Hepatic Denervation Alters the Transition from the Fed to the Food-Deprived State in Conscious Dogs

Moore, Mary Courtney; Pagliassotti, Michael J.; Wasserman, David H.; Goldstein, Richard E.; Asher, Jordan; Neal, Doss W.; Cherrington, Alan D.

doi:10.1093/jn/123.10.1739

Cited by 17 publications

(17 citation statements)

References 11 publications

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“…Because laboratory rats consume 80% of their total daily amount of food during nocturnal periods (34), these animals were effectively fasted for closer to 24 h, leading to a large reduction in glycogen stores in the rat. The disparities between the studies of Bergeron and colleagues and the current study showing an AICAR stimulation of glucose production can be attributed to differences in glycogen, as the liver of the 18-hϪfasted dog model used in this study contained ϳ65 mg glycogen/g liver (35) and gluconeogenesis is only 5-25% of NHGO (36). They are unlikely to be due to a species difference, as others have reported a dramatic increase in hepatic glycogen breakdown after administration of AICAR in 5-hϪfasted rats (12).…”

Section: Discussioncontrasting

confidence: 83%

Portal Venous 5-Aminoimidazole-4-Carboxamide-1-β-d-Ribofuranoside Infusion Overcomes Hyperinsulinemic Suppression of Endogenous Glucose Output

et al. 2005

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AMP-activated protein kinase (AMPK) plays a key role in regulating metabolism, serving as a metabolic master switch. The aim of this study was to assess whether increased concentrations of the AMP analog, 5-aminoimidazole-4-carboxamide-1-␤-D-ribosyl-5-monophosphate, in the liver would create a metabolic response consistent with an increase in whole-body metabolic need. Dogs had sampling (artery, portal vein, hepatic vein) and infusion (vena cava, portal vein) catheters and flow probes (hepatic artery, portal vein) implanted >16 days before a study. Protocols consisted of equilibration (؊130 to ؊30 min), basal (؊30 to 0 min), and hyperinsulinemic-euglycemic or -hypoglycemic clamp periods (0 -150 min). At t ‫؍‬ 0 min, somatostatin was infused and glucagon was replaced in the portal vein at basal rates. An intraportal hyperinsulinemic (2 mU ⅐ kg ؊1 ⅐ min ؊1) infusion was also initiated at this time. Glucose was clamped at hypoglycemic or euglycemic levels in the presence (H-AIC, n ‫؍‬ 6; E-AIC, n ‫؍‬ 6) or absence (H-SAL, n ‫؍‬ 6; E-SAL, n ‫؍‬ 6) of a portal venous 5-aminoimidazole-4-carboxamide-ribofuranoside (AICAR) infusion (1 mg ⅐ kg ؊1 ⅐ min ؊1) initiated at t ‫؍‬ 60 min. In the presence of intraportal saline, glucose was infused into the vena cava to match glucose levels seen with intraportal AICAR. Glucagon remained fixed at basal levels, whereas insulin rose similarly in all groups. Glucose fell to 50 ؎ 2 mg/dl by t ‫؍‬ 60 min in hypoglycemic groups and remained at 105 ؎ 3 mg/dl in euglycemic groups. Endogenous glucose production (R a ) was similarly suppressed among groups in the presence of euglycemia or hypoglycemia before t ‫؍‬ 60 min and remained suppressed in the H-SAL and E-SAL groups. However, intraportal AICAR infusion stimulated R a to increase by 2.5 ؎

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Section: Discussioncontrasting

confidence: 83%

Portal Venous 5-Aminoimidazole-4-Carboxamide-1-β-d-Ribofuranoside Infusion Overcomes Hyperinsulinemic Suppression of Endogenous Glucose Output

et al. 2005

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“…5), net glycogenolysis was 1.25 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 . The derived glycogenolytic rates after an overnight fast and during prolonged fasting are consistent with rough approximations of the glycogenolytic rates derived from published hepatic glycogen measurements compiled by Moore et al (38) and Hendrick et al (22) at various fasted states. If one plots their data and assumes that the decline in glycogen mass is linear over time, the net glycogenolytic rate is Ϸ2.0 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 at 20 h and Ϸ0.7 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 at 40 h of fasting.…”

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confidence: 85%

Effects of fasting and glucocorticoids on hepatic gluconeogenesis assessed using two independent methods in vivo

Goldstein

Rossetti

Palmer

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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. Effects of fasting and glucocorticoids on hepatic gluconeogenesis assessed using two independent methods in vivo. Am J Physiol Endocrinol Metab 283: E946-E957, 2002; 10.1152/ajpendo.00320.2002The purpose of this study was to compare the assessment of gluconeogenesis (GNG) in the overnight-and prolonged-fasted states and during chronic hypercortisolemia using the arteriovenous difference and [ 14 C]phosphoenolpyruvate-liver biopsy techniques as well as a combination of the two. Two weeks before a study, catheters and flow probes were implanted in the hepatic and portal veins and femoral artery of dogs. Animals were studied after an 18-h fast (n ϭ 8), a 42-or 66-h fast (n ϭ 7), and an 18-h fast plus a continuous infusion of cortisol (3.0 g⅐kg Ϫ1 ⅐min Ϫ1) for 72 h (n ϭ 7). Each experiment consisted of an 80-min tracer ([3-3 H]glucose and [U-14 C]alanine) and dye equilibration period (Ϫ80 to 0 min) and a 45-min sampling period. In the cortisoltreated group, plasma cortisol increased fivefold. In the overnight-fasted group, total GNG flux rate (GNG flux), conversion of glucose 6-phosphate to glucose (GNG G-6-P3 Glc), glucose cycling, and maximal GNG flux rate (GNG max) were 0.95 Ϯ 0.14, 0.65 Ϯ 0.06, 0.62 Ϯ 0.06, and 0.70 Ϯ 0.09 mg⅐kg Ϫ1 ⅐min Ϫ1, respectively. In the prolonged-fasted group, they were 1.50 Ϯ 0.18, 1.18 Ϯ 0.13, 0.40 Ϯ 0.07, and 1.28 Ϯ 0.10 mg⅐kg Ϫ1 ⅐min Ϫ1, whereas in the cortisol-treated group they were 1.64 Ϯ 0.33, 0.99 Ϯ 0.29, 1.32 Ϯ 0.24, and 0.91 Ϯ 0.13 mg⅐kg Ϫ1 ⅐min Ϫ1. These results demonstrate that GNG G-6-P3 Glc and GNGmax were almost identical. However, these rates were 15-38% lower than GNG flux generated by a combination of the two methods. This difference was most apparent in the steroid-treated group, where the combination of the two methods (GNG flux ) detected a significant increase in gluconeogenic flux.fasting; cortisol THE QUEST TO DEVELOP accurate methods for determining the rate of gluconeogenesis in vivo is ongoing. Many early studies used tracer methods or arteriovenous (a-v) difference techniques to assess the gluconeogenic rate in vivo (12,23,27,28). In 1977, Chiasson et al. (5) combined these two approaches for the assessment of gluconeogenesis in the dog. The latter approach yielded two estimates of gluconeogenesis, the gluconeogenic efficiency (percent extracted gluconeogenic carbon converted to glucose) and the gluconeogenic conversion rate (the rate of glucose production from the gluconeogenic precursor given). Both represented minimal estimates of gluconeogenesis due largely to dilution of the tracer in the oxaloacetate (OAA) pool of the liver (25). This approach was further extended by calculating the minimal and maximal rates of gluconeogenesis from circulating gluconeogenic precursors (3, 16, 51). The maximal rate was derived by measuring the net hepatic uptakes of all gluconeogenic precursors using the a-v difference technique and assuming that they were quantitatively converted to glucose. The minimal rate was derived by multiplying the maximal rate of gluconeog...

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“…The shift from net hepatic lactate release to uptake is an indicator of the transition from the fed to the fasted state in the dog (29), as in the human (3,39). This raises the question whether the pregnant group should have been studied after a shorter period of fasting than the nonpregnant group in order for the groups to start from a more similar metabolic state.…”

Section: Discussionmentioning

confidence: 99%

Insulin action during late pregnancy in the conscious dog

Connolly¹,

Aglione²,

Smith³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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Our aim was to assess the magnitude of peripheral insulin resistance and whether changes in hepatic insulin action were evident in a canine model of late (3rd trimester) pregnancy. A 3-h hyperinsulinemic (5 mU·kg Ϫ1 ·min Ϫ1 ) euglycemic clamp was conducted using conscious, 18-h-fasted pregnant (P; n ϭ 6) and nonpregnant (NP; n ϭ 6) female dogs in which catheters for intraportal insulin infusion and assessment of hepatic substrate balances were implanted ϳ17 days before experimentation. Arterial plasma insulin rose from 11 Ϯ 2 to 192 Ϯ 24 and 4 Ϯ 2 to 178 Ϯ 5 U/ml in the 3rd h in NP and P, respectively. Glucagon fell equivalently in both groups. Basal net hepatic glucose output was lower in NP (1.9 Ϯ 0.1 vs. 2.4 Ϯ 0.2 mg·kg Ϫ1 ·min Ϫ1 , P Ͻ 0.05). Hyperinsulinemia completely suppressed hepatic glucose release in both groups (Ϫ0.4 Ϯ 0.2 and Ϫ0.1 Ϯ 0.2 mg·kg Ϫ1 ·min Ϫ1 in NP and P, respectively). More exogenous glucose was required to maintain euglycemia in NP (15.2 Ϯ 1.3 vs. 11.5 Ϯ 1.1 mg·kg Ϫ1 ·min Ϫ1 , P Ͻ 0.05). Nonesterified fatty acids fell similarly in both groups. Net hepatic gluconeogenic amino acid uptake with high insulin did not differ in NP and P. Peripheral insulin action is markedly impaired in this canine model of pregnancy, whereas hepatic glucose production is completely suppressed by high circulating insulin levels. insulin resistance; hepatic glucose production; lipolysis; ketogenesis; gluconeogenesis LATE PREGNANCY IS ACCOMPANIED by alterations in many metabolic processes, involving multiple maternal tissues, that allow the mother to balance her own nutritional needs with the increasing requirements of utero-placental-fetal tissues (14, 21). In the basal state, hepatic glucose production and ketogenesis are increased, indicating altered basal liver function, and fat and protein metabolism are clearly affected (1, 6 -8, 14, 21, 23, 24). Pregnancy is accompanied by the development of marked whole body insulin resistance in a variety of species (2,4,5,18,20,26,27,32,33). Use of the hyperinsulinemic euglycemic clamp technique in pregnant women revealed a marked reduction in the glucose infusion rate (up to ϳ24%) required to maintain euglycemia compared with nonpregnant controls, even with pharmacological elevation of insulin to levels of ϳ600 U/ml (33). Similar results obtained in clamp studies utilizing very high insulin levels in the pregnant rat (26) and rabbit (18) specifically revealed the significant attenuation of insulin's ability to stimulate glucose uptake in peripheral tissues in pregnancy.The techniques necessary to make thorough assessments of hepatic substrate metabolism are too invasive for use in pregnant women. We recently described a conscious canine model of pregnancy (8) that employs chronic catheterization techniques to make such assessments. We showed that this canine model has basal characteristics similar to those of pregnant women, indicating that it would be useful for studying the regulation of metabolic changes during pregnancy. The aims of the present study were to fur...

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Hepatic Denervation Alters the Transition from the Fed to the Food-Deprived State in Conscious Dogs

Cited by 17 publications

References 11 publications

Portal Venous 5-Aminoimidazole-4-Carboxamide-1-β-d-Ribofuranoside Infusion Overcomes Hyperinsulinemic Suppression of Endogenous Glucose Output

Portal Venous 5-Aminoimidazole-4-Carboxamide-1-β-d-Ribofuranoside Infusion Overcomes Hyperinsulinemic Suppression of Endogenous Glucose Output

Effects of fasting and glucocorticoids on hepatic gluconeogenesis assessed using two independent methods in vivo

Insulin action during late pregnancy in the conscious dog

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