ArticleDiabetes2011
Increased GABAergic output in the ventromedial hypothalamus contributes to impaired hypoglycemic counterregulation in diabetic rats.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
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Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 55 citations in OpenAlex.
- Recommendations for recognizing, risk stratifying, treating, and managing children and adolescents with hypoglycemia.Frontiers in endocrinology · 2024Pooled it
- Brain Mass (Energy) Resistant to Hyperglycaemic Oversupply: A Systematic Review.Frontiers in neuroscience · 2021Pooled it
- Acute Effects of Oral Dehydroepiandrosterone on Counterregulatory Responses During Repeated Hypoglycemia in Healthy Humans.Diabetes · 2016Trial
- Effects of ventromedial hypothalamic nucleus GAD gene knockdown on growth hormone-releasing hormone neuron transcriptomic profile in female rats.Molecular biology reports · 2026Article
- Experimental pharmacological approaches to reverse impaired awareness of hypoglycemia-a review.Frontiers in pharmacology · 2024Review
- Function of the GABAergic System in Diabetic Encephalopathy.Cellular and molecular neurobiology · 2023Review
- Consequences of recurrent hypoglycaemia on brain function in diabetes.Diabetologia · 2021Review
- Carvedilol prevents impairment of the counterregulatory response in recurrently hypoglycaemic diabetic rats.Endocrinology, diabetes & metabolism · 2021Article
- Pentobarbital Anesthesia Suppresses the Glucose Response to Acute Intermittent Hypoxia in Rat.Frontiers in physiology · 2021Article
- A GABAergic neural circuit in the ventromedial hypothalamus mediates chronic stress-induced bone loss.The Journal of clinical investigation · 2020Article
- Repeated hypoglycemia remodels neural inputs and disrupts mitochondrial function to blunt glucose-inhibited GHRH neuron responsiveness.JCI insight · 2020Article
- Ventromedial hypothalamic nucleus neuronal subset regulates blood glucose independently of insulin.The Journal of clinical investigation · 2020Article
- MicroRNA-7a overexpression in VMH restores the sympathoadrenal response to hypoglycemia.JCI insight · 2019Article
- Altered Central Nutrient Sensing in Male Mice Lacking Insulin Receptors in Glut4-Expressing Neurons.Endocrinology · 2019Article
- Central Mechanisms of Glucose Sensing and Counterregulation in Defense of Hypoglycemia.Endocrine reviews · 2019Review
- Brain Glucose-Sensing Mechanism and Energy Homeostasis.Molecular neurobiology · 2019Review
- Insulin regulates GLUT4 in the ventromedial hypothalamus to restore the sympathoadrenal response to hypoglycemia in diabetic rats.American journal of physiology. Endocrinology and metabolism · 2018Article
- Autonomic Regulation of Glucose Homeostasis: a Specific Role for Sympathetic Nervous System Activation.Current diabetes reports · 2018Review
- Problem or solution: The strange story of glucagon.Peptides · 2018Review
- Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
objectiveImpaired glucose counterregulation during hypoglycemia is well documented in patients with type 1 diabetes; however, the molecular mechanisms underlying this defect remain uncertain. We reported that the inhibitory neurotransmitter γ-aminobutyric acid (GABA), in a crucial glucose-sensing region within the brain, the ventromedial hypothalamus (VMH), plays an important role in modulating the magnitude of the glucagon and epinephrine responses to hypoglycemia and investigated whether VMH GABAergic tone is altered in diabetes and therefore might contribute to defective counterregulatory responses. RESEARCH DESIGN AND
methodsWe used immunoblots to measure GAD(65) protein (a rate-limiting enzyme in GABA synthesis) and microdialysis to measure extracellular GABA levels in the VMH of two diabetic rat models, the diabetic BB rat and the streptozotocin (STZ)-induced diabetic rat, and compared them with nondiabetic controls.
resultsBoth diabetic rat models exhibited an ~50% increase in GAD(65) protein as well as a twofold increase in VMH GABA levels compared with controls under baseline conditions. Moreover, during hypoglycemia, VMH GABA levels did not change in the diabetic animals, whereas they significantly declined in nondiabetic animals. As expected, glucagon responses were absent and epinephrine responses were attenuated in diabetic rats compared with their nondiabetic control counterparts. The defective counterregulatory response in STZ-diabetic animals was restored to normal with either local blockade of GABA(A) receptors or knockdown of GAD(65) in the VMH.
conclusionsThese data suggest that increased VMH GABAergic inhibition is an important contributor to the absent glucagon response to hypoglycemia and the development of counterregulatory failure in type 1 diabetes.
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Registered trials
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