THE EFFECT OF L-LEUCINE ON HEPATIC GLUCOSE FORMATION

A direct inhibitory effect of leucine on hepatic glucose output has been suggested by previous observations in our laboratory. However, it has not been possible to separate the action of leucine from that of insulin. The current studies were undertaken in order to determine the effect of leucine on hepatic glucose formation in vitro, in the absence of insulin. In liver slices from fasted mice, leucine was shown to inhibit the incorporation of C14 from various C14-labeled precursors into glucose. These results are consistent with the postulate that leucine inhibits the rate of gluconeogenesis, and thus hepatic glucose output, independent of insulin. Accordingly, the effect of leucine on production of hypoglycemia cannot be regarded as a specific cause of hypoglycemia in certain infants. Assuming that the action of leucine is similar in all individuals, the induction of hypoglycemia by leucine in some individuals must reflect underlying defects in the intracellular regulation of the complex, multi-enzyme pathway of gluconeogenesis. Clarification of the mechanism of action of leucine on gluconeogenesis should contribute to current understanding of the means by which hepatic glucose output is regulated.

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Autoregulation of hepatic glucose production

Acta Endocrinologica ◽

10.1530/eje.0.1380240 ◽

1998 ◽

pp. 240-248 ◽

Cited By ~ 77

Author(s):

MC Moore ◽

CC Connolly ◽

AD Cherrington

Keyword(s):

Hepatic Glucose Production ◽

Glucose Production ◽

Hepatic Glycogen ◽

Neural Pathways ◽

Hepatic Glucose Output ◽

Counterregulatory Hormones ◽

Hepatic Glucose ◽

Glucose Output

In vitro evidence indicates that the liver responds directly to changes in circulating glucose concentrations with reciprocal changes in glucose production and that this autoregulation plays a role in maintenance of normoglycemia. Under in vivo conditions it is difficult to separate the effects of glucose on neural regulation mediated by the central nervous system from its direct effect on the liver. Nevertheless, it is clear that nonhormonal mechanisms can cause significant changes in net hepatic glucose balance. In response to hyperglycemia, net hepatic glucose output can be decreased by as much as 60-90% by nonhormonal mechanisms. Under conditions in which hepatic glycogen stores are high (i.e. the overnight-fasted state), a decrease in the glycogenolytic rate and an increase in the rate of glucose cycling within the liver appear to be the explanation for the decrease in hepatic glucose output seen in response to hyperglycemia. During more prolonged fasting, when glycogen levels are reduced, a decrease in gluconeogenesis may occur as a part of the nonhormonal response to hyperglycemia. A substantial role for hepatic autoregulation in the response to insulin-induced hypoglycemia is most clearly evident in severe hypoglycemia (< or = 2.8 mmol/l). The nonhormonal response to hypoglycemia apparently involves enhancement of both gluconeogenesis and glycogenolysis and is capable of supplying enough glucose to meet at least half of the requirement of the brain. The nonhormonal response can include neural signaling, as well as autoregulation. However, even in the absence of the ability to secrete counterregulatory hormones (glucocorticoids, catecholamines, and glucagon), dogs with denervated livers (to interrupt neural pathways between the liver and brain) were able to respond to hypoglycemia with increases in net hepatic glucose output. Thus, even though the endocrine system provides the primary response to changes in glycemia, autoregulation plays an important adjunctive role.

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Histidine Promotes the Glucose Synthesis through Activation of the Gluconeogenic Pathway in Bovine Hepatocytes

Animals ◽

10.3390/ani11113295 ◽

2021 ◽

Vol 11 (11) ◽

pp. 3295

Author(s):

Tianyu Yang ◽

Zhiqiang Cheng ◽

Maocheng Jiang ◽

Xiaoyu Ma ◽

Osmond Datsomor ◽

...

Keyword(s):

Mrna Level ◽

Regulatory Effect ◽

Hepatic Glucose Output ◽

Grass Silage ◽

Lactating Cows ◽

Hepatic Glucose ◽

Glucose Synthesis ◽

Limiting Amino Acid ◽

Glucose Output

Histidine (His) is considered to be the first-limiting amino acid (AA) on grass silage-based diets in lactation cows, which correlate positively with lactose yield. The higher glucose requirements of lactating cows can be met through a combination of increased capacity for gluconeogenesis and increased supply of gluconeogenic precursors. However, the effect of His on the expression of gluconeogenic genes in the bovine hepatocytes is less known. Therefore, this study aimed to investigate the regulatory effect of His on the key gluconeogenic genes and glucose output in bovine hepatocytes. The addition of 0.15, 0.6, and 1.2 mM His in a medium significantly enhanced (p < 0.05) the viability of bovine hepatocytes. Remarkably, 1.2 mM His induced profound changes (p < 0.05) in the mRNA level of key genes involved in gluconeogenesis, including PCK1, PCK2, FBP1, and G6PC in vitro. Furthermore, the mRNA expression of PCK1 was significantly elevated (p < 0.05) by the addition of 1.2 mM His at 3, 6, 12, and 24 h of incubation. The hepatic glucose output increased (p < 0.05) linearly with increasing His concentration. These findings indicate that the addition of His may be efficiently converted into glucose via the upregulation of genes related to the gluconeogenic pathway.

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