Hepatic Portal Vein Cannulation for Infusion and Blood Sampling in Freely Moving Rats

Strubbe, J.H.; Bruggink, J.E.; Steffens, A.B.

doi:10.1016/s0031-9384(98)00248-0

Cited by 17 publications

(13 citation statements)

References 14 publications

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“…Portal veins were cannulated as described (Strubbe et al, 1999). The catheter (0.025 mm OD × 0.012 mm ID, Braintree Scientific), prefilled with 55% (w/v) polyvinylpyrrolidone (Sigma) in heparin (100 IU/ml saline) to prevent clotting, was anchored to the abdominal wall, and its free end was inserted under the skin and tunneled to a small midline incision slightly distal to the scapula on the back.…”

Section: Methodsmentioning

confidence: 99%

Identification of a Physiologically Relevant Endogenous Ligand for PPARα in Liver

Chakravarthy

Lodhi

et al. 2009

Cell

487

425

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Summary PPARα is activated by drugs to treat human disorders of lipid metabolism. Its endogenous ligand is unknown. PPARα-dependent gene expression is impaired with inactivation of fatty acid synthase (FAS), suggesting that FAS is involved in generation of a PPARα ligand. Here we demonstrate the FAS-dependent presence of a phospholipid bound to PPARα isolated from mouse liver. Binding was increased under conditions that induce FAS activity and displaced by systemic injection of a PPARα agonist. Mass spectrometry identified the species as 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Knockdown of CEPT1, required for phosphatidylcholine synthesis, suppressed PPARα-dependent gene expression. Interaction of 16:0/18:1-GPC with the PPARα ligand binding domain and co-activator peptide motifs was comparable to PPARα agonists, but interactions with PPARδ were weak and none were detected with PPARγ. Portal vein infusion of 16:0/18:1-GPC induced PPARα-dependent gene expression and decreased hepatic steatosis. These data suggest that 16:0/18:1-GPC is a physiologically relevant endogenous PPARα ligand.

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Section: Methodsmentioning

confidence: 99%

Identification of a Physiologically Relevant Endogenous Ligand for PPARα in Liver

Chakravarthy

Lodhi

et al. 2009

Cell

487

425

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“…The silastic end of the catheter was connected to a Luer-lock assembly which was then fixed onto the skull by stainless steel screws and dental cement. Before closing the catheter with a cap, 0.15 ml of polyvinylpyrrolidone (Sigma-Aldrich, St. Louis) in heparin (500 IU/ml) was infused into the catheter [58]. For catheter maintenance, 0.1 ml of isotonic sterile saline-heparin solution (100 IU/ml) was infused into the catheter for the first two recovery days.…”

Section: Methodsmentioning

confidence: 99%

“…On training trials, the syringe pumps were activated by the rat’s licking responses and delivered a 10 ml infusion over a 2-h period. These infusion parameters were adopted from Gowans [25], and the rate of 8.3 mg glucose/min is within the physiological range for glucose absorption from the gut [58,63]. …”

Section: Methodsmentioning

confidence: 99%

Post-oral infusion sites that support glucose-conditioned flavor preferences in rats

Ackroff

Yiin

Sclafani

2010

Physiology & Behavior

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Rats learn to prefer a flavored solution (CS+) paired with a gastrointestinal glucose infusion over an alternate flavor (CS−) paired with a non-caloric infusion. Prior work implicates a post-gastric site of glucose action, which is the focus of this study. In Exp. 1, male rats (8-10/group) were infused in the duodenum (ID), mid-jejunum (IJ), or distal ileum (II) with 8% glucose or water as they drank saccharin-sweetened CS+ and CS− solutions, respectively, in one-bottle 30-min sessions. Two-bottle tests (no infusions) were followed by a second train-test cycle. By the second test, the ID and IJ groups preferred the CS+ (69%, 67%) to the CS− but the II group did not (48%). Satiation tests showed that ID and IJ infusions of glucose reduced intake of a palatable solution similarly, while II infusions were ineffective. In Exp. 2, rats (10/group) drank CS solutions in one-bottle, 30-min sessions and were given 2-h ID or hepatic portal vein (HP) infusions. The CS+ and CS− were paired with 10 ml infusions of 10% glucose and 0.9% saline, respectively. Following 8 training sessions, the ID group preferred the CS+ (67%) to the CS− but the HP g roup did not (47%) in a two-bottle test. The similar CS+ preferences displayed by ID and IJ, but not II groups implicate the jejunum as a critical site for glucose-conditioned preferences. A preabsorptive glucose action is indicated by the CS+ preference displayed by ID but not HP rats in Exp. 2. Our data were obtained with non-nutritive CS solutions. HP glucose infusions are reported to condition preferences for a flavored food that itself has pre-and postabsorptive actions. Thus, there may be multiple sites for glucose conditioning with the upper or mid-intestines being the first site of action.

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“…To enable drug administration, cannulas (PE-50 intramedic polyethylene tubing; BD Biosciences, San Jose, CA) were implanted in the duodenum and blood vessels (jugular and portal vein) of the rats. Portal vein cannulation was performed according to the method described by Strubbe et al (1999) with slight modifications. The surgery was performed under anesthesia (9% ketamine and 1% xylazine solution, i.p.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic-Pharmacodynamic Analysis of the Glucose-Lowering Effect of Metformin in Diabetic Rats Reveals First-Pass Pharmacodynamic Effect

Stepensky

Friedman²,

Raz³

et al. 2002

Drug Metab Dispos

118

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This article is available online at http://dmd.aspetjournals.org ABSTRACT:Metformin, a commonly used antidiabetic drug, exerts its glucoselowering effect due to metabolic activities at several sites of action (biophases), including liver, intestine, muscle cells, and adipocytes. The relative contribution of the individual biophases to the overall glucose-lowering effect is not known. Thus, the aims of this investigation were to study the influence of mode of drug administration on the kinetics of glucose-lowering action of metformin in diabetic rats and identify the contribution of different sites of action to the overall response. Streptozotocin diabetic rats received metformin in crossover fashion via intraduodenal, intravenous, and intraportal routes as bolus dose or infusion regimens designed to yield similar pharmacokinetic profiles. Metformin plasma concentrations and blood glucose levels were measured following each mode of administration. Despite the similarity in the concentration-time profiles obtained for different routes of metformin administration, intraduodenal administration produced larger response than intraportal metformin infusion, and lowest response was observed following intravenous administration. This finding indicates that a significant "first-pass" pharmacodynamic effect, which occurs in the presystemic sites of action (liver and the gastrointestinal wall), contributes to the overall glucose-lowering response of metformin. We applied a combined pharmacokinetic-pharmacodynamic modeling approach to study the nature of the first-pass pharmacodynamic effect. The observed data were successfully described by a novel integrated indirect response pharmacokinetic-pharmacodynamic model that revealed a correlation between the temporal metformin concentrations that transit the portal vein and through the gut wall rather than with drug concentrations that accumulated in the liver and the intestinal wall.Metformin, a biguanide glucose-lowering agent, is commonly used for management of type 2 diabetes. Despite the wide clinical use of metformin, the mechanism of its action is not fully understood. The glucose-lowering effect of metformin is apparently composed of a combination of several distinct activities in various organs and tissues (Hermann and Melander, 1992;Cusi and DeFronzo, 1998), including: 1) decreased hepatic glucose output due to decreased hepatic gluconeogenesis and increased glycogenesis and lipogenesis (Christiansen and Hellerstein, 1998); 2) reduced rate of intestinal glucose absorption (Wilcock and Bailey, 1991); and 3) increased glucose uptake by muscle cells and adipocytes (Bailey et al., 1996). The multifactorial mechanism of action of metformin and the complex nature of glucose homeostasis in vivo obscures the dose-response relationship of the metabolic effects in individual organs and tissues (Wiernsperger, 1996). As a result, the relative significance of the above-mentioned sites of metformin action (biophases) to produce metabolic effects remains unknown and is still a matter ...

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Hepatic Portal Vein Cannulation for Infusion and Blood Sampling in Freely Moving Rats

Cited by 17 publications

References 14 publications

Identification of a Physiologically Relevant Endogenous Ligand for PPARα in Liver

Identification of a Physiologically Relevant Endogenous Ligand for PPARα in Liver

Post-oral infusion sites that support glucose-conditioned flavor preferences in rats

Pharmacokinetic-Pharmacodynamic Analysis of the Glucose-Lowering Effect of Metformin in Diabetic Rats Reveals First-Pass Pharmacodynamic Effect

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