Magnitude of Negative Arterial-Portal Glucose Gradient Alters Net Hepatic Glucose Balance in Conscious Dogs

Pagliassotti, Michael J.; Myers, S. R.; Moore, Mary Courtney; Neal, Doss W.; Cherrington, Alan D.

doi:10.2337/diab.40.12.1659

Cited by 55 publications

(41 citation statements)

References 31 publications

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“…NHGU and net hepatic fractional glucose extraction were not higher with TPNϩEG than with TPN; however, arterial insulin levels were 40% lower with TPNϩEG. The arterial-portal glucose gradient shown with TPNϩEG was large enough to maximally activate the portal signal (1.0 Ϯ 0.1 mM) (21). As long as insulin is present at concentrations at or above basal, the ability of the portal signal to augment NHGU acutely (more than ϳ2 mg⅐kg Ϫ1 ⅐min Ϫ1 ) is independent of insulin levels (18).…”

Section: Discussionmentioning

confidence: 92%

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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Section: Discussionmentioning

confidence: 92%

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

View full text Add to dashboard Cite

show abstract

“…We chose an intraduodenal glucose infusion rate of 20 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 because Pagliassotti et al (59) have shown that the "portal signal" for enhanced hepatic glucose uptake is activated when glucose enters the portal vein at a rate as low as 10 mol ⅐ kg Ϫ1 ⅐ min…”

Section: Glp-1 In Type 1 Diabetesmentioning

confidence: 99%

“…The systemic rate of appearance of the intraduodenally infused glucose was clearly in excess of this rate, averaging 18.7 and 15.0 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 on the GLP-1 and saline study days. Assuming the liver took up at least a portion of the glucose presented to it, the intraportal appearance of glucose likely approximated the rate shown in the studies of Pagliassotti et al (59) to generate the maximal "portal signal" (i.e., 20 mol ⅐ kg Ϫ1 ⅐ min…”

mentioning

confidence: 99%

Effect of Glucagon-Like Peptide-1(7-36)-Amide on Initial Splanchnic Glucose Uptake and Insulin Action in Humans With Type 1 Diabetes

Vella¹,

Shah²,

Basu³

et al. 2001

Diabetes

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In vitro studies indicate that glucagon-like peptide-1(7-36)-amide (GLP-1) can enhance hepatic glucose uptake. To determine whether GLP-1 increases splanchnic glucose uptake in humans, we studied seven subjects with type 1 diabetes on two occasions. On both occasions, glucose was maintained at ϳ5.5 mmol/l during the night using a variable insulin infusion. On the morning of the study, a somatostatin, glucagon, and growth hormone infusion was started to maintain basal hormone levels. Glucose (containing [3 H]glucose) was infused via an intraduodenal tube at a rate of 20 mol ⅐ kg ؊1 ⅐ min ؊1 . Insulin concentrations were increased to ϳ500 pmol/l while glucose was clamped at ϳ8.8 mmol/l for the next 4 h by means of a variable intravenous glucose infusion labeled with [6,6-2 H 2 ]glucose. Surprisingly, the systemic appearance of intraduodenally infused glucose was higher (P ‫؍‬ 0.01) during GLP-1 infusion than saline infusion, indicating a lower (P < 0.05) rate of initial splanchnic glucose uptake (1.4 ؎ 1.5 vs. 4.8 ؎ 0.8 mol ⅐ kg ؊1 ⅐ min ؊1 ). On the other hand, flux through the hepatic uridine-diphosphate-glucose pool did not differ between study days (14.2 ؎ 5.5 vs. 13.0 ؎ 4.2 mol ⅐ kg ؊1 ⅐ min ؊1 ), implying equivalent rates of glycogen synthesis. GLP-1 also impaired (P < 0.05) insulin-induced suppression of endogenous glucose production (6.9 ؎ 2.9 vs. 1.3 ؎ 1.4 mol ⅐ kg ؊1 ⅐ min ؊1 ), but caused a time-dependent increase (P < 0.01) in glucose disappearance (93.7 ؎ 10.0 vs. 69.3 ؎ 6.3 mol ⅐ kg ؊1 ⅐ min ؊1 ; P < 0.01) that was evident only during the final hour of study. We conclude that in the presence of hyperglycemia, hyperinsulinemia, and enterally delivered glucose, GLP-1 increases total body but not splanchnic glucose uptake in humans with type 1 diabetes. Diabetes 50: 565-572, 2001 G lucagon-like peptide-1(7-36)-amide (GLP-1) and its analogues are being actively evaluated as a potential therapy for humans with type 1 diabetes (1-5). GLP-1 enhances insulin secretion, decreases glucagon secretion, and delays gastric emptying (6,7). In vitro studies also suggest that GLP-1 may have extrapancreatic effects (8,9). GLP-1 receptors are present in muscle (10,11), fat (8,12), and liver (13). In vitro studies have shown that GLP-1 can increase glucose uptake in each of these tissues and that its effects are additive to those of insulin (14,15). In contrast, results from in vivo studies have been less consistent. GLP-1 has been reported to increase glucose uptake during hyperglycemia and hyperinsulinemia in diabetic rats (16) and pancreatectomized dogs (17) and during euglycemia and hyperinsulinemia in humans with type 1 diabetes (18). On the other hand, GLP-1 has been reported to have no effect on insulin action during euglycemia and hyperinsulinemia in nondiabetic humans (19) and dogs (20) or during "prandial" insulin and glucose infusions in humans with type 2 diabetes (21).All of these studies evaluated insulin action during intravenous glucose infusion. This approach contrasts with the situation that occurs und...

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“…This may in part be due to stimulation of glycogen synthesis by intestinal incretins (28) and in part due to the generation of a "portal" signal to the liver (29,30). The latter has been shown to substantially enhance hepatic glucose uptake in dogs (29,30). If this also occurs in diabetic humans, then it may reverse the defect in hepatic glucokinase activity observed during intravenous glucose infusion, thereby normalizing postprandial splanchnic glucose uptake.…”

mentioning

confidence: 99%

“…Second, enterally administered glucose has been reported to result in greater hepatic glucose uptake than intravenously infused glucose (8,26,27). This may in part be due to stimulation of glycogen synthesis by intestinal incretins (28) and in part due to the generation of a "portal" signal to the liver (29,30). The latter has been shown to substantially enhance hepatic glucose uptake in dogs (29,30).…”

mentioning

confidence: 99%

Type 2 Diabetes Impairs Splanchnic Uptake of Glucose but Does Not Alter Intestinal Glucose Absorption During Enteral Glucose Feeding

et al. 2001

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We have previously reported that splanchnic glucose uptake, hepatic glycogen synthesis, and hepatic glucokinase activity are decreased in people with type 2 diabetes during intravenous glucose infusion. To determine whether these defects are also present during more physiological enteral glucose administration, we studied 11 diabetic and 14 nondiabetic volunteers using a combined organ catheterization-tracer infusion technique. Glucose was infused into the duodenum at a rate of 22 mol ⅐ kg ؊1 ⅐ min ؊1 while supplemental glucose was given intravenously to clamp glucose at ϳ10 mmol/l in both groups. Endogenous hormone secretion was inhibited with somatostatin, and insulin was infused to maintain plasma concentrations at ϳ300 pmol/l (i.e., twofold higher than our previous experiments). Total body glucose disappearance, splanchnic, and leg glucose extractions were markedly lower (P < 0.01) in the diabetic subjects than in the nondiabetic subjects. UDP-glucose flux, a measure of glycogen synthesis, was ϳ35% lower (P < 0.02) in the diabetic subjects than in the nondiabetic subjects. This was entirely accounted for by a decrease (P < 0.01) in the contribution of extracellular glucose because the contribution of the indirect pathway to hepatic glycogen synthesis was similar between groups. Neither endogenous and splanchnic glucose productions nor rates of appearance of the intraduodenally infused glucose in the portal vein differed between groups. In summary, both muscle and splanchnic glucose uptake are impaired in type 2 diabetes during enteral glucose administration. The defect in splanchnic glucose uptake appears to be due to decreased uptake of extracellular glucose, implying decreased glucokinase activity. Thus, abnormal hepatic and muscle (but not gut) glucose metabolism are likely to contribute to postprandial hyperglycemia in people with type 2 diabetes. Diabetes 50:1351-1362, 2001

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Magnitude of Negative Arterial-Portal Glucose Gradient Alters Net Hepatic Glucose Balance in Conscious Dogs

Cited by 55 publications

References 31 publications

Route-dependent effect of nutritional support on liver glucose uptake

Route-dependent effect of nutritional support on liver glucose uptake

Effect of Glucagon-Like Peptide-1(7-36)-Amide on Initial Splanchnic Glucose Uptake and Insulin Action in Humans With Type 1 Diabetes

Type 2 Diabetes Impairs Splanchnic Uptake of Glucose but Does Not Alter Intestinal Glucose Absorption During Enteral Glucose Feeding

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