ArticleDiabetes2008
Increased GABAergic tone in the ventromedial hypothalamus contributes to suppression of counterregulatory responses after antecedent hypoglycemia.
Article in Diabetes, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
80 citing papers in PubMed, 2 syntheses or guidelines pooled it, 106 citations in OpenAlex.
- Mechanisms and Pathogenesis of Diabetic Cognitive Impairment: A Comprehensive Review.Aging and disease · 2025Pooled it
- Recommendations for recognizing, risk stratifying, treating, and managing children and adolescents with hypoglycemia.Frontiers in endocrinology · 2024Pooled it
- Effects of ventromedial hypothalamic nucleus GAD gene knockdown on growth hormone-releasing hormone neuron transcriptomic profile in female rats.Molecular biology reports · 2026Article
- Comparison of ventromedial hypothalamic nucleus growth hormone-releasing hormone neuron counterregulatory neurochemical marker gene expression in young adult versus middle-aged male and female rats.IBRO neuroscience reports · 2025Article
- Sex-specific recurrent insulin-induced hypoglycemia (RIIH) effects on ventromedial hypothalamic nucleus astrocyte metabolic sensor expression and glycogen metabolism.Neuroscience · 2025Article
- Astrocyte glucose-6-phosphatase-Beta regulates ventromedial hypothalamic nucleus glucose counterregulatory neurotransmission and systemic hormone profiles.Neuropeptides · 2025Article
- Neuroimmune axis: Linking environmental factors to pancreatic β-cell dysfunction in Diabetes.Brain, behavior, & immunity - health · 2025Article
- Article
- Intestinal glucagon-like peptide-1: A new player associated with impaired counterregulatory responses to hypoglycaemia in type 1 diabetic mice.World journal of diabetes · 2024Article
- Hypoglycemia and Alzheimer Disease Risk: The Possible Role of Dasiglucagon.Cellular and molecular neurobiology · 2024Review
- Dorsomedial Ventromedial Hypothalamic Nucleus Growth Hormone-Releasing Hormone Neuron Steroidogenic Factor-1 Gene Targets in Female Rat.ASN neuro · 2024Article
- Experimental pharmacological approaches to reverse impaired awareness of hypoglycemia-a review.Frontiers in pharmacology · 2024Review
- Differential G Protein-Coupled Estrogen Receptor-1 Regulation of Counter-Regulatory Transmitter Marker and 5'-AMP-Activated Protein Kinase Expression in Ventrolateral versus Dorsomedial Ventromedial Hypothalamic Nucleus.Neuroendocrinology · 2024Article
- α-cell electrophysiology and the regulation of glucagon secretion.The Journal of endocrinology · 2023Review
- Carotid body: an emerging target for cardiometabolic co-morbidities.Experimental physiology · 2023Review
- Function of the GABAergic System in Diabetic Encephalopathy.Cellular and molecular neurobiology · 2023Review
- Current and future therapies to treat impaired awareness of hypoglycemia.Frontiers in pharmacology · 2023Review
- Remembrance of things past: The consequences of recurrent hypoglycaemia in diabetes.Diabetic medicine : a journal of the British Diabetic Association · 2022Review
- Single-cell multiplex qPCR evidence for sex-dimorphic glutamate decarboxylase, estrogen receptor, and 5'-AMP-activated protein kinase alpha subunit mRNA expression by ventromedial hypothalamic nucleus GABAergic neurons.Journal of chemical neuroanatomy · 2022Article
- Sleep deprivation prevents counterregulatory adaptation to recurrent hypoglycaemia.Diabetologia · 2022Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
objectiveWe have previously demonstrated that modulation of gamma-aminobutyric acid (GABA) inhibitory tone in the ventromedial hypothalamus (VMH), an important glucose-sensing region in the brain, modulates the magnitude of glucagon and sympathoadrenal responses to hypoglycemia. In the current study, we examined whether increased VMH GABAergic tone may contribute to suppression of counterregulatory responses after recurrent hypoglycemia. RESEARCH DESIGN AND
methodsTo test this hypothesis, we quantified expression of the GABA synthetic enzyme, glutamic acid decarboxylase (GAD), in the VMH of control and recurrently hypoglycemic rats. Subsequently, we used microdialysis and microinjection techniques to assess changes in VMH GABA levels and the effects of GABA(A) receptor blockade on counterregulatory responses to a standardized hypoglycemic stimulus.
resultsQuantitative RT-PCR and immunoblots in recurrently hypoglycemic animals revealed that GAD(65) mRNA and protein were increased 33 and 580%, respectively. Basal VMH GABA concentrations were more than threefold higher in recurrently hypoglycemic animals. Furthermore, whereas VMH GABA levels decreased in both control and recurrently hypoglycemic animals with the onset of hypoglycemia, the fall was not significant in recurrently hypoglycemic rats. During hypoglycemia, recurrently hypoglycemic rats exhibited a 49-63% reduction in glucagon and epinephrine release. These changes were reversed by delivery of a GABA(A) receptor antagonist to the VMH.
conclusionsOur data suggest that recurrent hypoglycemia increases GABAergic inhibitory tone in the VMH and that this, in turn, suppresses glucagon and sympathoadrenal responses to subsequent bouts of acute hypoglycemia. Thus, hypoglycemia-associated autonomic failure may be due in part to a relative excess of the inhibitory neurotransmitter, GABA, within the VMH.
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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.