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Profound Sensitivity of the Liver to the Direct Effect of Insulin Allows Peripheral Insulin Delivery to Normalize Hepatic but Not Muscle Glucose Uptake in the Healthy Dog. | LitMetric

AI Article Synopsis

  • Endogenous insulin plays a crucial role in regulating how the liver manages glucose after eating, but this process gets disrupted in diabetes.
  • When insulin is delivered under the skin, it leads to an imbalance where the liver receives less insulin compared to the rest of the body, resulting in higher insulin levels outside the liver, which can contribute to metabolic diseases.
  • In healthy dogs, even when insulin was infused into a peripheral vein, the liver still effectively stored glucose, showing its strong sensitivity to insulin, whereas the extra insulin in the body led to increased glucose uptake in muscles, highlighting a mismatch in how glucose is processed.

Article Abstract

Endogenous insulin secretion is a key regulator of postprandial hepatic glucose metabolism, but this process is dysregulated in diabetes. Subcutaneous insulin delivery alters normal insulin distribution, causing relative hepatic insulin deficiency and peripheral hyperinsulinemia, a major risk factor for metabolic disease. Our aim was to determine whether insulin's direct effect on the liver is preeminent even when insulin is given into a peripheral vein. Postprandial-like conditions were created (hyperinsulinemia, hyperglycemia, and a positive portal vein to arterial glucose gradient) in healthy dogs. Peripheral (leg vein) insulin infusion elevated arterial and hepatic levels 8.0-fold and 2.8-fold, respectively. In one group, insulin's full effects were allowed. In another, insulin's indirect hepatic effects were blocked with the infusion of triglyceride, glucagon, and inhibitors of brain insulin action (intracerebroventricular) to prevent decreases in plasma free fatty acids and glucagon, while blocking increased hypothalamic insulin signaling. Despite peripheral insulin delivery the liver retained its full ability to store glucose, even when insulin's peripheral effects were blocked, whereas muscle glucose uptake markedly increased, creating an aberrant distribution of glucose disposal between liver and muscle. Thus, the healthy liver's striking sensitivity to direct insulin action can overcome the effect of relative hepatic insulin deficiency, whereas excess insulin in the periphery produces metabolic abnormalities in nonhepatic tissues.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871195PMC
http://dx.doi.org/10.2337/db22-0471DOI Listing

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