ArticleThe Journal of clinical investigation2016
Hepatic glycogen can regulate hypoglycemic counterregulation via a liver-brain axis.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Article
- Development of a severe rat refeeding syndrome model and mathematical modeling of the associated hypophosphatemia.NPJ systems biology and applications · 2026Article
- Aberrant hepatic glycogenolysis and elevated insulin clearance can lead to major glucose irregularities in type 2 diabetes: insights from system identification.Frontiers in physiology · 2026Article
- Review
- Fasting Lowers Glucagon Levels Under Basal Conditions and During Insulin-Induced Hypoglycemia in Individuals With Type 1 Diabetes.Diabetes · 2025Article
- The effects of initiating a 24-hour fast with a low versus a high carbohydrate shake on glycemic control in older adults: a randomized crossover study.Nutrition & metabolism · 2025Article
- Metabolic Crosstalk between Liver and Brain: From Diseases to Mechanisms.International journal of molecular sciences · 2024Review
- Short-term fasting lowers glucagon levels under euglycemic and hypoglycemic conditions in healthy humans.JCI insight · 2023Article
- Ligand-switchable nanoparticles resembling viral surface for sequential drug delivery and improved oral insulin therapy.Nature communications · 2022Article
- Somatostatin Receptor Antagonism Reverses Glucagon Counterregulatory Failure in Recurrently Hypoglycemic Male Rats.Endocrinology · 2021Article
- Leptin treatment prevents impaired hypoglycemic counterregulation induced by exposure to severe caloric restriction or exposure to recurrent hypoglycemia.Autonomic neuroscience : basic & clinical · 2021Article
- Liver glycogen-induced enhancements in hypoglycemic counterregulation require neuroglucopenia.American journal of physiology. Endocrinology and metabolism · 2021Article
- Safety of surgical denervation of the common hepatic artery in insulin-resistant dogs.Physiological reports · 2021Article
- The kinetics of glucagon action on the liver during insulin-induced hypoglycemia.American journal of physiology. Endocrinology and metabolism · 2020Article
- Article
- The integrative biology of type 2 diabetes.Nature · 2019Review
- Targeting insulin to the liver corrects defects in glucose metabolism caused by peripheral insulin delivery.JCI insight · 2019Article
- Salvianolate Reduces Glucose Metabolism Disorders in Dimethylnitrosamine-Induced Cirrhotic Rats.Chinese journal of integrative medicine · 2018Article
- Recurrent hypoglycemia inhibits the counterregulatory response by suppressing adrenal activity.The Journal of clinical investigation · 2018Article
- Morning Hyperinsulinemia Primes the Liver for Glucose Uptake and Glycogen Storage Later in the Day.Diabetes · 2018Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Liver glycogen is important for the counterregulation of hypoglycemia and is reduced in individuals with type 1 diabetes (T1D). Here, we examined the effect of varying hepatic glycogen content on the counterregulatory response to low blood sugar in dogs. During the first 4 hours of each study, hepatic glycogen was increased by augmenting hepatic glucose uptake using hyperglycemia and a low-dose intraportal fructose infusion. After hepatic glycogen levels were increased, animals underwent a 2-hour control period with no fructose infusion followed by a 2-hour hyperinsulinemic/hypoglycemic clamp. Compared with control treatment, fructose infusion caused a large increase in liver glycogen that markedly elevated the response of epinephrine and glucagon to a given hypoglycemia and increased net hepatic glucose output (NHGO). Moreover, prior denervation of the liver abolished the improved counterregulatory responses that resulted from increased liver glycogen content. When hepatic glycogen content was lowered, glucagon and NHGO responses to insulin-induced hypoglycemia were reduced. We conclude that there is a liver-brain counterregulatory axis that is responsive to liver glycogen content. It remains to be determined whether the risk of iatrogenic hypoglycemia in T1D humans could be lessened by targeting metabolic pathway(s) associated with hepatic glycogen repletion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.