metabolism of NO3¯ and NO2¯ in blood and animal tissues forms nitric oxide (NO) which has profound physiological effects in ruminants and has been shown to increase glucose uptake and insulin secretion in rodents and humans. We hypothesized that absorption of small quantities of NO2¯ resulting from a low‐risk dose of dietary NO3¯ will increase insulin sensitivity (SI) and glucose uptake in sheep. We evaluated the effect of feeding sheep with a diet supplemented with 18 g NO3¯/kg DM or urea (Ur) isonitrogenously to NO3¯, on insulin and glucose dynamics. A glucose tolerance test using an intravenous bolus of 1 ml/kg LW of 24% (w/v) glucose was conducted in twenty sheep, with 10 sheep receiving 1.8% supplementary NO3¯ and 10 receiving supplementary urea isonitrogenously to NO3¯. The MINMOD model used plasma glucose and insulin concentrations to estimate basal plasma insulin (Ib) and basal glucose concentration (Gb), insulin sensitivity (SI), glucose effectiveness (SG), acute insulin response (AIRg) and disposition index (DI). Nitrate supplementation had no effect on Ib (p > .05). The decrease in blood glucose occurred at the same rate in both dietary treatments (SG; p = .60), and there was no effect of NO3¯ on either Gb, SI, AIRg or DI. This experiment found that the insulin dynamics assessed using the MINMOD model were not affected by NO3¯ administered to fasted sheep at a low dose of 1.8% NO3¯ in the diet.

Caloric Restriction (CR) Plus High-Nitrate Beetroot Juice Does Not Amplify CR-Induced Metabolic Adaptation and Improves Vascular and Cognitive Functions in Overweight Adults: A 14-Day Pilot Randomised Trial

“…This study corroborates these positive effects, but it also shows the potential existence of a synergy between the two interventions as an almost statistically significant greater drop in systolic BP was observed in the CR + BRJ group, which also exhibited greater improvements in endothelial function (average flux and NO-dependent endothelial activity). The vascular effects could be explained by the enhancement of endothelial function mediated by various mechanisms, such as (i) increased NO production through SIRT1/AMPK/Akt-eNOS-NO pathway [ 32 , 56 , 57 , 58 , 59 ] and nitrate-nitrite-NO pathway via dietary nitrate [ 33 , 34 , 35 ], (ii) greater insulin sensitivity [ 22 , 59 , 60 , 61 , 62 , 63 , 64 ], (iii) upregulation of antioxidants defenses [ 27 , 28 , 29 , 30 , 59 , 65 , 66 , 67 ] and reduced ROS generation via increased mitochondrial efficiency.…”

Changes in hematological, biochemical, and blood gases parameters in response to progressive inclusion of nitrate in the diet of Holstein calves

“…This mechanism in ruminants is well documented and has been attributed either to a lower release of pancreatic insulin [29] or to increased glucose production in the liver [30]. However, some authors hypothesized the beneficial effects of using NO 3 ̄ and NO 2 ̄ as precursors of nitric oxide, at blood and tissue level, on glucose uptake and increased insulin sensitivity in humans and rats [31,32], but not confirmed yet in ruminants [33].…”

Dietary Betaine Impacts Metabolic Responses to Moderate Heat Exposure in Sheep

“…Results from the IVGTT were subjected to Bergman's minimal modeling [39,40], using MINMOD Millennium (2001) [41]. The MINMOD Millennium (referred to as MINMOD from here on) computer model estimation has been validated for use in humans, rats, pigs, dogs, and cats [42], and although data suggests that this model may be a useful tool in the assessment of insulin sensitivity in cows [37,43,44], dairy goats [45], and sheep [46], it has not been validated for use in these species. This model is used to describe the nature of the interactions between glucose and insulin actions and kinetics.…”