Intrinsic regulation of glucose output by rat liver

Glinsmann, Walter H.; Hern, EP; Lynch, Almorris

doi:10.1152/ajplegacy.1969.216.4.698

Cited by 94 publications

(52 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present findings in primate fetal liver are analogous to those previously observed with isolated fetal rat liver explants in culture (9). We therefore speculate that direct (glucose concentration-dependent) regulation of glycogen synthetase activity and glycogen synthesis, present in adult mammalian liver (5,7,16,(18)(19)(20), is not developed during early neonatal life. This may contribute to the low plasma glucose removal rates after bolus glucose injection observed at this time (2,4,15,20,30).…”

Section: Discussionsupporting

confidence: 89%

Glucose Regulation by Isolated Near Term Fetal Monkey Liver

et al. 1975

View full text Add to dashboard Cite

ExtractNear term fetal monkey livers were perfused with a closed recirculating system and a defined perfusion medium. Livers from normal fetal animals were able to release glucose rapidly into the perfusate when they were exposed to glucagon, cyclic AMP, or an aglycemic perfusate, but they did not remove glucose rapidly from the perfusate, synthesize glycogen, or activate liver glycogen synthetase in response to hyperglycemia (Figs. 1,2, and 3; Table I ). Insulin decreased glucose mobilization in response to aglycemia, but did not stimulate glucose uptake during hyperglycemia; insulin activated glycogen synthetase (Table 1; Figs. 1 and 3). Livers from fetuses of streptozotocin-treated mothers and livers from 2-week-old neonates released more glucose into the perfusate in response to aglycemia then did livers from normal fetal monkeys (Fig. 4). These observations support the possibility that neonatal monkey liver is capable of rapidly mobilizing glucose during periods of hypoglycemia but is unable to take up glucose and store glycogen rapidly during periods of hyperglycernia. SpeculationIncomplete development of glycogen synthetic mechanisms in early postnatal life may contribute to decreased liver glycogen reserves. These decreased reserves may then be inadequate for maintaining normoglycemia during periods of increased glucose uptake or utilization by peripheral tissue. (9,10,27,29) support the possibility that at birth hormonal regulation of glycogen metabolism is competent, but direct glucose regulation of glycogen synthesis has not developed.In humans, development of rapid glucose and glycogen mobilizing responses precedes birth (1, 13, 26), and liver glycogen levels, high at birth, decline rapidly during the first few hours of life (3,28). Idiopathic neonatal hypoglycemia does not appear to be associated with impaired glycogenolytic mechanisms since it usually occurs when liver glycogen stores are depleted (3, 28). Consequently, we considered that incomplete development of glycogen synthetic mechanisms in early postnatal life might contribute to decreased liver glycogen reserves and that these inadequate reserves are incapable of maintaining normoglycemia.We now provide additional support for this possibility based on studies with isolated perfused rhesus monkey livers from near term fetuses of normal mothers and mothers with streptozotocin-induced glucose intolerance, and from normal monkey neonates. In all three groups, hepatic glucose removal rates were low in the presence of high glucose concentrations in the perfusion solution. Changes in circulating glucose concentration did not modify glycogen synthetase activity, but in all instances liver glucose was released in response to hypoglycemia. Direct effects of exogenous glucagon and insulin on hepatic glucose output and glycogen cycle enzyme activity were demonstrated in the near term fetus group. METHODS ANIMALSOne of the primary functions for liver is to maintain blood glucose levels. This is achieved by changes in gluconeogenic Pregnant Macaca mulatt...

show abstract

Section: Discussionsupporting

confidence: 89%

Glucose Regulation by Isolated Near Term Fetal Monkey Liver

et al. 1975

View full text Add to dashboard Cite

show abstract

“…A2). Immediately after, glucose begins to return toward basal levels due to glucose's own effect to enhance cellular uptake (due to mass action as well as glucose transporter mobilization to the membrane) (37) and glucose's ability to suppress hepatic glucose output ("autoregulation") (23,24). We termed these two latter effects of glucose per se "glucose effectiveness" (16).…”

Section: Branch #1: Clinical Tools and The Disposition Indexmentioning

confidence: 99%

“…• Prandial elevation in glycemia is renormalized in part by glucose's ability to enhance its own disposal and suppress liver production (16,(23)(24)(25) independent of the plasma insulin response. This "glucose effectiveness" is reduced in type 2 diabetes (26).…”

mentioning

confidence: 99%

Orchestration of Glucose Homeostasis

Bergman

2007

Diabetes

View full text Add to dashboard Cite

“…When glycogen stores are present, an increase in the rate of glycogenolysis may be the preferred autoregulatory response to hypoglycemia. Livers from fed rats responded to a perfusion without glucose by releasing glucose and lactate into the perfusate, and the loss of tissue glycogen could account for all of the carbon released as glucose and lactate (3).…”

Section: Mechanisms Involved In Hypoglycemic Autoregulationmentioning

confidence: 99%

Autoregulation of hepatic glucose production

Moore

Connolly

Cherrington

1998

European Journal of Endocrinology

104

View full text Add to dashboard Cite

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 dif®cult 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 signi®cant 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 (#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. European Journal of Endocrinology 138 240±248

show abstract

Intrinsic regulation of glucose output by rat liver

Cited by 94 publications

References 0 publications

Glucose Regulation by Isolated Near Term Fetal Monkey Liver

Glucose Regulation by Isolated Near Term Fetal Monkey Liver

Orchestration of Glucose Homeostasis

Autoregulation of hepatic glucose production

Contact Info

Product

Resources

About