ArticleThe Journal of clinical investigation2018
Recurrent hypoglycemia inhibits the counterregulatory response by suppressing adrenal activity.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Evaluation of Clinical Metrics for Identifying Defective Physiologic Responses to Hypoglycemia in Long-Standing Type 1 Diabetes.Diabetes technology & therapeutics · 2022Trial
- Trial
- Role of dopamine in the development of impaired counterregulation and impaired awareness of hypoglycemia.Cell reports. Medicine · 2026Article
- Effect of hypoglycemia on the diameter of cerebral vasculature in vivo and cerebral ischemia-reperfusion injury in mice.Experimental neurology · 2026Article
- Clinical and pathophysiological links between hypoglycemia and cardiovascular risk in type 2 diabetes mellitus.Frontiers in clinical diabetes and healthcare · 2026Review
- Article
- The impact of technology on impaired awareness of hypoglycaemia in type 1 diabetes.Therapeutic advances in endocrinology and metabolism · 2025Review
- Role of intestinal glucagon-like peptide-1 in impaired counter-regulatory responses to hypoglycemia.World journal of diabetes · 2024Article
- 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
- Role of the Adrenal Medulla in Hypoglycaemia-Associated Autonomic Failure-A Diabetic Perspective.Metabolites · 2024Review
- Automated Insulin Delivery for Hypoglycemia Avoidance and Glucose Counterregulation in Long-Standing Type 1 Diabetes with Hypoglycemia Unawareness.Diabetes technology & therapeutics · 2023Article
- Synaptotagmin-7 facilitates acetylcholine release in splanchnic nerve-chromaffin cell synapses during nerve activity.Neuroscience letters · 2023Article
- Ghrelin does not impact the blunted counterregulatory response to recurrent hypoglycemia in mice.Frontiers in endocrinology · 2023Article
- Impaired Awareness of Hypoglycemia in Type 1 Diabetes: A Report of An NIDDK Workshop in October 2021.Diabetes care · 2022Review
- Slow but Steady-The Responsiveness of Sympathoadrenal System to a Hypoglycemic Challenge in Ketogenic Diet-Fed Rats.Nutrients · 2021Article
- Integrating the inputs that shape pancreatic islet hormone release.Nature metabolism · 2019Review
- Repetitive hypoglycemia reduces activation of glucose-responsive neurons in C1 and C3 medullary brain regions to subsequent hypoglycemia.American journal of physiology. Endocrinology and metabolism · 2019Article
- Central Mechanisms of Glucose Sensing and Counterregulation in Defense of Hypoglycemia.Endocrine reviews · 2019Review
- Beyond the brain: do peripheral mechanisms develop impaired awareness of hypoglycemia?The Journal of clinical investigation · 2018Article
- USE OF A CONTINUOUS GLUCOSE MONITOR FOR PREOPERATIVE MONITORING AND TREATMENT OF HYPOGLYCEMIA IN A CASE OF PANCREATIC NEUROENDOCRINE TUMOR.AACE clinical case reportsArticle
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Hypoglycemia activates the counterregulatory response (CRR), a neural-endocrine reflex that restores euglycemia. Although effective if occasionally activated, repeated induction of the CRR leads to a decline in responsiveness and prolonged exposure to hypoglycemia. The mechanism underlying this impairment is not known. We found that the reduction in epinephrine release that characterizes a suppressed CRR involves a long-lasting form of sympatho-adrenal synaptic plasticity. Using optogenetically evoked catecholamine release, we show that recurrent hypoglycemia reduced the secretory capacity of mouse adrenal chromaffin cells. Single activation of the CRR increased the adrenal levels of tyrosine hydroxylase (TH), the rate-limiting enzyme for catecholamine synthesis, but this was prevented by repeated activation. In contrast, the level of neuropeptide Y (NPY), an adrenal cotransmitter, remained elevated after recurrent hypoglycemia. Inhibition of NPY or Y1 signaling, either transgenically or pharmacologically, prevented the attenuation of both TH expression and epinephrine release. These results indicate that impairment of the CRR involves suppressed activity at the adrenal level. Interfering with the peripheral NPY-dependent negative feedback loop may provide a way to avoid the pathophysiological consequences of recurrent hypoglycemia which are common in the diabetic state.
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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.