Effect of Antecedent Glucose Control on Cerebral Function During Hypoglycemia

Amiel, Stephanie A.; Pottinger, Richard C; Archibald, Helen; Chusney, Gary; Cunnah, D.; Prior, Pamela F.; Gale, E. A. M.

doi:10.2337/diacare.14.2.109

Cited by 103 publications

(68 citation statements)

References 20 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Yet, maintaining a constant glucose concentration in brain tissue is important to the preservation of neuronal functioning. Several studies have shown characteristic electroencephalogram changes during hypoglycemia (plasma glucose Ͻ2.0 mmol/l) in both type 1 diabetic and healthy subjects (33,34). Hyperglycemia with concomitantly increased glucose concentration in brain tissue accelerates ischemic damage and worsens the outcome after ischemic stroke (35).…”

Section: Discussionmentioning

confidence: 99%

Glucagon-Like Peptide-1 Inhibits Blood-Brain Glucose Transfer in Humans

et al. 2008

View full text Add to dashboard Cite

OBJECTIVE-Glucagon-like peptide-1 (GLP-1) has many effects on glucose homeostasis, and GLP-1 receptors are broadly represented in many tissues including the brain. Recent research in rodents suggests a protective effect of GLP-1 on brain tissue. The mechanism is unknown. We therefore tested whether these neuroprotective effects could relate to changes of glucose transport and consumption.RESEARCH DESIGN AND METHODS-We studied 10 healthy men in a randomized, double-blinded, placebo-controlled cross-over experiment. We used positron emission tomography to determine the acute insulin-independent effect of GLP-1 on unidirectional glucose transport into the brain during a pituitarypancreatic normoglycemic (plasma glucose ϳ4.5 mmol/l) clamp with 18-fluoro-deoxy-glucose as tracer.RESULTS-On average, GLP-1 reduced cerebral glucose transport by 27% in total cerebral gray matter (P ϭ 0.05) and by 25-30% in individual gray matter regions (P ϭ 0.02-0.06). The same regions revealed a uniform trend toward similarly reduced cerebral glucose metabolism. Consequently, the intracerebral glucose concentration remained constant in all regions, with and without GLP-1. CONCLUSIONS-We have demonstrated that a hormone involved in postprandial glucose regulation also limits glucose delivery to brain tissue and hence provides a possible regulatory mechanism for the link between plasma glucose and brain glucose. Because GLP-1 reduces glucose uptake across the intact blood-brain barrier at normal glycemia, GLP-1 may also protect the brain by limiting intracerebral glucose fluctuation when plasma glucose is increased. Diabetes 57:325-331, 2008 G lucagon-like peptide-1 (GLP-1) is an incretin hormone with several beneficial effects on glucose homeostasis. GLP-1 is not solely produced by the entero-endocrine L-cells in the gut but also in the brain by neurons in the nucleus of the tractus solitarius and thus functions as a neuropeptide (1). It stimulates insulin secretion and inhibits glucagon secretion in the presence of glucose, inhibits gastric emptying, and reduces appetite and food intake (2,3). Furthermore, it acts as a ␤-cell growth factor by stimulating ␤-cell proliferation and islet neogenesis and by reducing ␤-cell apoptosis (4). The glucose dependency of GLP-1 action on insulin and glucagon secretion results in a low risk of hypoglycemic episodes (5). These effects make GLP-1 attractive as an anti-diabetes medication, and several studies prove the beneficial effect on glucose homeostasis in the type 2 diabetic patient (6,7).Although GLP-1 receptors (GLP-1Rs) are predominantly located on the ␤-, ␦-, and presumably ␣-cells of the pancreas, receptors in other tissues may mediate GLP-1's effects outside the pancreas (8,9), where gastric emptying and appetite are well-known targets, as are other tissues including heart, kidney, and lungs (8). GLP-1R expression has been demonstrated in human brain (10), where receptors are particularly abundant in the paraventricular nucleus and the arcuate nucleus in the hypothalamus (11). Infusion of GL...

show abstract

Section: Discussionmentioning

confidence: 99%

Glucagon-Like Peptide-1 Inhibits Blood-Brain Glucose Transfer in Humans

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Plasma catecholamine concentrations were determined by high-performance liquid chromatography [12] and plasma concentrations of free insulin and C peptide were measured by standard radioimmunoassay procedures [13]. A fluorimetric method was used to measure blood lactate, intermediary metabolites [14], and free fatty acids [15].…”

Section: Methodsmentioning

confidence: 99%

Brain function rescue effect of lactate following hypoglycaemia is not an adaptation process in both normal and Type I diabetic subjects

et al. 2000

View full text Add to dashboard Cite

Patients with Type I (insulin-dependent) diabetes mellitus receiving intensified insulin therapy and having strict metabolic control are exposed to the risk of recurrent episodes of hypoglycaemia [1]. Defective counterregulatory and symptomatic responses to hypoglycaemia are responsible for reduced awareness of hypoglycaemia [2] which can aggravate cerebral dysfunction by increasing the occurrence and severity Diabetologia (2000) 43: 733±741Brain function rescue effect of lactate following hypoglycaemia is not an adaptation process in both normal and Type I diabetic subjects Abstract Aims/hypothesis. We have previously shown that lactate protects brain function during insulin-induced hypoglycaemia. An adaptation process could, however, not be excluded because the blood lactate increase preceded hypoglycaemia. Methods. We studied seven healthy volunteers and seven patients with Type I (insulin-dependent) diabetes mellitus with a hyperinsulinaemic (1.5 mUḱ g ±1´m in ±1 ) stepwise hypoglycaemic clamp (4.8 to 3.6, 3.0 and 2.8 mmo/l) with and without Na-lactate infusion (30 mmol´kg ±1´m in ±1 ) given after initiation of hypoglycaemic symptoms. Results. The glucose threshold for epinephrine response was similar (control subjects 3.2 0.1 vs 3.2 0.1, diabetic patients = 3.5 0.1 vs 3.5 0.1 mmol/l) in both studies. The magnitude of the response was, however, blunted by lactate infusion (AUC; control subjects 65 28 vs 314 55 nmol/l/180 min, zenith = 2.6 0.5 vs 4.8 0.7 nmol/l, p < 0.05; diabetic patients = 102 14 vs 205 40 nmol/l/180 min, zenith = 1.4 0.4 vs 3.2 0.3 nmol/l, p < 0.01). The glucose threshold for symptoms was also similar (C = autonomic 3.0 0.1 vs 3.0 0.1, neuroglycopenic = 2.8 0.1 vs 2.9 0.1 mmol/l, D = autonomic 3.2 0.1 vs 3.2 0.1, neuroglycopenic 3.1 0.1 vs

show abstract

“…As the blood glucose fall progresses, an intensification of the autonomic response produces a symptom complex that an individual can learn to recognize as a warning that he or she should eat. Only if these initial defence mechanisms fail and plasma glucose falls below 3 mmoYl do we start to see evidence of cognitive dysfunction and a further decline in circulating plasma glucose is required to detect changes in the EEG (Amiel et al 1991b). Current thinking is that most, if not all, of these responses are triggered by a fall in cerebral glucose metabolism (Biggers et al 1989).…”

mentioning

confidence: 99%

Organ fuel selection: brain

Amiel

1995

Proc. Nutr. Soc.

View full text Add to dashboard Cite

Le silection mdtabolique au niveau du cerveau R E S U M ELe cerveau normalement doit obligatoirement consommer du glucose, mais il a le potentiel enzymatique pour mktaboliser d'autres substrats. Une chute du glucose apportk au cerveau par sa circulation, comme dans I'hypoglyctmie (faible concentration de glucose dans le sang), est suivie par une chute du taux metabolique ckrkbral en glucose, et par le dkclenchement des rkponses hormonales symptomatiques (qui agissent pour rktablir le glucose du sang), ainsi que par une perte de conscience. Le jeQne, qui augmente les corps cktoniques circulants, rend le sujet humain relativement rksistant aux sympt8mes et B la perte de conscience de l'hypoglyckmie. Owen ef al. (1967) ont utilisk les mesures des corps cCtoniques dans la circulation cCrCbrale pour montrer que le cerveau humain pourrait utiliser des corps cktoniques apres un jeiine prolongk, mais la nkcessitt d'une pkriode d'adaptation pour que le cerveau mttabolise les corps cCtoniques a Ctk remise question dans des ktudes sur I'animal dans lesquelles le cerveau du rongeur in vivo absorbait les corps cktoniques pendant le jeQne ou une perfusion de corps cktoniques B l'ktat nourri. La perfusion de corps cktoniques chez l'homme retarde l'apparition de ces reponses hormonales B I'hypoglyckmie induite par l'insuline, rCponses dont on pense qu'elles sont dkclenchkes dans le cerveau, ce qui laisse B penser que le cerveau de l'homme peut mktaboliser les corps cktoniques s'ils sont apportks au cours de l'hypoglyckmie aigue. L'abaissement du niveau des corps cktoniques circulants au cours de l'hypoglyckmie ne semble cependant pas augmenter le risque de dysfonction de la conscience. Le lactate est un autre substrat potentiel pour le mktabolisme ckrkbral. Le cerveau du chien diabttique peut consommer du lactate pendant l'hypoglyckmie. L'infusion de lactate chez I'homme retarde I'apparition des rkponses hormonales et les altkrations de la conscience dans l'hypoglyckmie, ce qui laisse h penser que le cerveau de l'homme peut aussi utiliser le lactate pour maintenir le mktabolisme et les fonctions dans 1'hypoglycCmie. D'autres substrats non glucidiques restent encore B tester. L'absorption d'acides aminks semble &re sous le contr8le des concentrations relatives des acides aminks B chaine ramifike ou neutres dans le sang. I1 semblerait que tandis que le cerveau utilise habituellement du glucose comme substrat knergktique pour son mttabolisme et sa fonction, lorsque le glucose manque, il peut Cgalement utiliser des corps cktoniques et du lactate (et peut-Ctre d'autres substrats).

show abstract

Effect of Antecedent Glucose Control on Cerebral Function During Hypoglycemia

Cited by 103 publications

References 20 publications

Glucagon-Like Peptide-1 Inhibits Blood-Brain Glucose Transfer in Humans

Glucagon-Like Peptide-1 Inhibits Blood-Brain Glucose Transfer in Humans

Brain function rescue effect of lactate following hypoglycaemia is not an adaptation process in both normal and Type I diabetic subjects

Organ fuel selection: brain

Contact Info

Product

Resources

About