title: Effect of insulin-induced hypoglycaemia on the central nervous system: evidence from experimental studies.
abstract: Insulin-induced hypoglycaemia (IIH) is a major acute complication in type 1 as well as in type 2 diabetes, particularly during intensive insulin therapy. The brain plays a central role in the counter-regulatory response by eliciting parasympathetic and sympathetic hormone responses to restore normoglycaemia. Brain glucose concentrations, being approximately 15-20% of the blood glucose concentration in humans, are rigorously maintained during hypoglycaemia through adaptions such as increased cerebral glucose transport, decreased cerebral glucose utilisation and, possibly, by using central nervous system glycogen as a glucose reserve. However, during sustained hypoglycaemia, the brain cannot maintain a sufficient glucose influx and, as the cerebral hypoglycaemia becomes severe, electroencephalogram changes, oxidative stress and regional neuronal death ensues. With particular focus on evidence from experimental studies on nondiabetic IIH, this review outlines the central mechanisms behind the counter-regulatory response to IIH, as well as cerebral adaption to avoid sequelae of cerebral neuroglycopaenia, including seizures and coma.
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Diabetes Toxicology and Safety Pharmacology, Novo Nordisk A/S, Maaloev, Denmark.
authors.forename: V F H
authors.initials: VF
authors.lastname: Jensen
authors.forename: I B
authors.initials: IB
authors.lastname: Bøgh
authors.forename: J
authors.initials: J
authors.lastname: Lykkesfeldt
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007003:Hypoglycemia / Q000139:chemically induced* / Q000378:metabolism; D007328:Insulin / Q000009:adverse effects* / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D007328:Insulin; D005947:Glucose
keywords: binding proteins; glucose transporters; insulin; membrane; receptors