What question did this study set out to answer?

This study aims to investigate how the route of insulin delivery affects glucose disposal between the liver and muscle in dogs with metabolic dysfunction.

June 7, 2026

2484-P: The Clinical Effect of Peripheral Insulin Delivery in Dogs Fed a High Fat and Fructose Diet

Key Points

This study aims to investigate how the route of insulin delivery affects glucose disposal between the liver and muscle in dogs with metabolic dysfunction.
Dogs (n=6/group) were fed a chow (C) or high fat and fructose (FF) diet for 4 weeks
Insulin was infused either into the portal vein (PV) or via leg vein (LV), with glucagon infusion to disable pancreatic activity
Postprandial hyperglycemia was induced through glucose infusion while monitoring hepatic and muscle glucose uptake.
Net hepatic glucose uptake was significantly reduced in FF-fed dogs compared to chow-fed counterparts
Muscle glucose uptake was approximately 2.5 times greater in the FF+LV insulin group compared to the FF+PV insulin group
Neither portal nor leg-vein insulin delivery overcame the reduction in liver glucose uptake due to the FF diet.

Abstract

Introduction and Objective: Clinical (subcutaneous) insulin delivery abolishes the endogenous portal vein (PV) to arterial insulin gradient, leading to relative hepatic under-insulinization as well as excess insulin exposure of muscle. Our aim was to determine how route of insulin delivery affects liver vs muscle glucose disposal in dogs with high fat and fructose (FF) induced metabolic dysfunction. Methods: Dogs (n=6/group) were fed a chow (C) or FF diet for 4 weeks. Somatostatin was used to disable the pancreas and basal glucagon was infused. Postprandial hyperglycemia was created with PV (4 mg/kg/min) and leg vein (LV) glucose (infused as needed), while insulin was infused (1.2 mU/kg/min) either into the PV or a LV. Results: PV insulin was ~2x greater with PV infusion whereas arterial insulin was ~2x greater with LV infusion. Net hepatic glucose uptake was markedly reduced in FF compared to C-fed dogs. While the diet’s effect on NHGU was not altered by route of insulin delivery (6.2±0.5, 2.4±0.2 and 2.2±2.2 mg/kg/min in the C+PV ins, FF+PV ins and FF+LV ins groups, respectively), MGU was ~2.5x greater in FF+LV ins vs FF+PV ins. Conclusion: While PV nor LV insulin were able to overcome the severe reduction in liver glucose uptake caused by the FF diet, LV insulin delivery, in addition, caused much greater MGU, an effect that increases hypoglycemic risk. Therefore, diet induced impairment of postprandial hepatic glucose uptake cannot be normalized by increasing the dose of peripherally delivered insulin. Disclosure G. Kraft: None. K. Yankey: None. B. Farmer: None. H. Waterman: None. M. Lee: None. J. Hastings: None. D. Edgerton: None. Funding NIH RO1DK018243

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Cite This Study

KRAFT et al. (Fri,) studied this question.

synapsesocial.com/papers/6a250b2d7def13d035e1b2e0 https://doi.org/https://doi.org/10.2337/db26-2484-p

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