Time course of the hepatic adaptation to TPN: interaction with glycogen depletion

Chen, Sheng-Song; Torres-Sanchez, Carlos J.; Hosein, Nadeen; Zhang, Yiqun; Lacy, D. Brooks; McGuinness, Owen P.

doi:10.1152/ajpendo.00192.2004

Cited by 9 publications

(9 citation statements)

References 27 publications

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“…The liver transitions from a site of modest glucose uptake and storage to an organ that efficiently converts glucose to lactate (9,10). This adaptation shifts the role of the liver from a site of glycogen synthesis to a major site of lactate production.…”

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confidence: 99%

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

Chen

Santomango²,

Williams³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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Glucose, fat, and glucagon availability are increased in diabetes. The normal response of the liver to chronic increases in glucose availability is to adapt to become a marked consumer of glucose. Yet this fails to occur in diabetes. The aim was to determine whether increased glucagon and lipid interact to impair the adaptation to increased glucose availability. Chronically catheterized well controlled depancreatized conscious dogs (n = 21) received 3 days of continuous parenteral nutrition (TPN) that was either high in glucose [C; 75% nonprotein calories (NPC)] or in lipid (HL; 75% NPC) in the presence or absence of a low dose (one-third basal) chronic intraportal infusion of glucagon (GN; 0.25 ng.kg(-1).min(-1)). During the 3 days of TPN, all groups received the same insulin algorithm; the total amount of glucose infused (GIR) was varied to maintain isoglycemia ( approximately 120 mg/dl). On day 3 of TPN, hepatic metabolism was assessed. Glucose and insulin levels were similar in all groups. GIR was decreased in HL and C + GN ( approximately 30%) and was further decreased in HL + GN (55%). Net hepatic glucose uptake was decreased approximately 15% in C + GN, and HL and was decreased approximately 50% in HL + GN. Lipid alone or combined with glucagon decreased glucose uptake by peripheral tissues. Despite impairing whole body glucose utilization, HL did not limit whole body energy disposal. In contrast, glucagon suppressed whole body energy disposal irrespective of the diet composition. In summary, failure to appropriately suppress glucagon secretion adds to the dietary fat-induced impairment in both hepatic and peripheral glucose disposal. In addition, unlike increasing the percentage of calories as fat, inappropriate glucagon secretion in the absence of compensatory hyperinsulinemia limits whole body nutrient disposition.

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confidence: 99%

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

Chen

Santomango²,

Williams³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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“…Even more surprisingly, substantial liver glucose uptake occurred in the absence of hyperglycemia (ϳ6.7 mmol/l) and in only mild hyperinsulinemia (102 pmol/l) (1). Recently, our group (3) observed that the enhancement in the capacity of the liver to take up glucose (i.e., adaptive response) begins within 5 h after initiation of TPN and is nearly fully manifest by 24 h.…”

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confidence: 99%

Route-dependent effect of nutritional support on liver glucose uptake

Chen¹,

Torres-Sanchez²,

Hosein³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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The liver is a major site of glucose disposal during chronic (5 day) total parenteral (TPN) and enteral (TEN) nutrition. Net hepatic glucose uptake (NHGU) is dependent on the route of delivery when only glucose is delivered acutely; however, the hepatic response to chronic TPN and TEN is very similar. We aimed to determine whether the route of nutrient delivery altered the acute (first 8 h) response of the liver and whether chronic enteral delivery of glucose alone could augment the adaptive response to TPN. Chronically catheterized conscious dogs received either TPN or TEN containing glucose, Intralipid, and Travasol for either 8 h or 5 days. Another group received TPN for 5 days, but ϳ50% of the glucose in the nutrition was given via the enteral route (TPNϩEG). Hepatic metabolism was assessed with tracer and arteriovenous difference techniques. In the presence of similar arterial plasma glucose levels (ϳ6 mM), NHGU and net hepatic lactate release increased approximately twofold between 8 h and 5 days in TPN and TEN. NHGU (26 Ϯ 1 vs. 23 Ϯ 3 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) and net hepatic lactate release (44 Ϯ 1 vs. 34 Ϯ 6 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) in TPNϩEG were similar to results for TPN, despite lower insulin levels (96 Ϯ 6 vs. 58 Ϯ 16 pM, TPN vs. TPNϩEG). TEN does not acutely enhance NHGU or disposition above that seen with TPN. However, partial delivery of enteral glucose is effective in decreasing the insulin requirement during chronic TPN.intestine; glycogen IN STRESSED STATES (trauma, injury, or infection) nutritional support is often provided to patients either via the parenteral (TPN) or enteral (TEN) route. Prior studies suggest that when the nutrition (either TPN or TEN) is given continuously for 5 days liver glucose uptake is markedly augmented; the liver removes ϳ45% of the exogenous glucose (1). Even more surprisingly, substantial liver glucose uptake occurred in the absence of hyperglycemia (ϳ6.7 mmol/l) and in only mild hyperinsulinemia (102 pmol/l) (1). Recently, our group (3) observed that the enhancement in the capacity of the liver to take up glucose (i.e., adaptive response) begins within 5 h after initiation of TPN and is nearly fully manifest by 24 h.The enteral route is the preferred route for delivery of exogenous nutrients (12,14). In postsurgical and stressed patients, isocaloric enteral nutrition can be given without significant accompanying hyperglycemia (22, 23) compared with that shown with TPN. A potential benefit of the enteral route is that when only glucose is delivered via the enteral route in the acute setting it enhances net hepatic glucose uptake (NHGU) to a greater extent than when glucose is delivered via a peripheral route; this route-dependent effect has been termed the "portal signal" (7,20). The portal signal can rapidly (Ͻ15 min) augment NHGU; it does not require the presence of hyperglycemia or hyperinsulinemia (11). Surprisingly, when TEN is administered chronically in unstressed animals, which should activate the portal signal, NHGU is not any greater than that seen with TPN...

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“…AMPK was not activated by ND-4 in our study. Moreover, in our prior work, hepatic glycogen content did not alter the hepatic adaptation to nutrient delivery [15].…”

Section: Discussionmentioning

confidence: 45%

Liver, but Not Muscle, Has an Entrainable Metabolic Memory

et al. 2014

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Hyperglycemia in the hospitalized setting is common, especially in patients that receive nutritional support either continuously or intermittently. As the liver and muscle are the major sites of glucose disposal, we hypothesized their metabolic adaptations are sensitive to the pattern of nutrient delivery. Chronically catheterized, well-controlled depancreatized dogs were placed on one of three isocaloric diets: regular chow diet once daily (Chow) or a simple nutrient diet (ND) that was given either once daily (ND-4) or infused continuously (ND-C). Intraportal insulin was infused to maintain euglycemia. After 5 days net hepatic (NHGU) and muscle (MGU) glucose uptake and oxidation were assessed at euglycemia (120 mg/dl) and hyperglycemia (200 mg/dl) in the presence of basal insulin. While hyperglycemia increased both NHGU and MGU in Chow, NHGU was amplified in both groups receiving ND. The increase was associated with enhanced activation of glycogen synthase, glucose oxidation and suppression of pyruvate dehydrogenase kinase-4 (PDK-4). Accelerated glucose-dependent muscle glucose uptake was only evident with ND-C. This was associated with a decrease in PDK-4 expression and an increase in AMP-activated protein kinase (AMPK) phosphorylation. Interestingly, ND-C markedly increased hepatic FGF-21 expression. Thus, augmentation of carbohydrate disposal in the liver, as opposed to the muscle, is not dependent on the pattern of nutrient delivery.

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Time course of the hepatic adaptation to TPN: interaction with glycogen depletion

Cited by 9 publications

References 27 publications

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

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

Route-dependent effect of nutritional support on liver glucose uptake

Liver, but Not Muscle, Has an Entrainable Metabolic Memory

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