Glucagon-mediated impairments in hepatic and peripheral tissue nutrient disposal are not aggravated by increased lipid availability

Chen, Sheng-Song; Santomango, Tammy S.; Williams, Phillip E.; Lacy, D. Brooks; McGuinness, Owen P.

doi:10.1152/ajpendo.90821.2008

Cited by 5 publications

(5 citation statements)

References 35 publications

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“…NEFA is the major fuel oxidized by the liver and can modulate the suppression of glucose production by insulin. Our recent work indicates NEFAs interact with glucagon to impair NHGU during TPN[21]. In the present study, NEFA uptake and fractional extraction by the liver were increased, despite only modest changes in circulating NEFA concentrations.…”

Section: Discussionsupporting

confidence: 49%

“…Infusion catheters were placed in the splenic vein for insulin and/or glucagon administration and in the inferior vena cava (IVC) for delivery of nutritional support. Flow probes (Transonic Systems, Ithaca, NY) were placed in the left common iliac vein with the tip positioned distal to the anastomosis with the IVC and in the abdominal aorta via the right external iliac artery [19, 21]. …”

Section: Methodsmentioning

confidence: 99%

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Continuous low-dose fructose infusion does not reverse glucagon-mediated decrease in hepatic glucose utilization

et al. 2011

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Objective An adaptation to chronic total parenteral nutrition (TPN; 75% of non protein calories as glucose) is the liver becomes a major consumer of glucose with lactate release as a by-product. The liver is able to further increase liver glucose uptake when a small dose of fructose is acutely infused via the portal system. Glucagon, commonly elevated during inflammatory stress, is a potent inhibitor of glucose uptake by the liver during TPN. The aim was to determine if chronic fructose infusion could overcome the glucagon-mediated decrease in hepatic glucose uptake. Material/methods Studies were performed in conscious insulin-treated chronically catheterized pancreatectomized dogs that adapted to TPN for 33 h. They were then assigned to one of 4 groups: TPN (C), TPN + fructose (4.4 μmol·kg−1·min−1, F), TPN+ glucagon (0.2 pmol·kg−1·min−1, GGN), or a TPN + fructose and glucagon (F+GGN) for an additional 63h (33–96h). Insulin, fructose and glucagon were infused into the portal vein. During that period all animals received a fixed insulin infusion 0.4mU· kg−1·min−1 (33–96h) and the glucose infusion rates were adjusted to maintain euglycemia (6.6 mM). Results Chronic fructose infusion was unable to further enhance net hepatic glucose uptake (NHGU; μmol·kg−1·min−1) (31.1±2.8 vs. 36.1±5.0; C vs. F) nor was it able to overcome glucagon-mediated decrease in NHGU (10.0±4.4 vs. 12.2±3.9; GGN vs. F+GGN). Conclusion In summary, chronic fructose infusion cannot augment liver glucose uptake during TPN nor can it overcome the inhibitory effects of glucagon.

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Section: Discussionsupporting

confidence: 49%

Section: Methodsmentioning

confidence: 99%

Continuous low-dose fructose infusion does not reverse glucagon-mediated decrease in hepatic glucose utilization

et al. 2011

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“…Thus, the earliest studies reported quite high activity of hepatic GK, about 45 mU/mg protein in the fasted state. However, more recent studies do not agree with these results, and situate the GK activity in two different ranges: either about 10 mU/mg protein ( 126 ) or 10–15 μU/mg protein ( 135 ) . While these differences are probably related to the experimental conditions rather than to the activity assessing method, further studies should be developed in order to better characterise this enzyme in the dog.…”

Section: Glucokinase In Mammalsmentioning

confidence: 85%

Nutritional regulation of glucokinase: a cross-species story

Panserat

Rideau²,

Polakof

2014

Nutr. Res. Rev.

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The glucokinase (GK) enzyme (EC 2.7.1.1.) is essential for the use of dietary glucose because it is the first enzyme to phosphorylate glucose in excess in different key tissues such as the pancreas and liver. The objective of the present review is not to fully describe the biochemical characteristics and the genetics of this enzyme but to detail its nutritional regulation in different vertebrates from fish to human. Indeed, the present review will describe the existence of the GK enzyme in different animal species that have naturally different levels of carbohydrate in their diets. Thus, some studies have been performed to analyse the nutritional regulation of the GK enzyme in humans and rodents (having high levels of dietary carbohydrates in their diets), in the chicken (moderate level of carbohydrates in its diet) and rainbow trout (no carbohydrate intake in its diet). All these data illustrate the nutritional importance of the GK enzyme irrespective of feeding habits, even in animals known to poorly use dietary carbohydrates (carnivorous species).

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“…Chronic administration of TPN augments the liver's capacity to take up glucose and metabolize it to lactate [31,35], however infection [36] and even very small increases in glucagon during stress [37] can have profound long‐term effects on the liver, lowering its ability to dispose of carbohydrate during TPN. In addition, it has been suggested that glucagon can chronically impair insulin stimulated muscle glucose disposal during nutritional support, probably via an indirect mechanism [38]. Thus, hyperglycemia, aggravated by both infection and glucagon, is a common complication of TPN administration [31].…”

Section: Glucagon's Effect During Injury or Infectionmentioning

confidence: 99%

Physiologic action of glucagon on liver glucose metabolism

Ramnanan

Edgerton

Kraft

et al. 2011

Diabetes Obesity Metabolism

233

183

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Glucagon is a primary regulator of hepatic glucose production (HGP) in vivo during fasting, exercise and hypoglycaemia. Glucagon also plays a role in limiting hepatic glucose uptake and producing the hyperglycaemic phenotype associated with insulin deficiency and insulin resistance. In response to a physiological rise in glucagon, HGP is rapidly stimulated. This increase in HGP is entirely attributable to an enhancement of glycogenolysis, with little to no acute effect on gluconeogenesis. This dramatic rise in glycogenolysis in response to hyperglucagonemia wanes with time. A component of this waning effect is known to be independent of hyperglycemia, though the molecular basis for this tachyphylaxis is not fully understood. In the overnight fasted state, the presence of basal glucagon secretion is essential in countering the suppressive effects of basal insulin, resulting in the maintenance of appropriate levels of glycogenolysis, fasting HGP and blood glucose. The enhancement of glycogenolysis in response to elevated glucagon is critical in the life-preserving counterregulatory response to hypoglycaemia, as well as a key factor in providing adequate circulating glucose for working muscle during exercise. Finally, glucagon has a key role in promoting the catabolic consequences associated with states of deficient insulin action, which supports the therapeutic potential in developing glucagon receptor antagonists or inhibitors of glucagon secretion.

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Glucagon-mediated impairments in hepatic and peripheral tissue nutrient disposal are not aggravated by increased lipid availability

Cited by 5 publications

References 35 publications

Continuous low-dose fructose infusion does not reverse glucagon-mediated decrease in hepatic glucose utilization

Continuous low-dose fructose infusion does not reverse glucagon-mediated decrease in hepatic glucose utilization

Nutritional regulation of glucokinase: a cross-species story

Physiologic action of glucagon on liver glucose metabolism

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