ArticleDiabetes2010
Brain insulin action regulates hypothalamic glucose sensing and the counterregulatory response to hypoglycemia.
Article in Diabetes, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 100 citations in OpenAlex.
- Limited Diagnostic Utility of Cortisol and Growth Hormone Levels Obtained during Hypoglycemia in Children.Hormone research in paediatrics · 2026Article
- TRIM5 integrates hypoglycemic stress and influenza infection.Nature communications · 2026Article
- Type 2 Diabetes Mellitus Exacerbates Pathological Processes of Parkinson's Disease: Insights from Signaling Pathways Mediated by Insulin Receptors.Neuroscience bulletin · 2025Review
- Cellular Profile of Subfornical Organ Insulin Receptors in Mice.Biomolecules · 2024Article
- Brain Regulation of Cardiac Function during Hypoglycemia.Metabolites · 2023Review
- Cure of Alzheimer's Dementia in Many Patients by Using Intranasal Insulin to Augment an Inadequate Counter-Reaction, Edaravone to Scavenge ROS, and 1 or 2 Other Drugs to Address Affected Brain Cells.Journal of clinical medicine · 2023Article
- Evidence for preserved insulin responsiveness in the aging rat brain.GeroScience · 2022Article
- Insulin action in the brain: cell types, circuits, and diseases.Trends in neurosciences · 2022Review
- Article
- Homeostatic Regulation of Glucose Metabolism by the Central Nervous System.Endocrinology and metabolism (Seoul, Korea) · 2022Article
- AKT ISOFORMS-AS160-GLUT4: The defining axis of insulin resistance.Reviews in endocrine & metabolic disorders · 2021Review
- The brain as an insulin-sensitive metabolic organ.Molecular metabolism · 2021Review
- Brain-gut-liver interactions across the spectrum of insulin resistance in metabolic fatty liver disease.World journal of gastroenterology · 2021Review
- Insulin action in the brain regulates both central and peripheral functions.American journal of physiology. Endocrinology and metabolism · 2021Review
- Insulin actions on hypothalamic glucose-sensing neurones.Journal of neuroendocrinology · 2021Review
- Glucose transporters in brain in health and disease.Pflugers Archiv : European journal of physiology · 2020Review
- Ventromedial hypothalamus glucose-inhibited neurones: A role in glucose and energy homeostasis?Journal of neuroendocrinology · 2020Review
- Duodenal-Jejunal Bypass Ameliorates Type 2 Diabetes Mellitus by Activating Insulin Signaling and Improving Glucose Utilization in the Brain.Obesity surgery · 2020Article
- Subfornical organ insulin receptors tonically modulate cardiovascular and metabolic function.Physiological genomics · 2019Article
- Dissecting the Brain/Islet Axis in Metabesity.Genes · 2019Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveAn impaired ability to sense and appropriately respond to insulin-induced hypoglycemia is a common and serious complication faced by insulin-treated diabetic patients. This study tests the hypothesis that insulin acts directly in the brain to regulate critical glucose-sensing neurons in the hypothalamus to mediate the counterregulatory response to hypoglycemia. RESEARCH DESIGN AND
methodsTo delineate insulin actions in the brain, neuron-specific insulin receptor knockout (NIRKO) mice and littermate controls were subjected to graded hypoglycemic (100, 70, 50, and 30 mg/dl) hyperinsulinemic (20 mU/kg/min) clamps and nonhypoglycemic stressors (e.g., restraint, heat). Subsequently, counterregulatory responses, hypothalamic neuronal activation (with transcriptional marker c-fos), and regional brain glucose uptake (via (14)C-2deoxyglucose autoradiography) were measured. Additionally, electrophysiological activity of individual glucose-inhibited neurons and hypothalamic glucose sensing protein expression (GLUTs, glucokinase) were measured.
resultsNIRKO mice revealed a glycemia-dependent impairment in the sympathoadrenal response to hypoglycemia and demonstrated markedly reduced (3-fold) hypothalamic c-fos activation in response to hypoglycemia but not other stressors. Glucose-inhibited neurons in the ventromedial hypothalamus of NIRKO mice displayed significantly blunted glucose responsiveness (membrane potential and input resistance responses were blunted 66 and 80%, respectively). Further, hypothalamic expression of the insulin-responsive GLUT 4, but not glucokinase, was reduced by 30% in NIRKO mice while regional brain glucose uptake remained unaltered.
conclusionsChronically, insulin acts in the brain to regulate the counterregulatory response to hypoglycemia by directly altering glucose sensing in hypothalamic neurons and shifting the glycemic levels necessary to elicit a normal sympathoadrenal response.
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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.