Interrelaciones entre ureagénesis y gluconeogénesis hepática en rumiantes alimentados con elevado contenido de nitrógeno / Relationships between liver ureagenesis and gluconeogenesis in ruminants fed with a high nitrogen diet

Liver ureagenesis and gluconeogénesis are essential metabolic functions in ruminants. These metabolic processes are more intensive in ruminants than other mammals, especially on grazing ruminants or those supplemented with nitrogen because they absorb large amount of the ammonia produced in the rumen and only small amounts of the intestinal glucose. Diets based on the use of forages with a high content of crude protein, rapidly degradable in the rumen, or the supplementation with non-protein nitrogen, increases the ruminal production of ammonia. The excess of ammonia is absorbed and metabolized to urea by the liver. The production of large amounts of ammonia in the rumen and its subsequent absorption can exceed the liver capacity to metabolize urea causing an overcharge in the urea cycle, demanding a large amount of α-ketoglutarate and oxalacetate to produce glutamate and aspartate. Under this condition the gluconeogenic capacity of the organism is altered because these metabolites are also required in the Krebs cycle and gluconeogenesis. The relationships between liver ureagenesis and gluconeogenesis in ruminants fed a high content of nitrogen are reviewed.

Los rumiantes alimentados con forrajes de elevado contenido de proteína rápidamente degradable en el rumen o suplementados con nitrógeno no proteínico, absorben cantidades sustanciales de amonio en el rumen y muy poca glucosa en el intestino, en circunstancias que requieren mantener una adecuada capacidad ureagénica y gluconeogénesis para sostener su eficiencia productiva. En esta condición se eleva la producción de amonio ruminal, el cual se absorbe y posteriormente se metaboliza por el hígado en urea. Las elevadas concentraciones de amonio en el rumen pueden sobrepasar la capacidad hepática de sintetizar urea, lo que provoca una sobrecarga en el ciclo de la urea y demanda una excesiva cantidad de α-cetoglutarato y oxalacetato para la formación de glutamato y aspartato, metabolitos que también son requeridos en el ciclo de Krebs y en la vía gluconeogénica, alterando con ello la capacidad gluconeogénica del organismo. El trabajo recopila y analiza las interrelaciones entre la ureagénesis y gluconeogénesis hepática en rumiantes en condiciones de pastoreo con forrajes de elevado contenido de proteínas.

Glucose administration inhibits the hepatic activation of gluconeogenesis promoted by insulin-induced hypoglycemia

The activation of hepatic gluconeogenesis in male Wistar adult 6 h fasted rats during insulin-induced hypoglycemia (IIH) was previously demonstrated. In this study, the effects of intraperitoneal (ip) glucose (100 mg/kg) on the activation of liver gluconeogenesis during IIH was investigated. Thus, 6 h fasted rats that received ip regular insulin (1 U/kg) and 30 min later ip saline (Control group) or glucose (Experimental group) were compared. All the experiments were executed 60 min after insulin injection. The glycemia of Control and Experimental groups were not different (P > 0.05). To investigate gluconeogenesis, liver perfusion experiments were performed. The results demonstrated that excepting glycerol, livers from rats which received ip glucose showed lower (P < 0.05) gluconeogenesis from L-alanine, L-glutamine, L-lactate or L-alanine + L-glutamine + L-lactate + glycerol. Therefore, the absence of glucose recovery after the glucose administration was mediated, at least in part, by an inhibition of hepatic gluconeogenesis.

Em estudo recente empregando ratos Wistar com 6 h de privação alimentar demonstramos que ocorre ativação da neoglicogênese hepática durante a hipoglicemia induzida por insulina (HII). Neste estudo, os efeitos da administração intraperitoneal (ip) de glicose (100 mg/kg) sobre a ativação da neoglicogênese hepática durante a HII foi investigada. Assim, ratos com 6 h de privação alimentar que receberam insulina regular ip (1 U/kg) e 30 min depois salina (Grupo Controle) ou glicose ip (Grupo Experimental) foram comparados. Os experimentos foram executados 60 min após a injeção de insulina. A glicemia dos grupos Controle e Experimental não foi diferente (P > 0.05). Para investigar a neoglicogênese, realizouse experimentos de perfusão de fígado. Os resultados demonstraram, exceto para o glicerol, que fígados de ratos que receberam glicose ip (Grupo Experimental), apresentaram menor taxa (P < 0.05) de neoglicogênese a partir de L-alanina, Lglutamina, L-lactato ou L-alanina + L-glutamina + L-lactato + glicerol. Portanto, a ausência de recuperação da glicemia após administração de glicose foi mediada por inibição da neoglicogênese hepática.