Linked Life Data

17185376

Source:http://linkedlifedata.com/resource/pubmed/id/17185376

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-2-16
pubmed:abstractText
Antecedent hypoglycemia blunts counterregulatory responses that normally restore glycemia, a phenomenon known as hypoglycemia-associated autonomic failure (HAAF). The mechanisms leading to impaired counterregulatory responses are largely unknown. Hypothalamic AMP-activated protein kinase (AMPK) acts as a glucose sensor. To determine whether failure to activate AMPK could be involved in the etiology of HAAF, we developed a model of HAAF using repetitive intracerebroventricular (icv) injection of 2-deoxy-D-glucose (2DG) resulting in transient neuroglucopenia in normal rats. Ten minutes after a single icv injection of 2DG, both alpha1- and alpha2-AMPK activities were increased 30-50% in arcuate and ventromedial/dorsomedial hypothalamus but not in other hypothalamic regions, hindbrain, or cortex. Increased AMPK activity persisted in arcuate hypothalamus at 60 min after 2DG injection when serum glucagon and corticosterone levels were increased 2.5- to 3.4-fold. When 2DG was injected icv daily for 4 d, hypothalamic alpha1- and alpha2-AMPK responses were markedly blunted in arcuate hypothalamus, and alpha1-AMPK was also blunted in mediobasal hypothalamus 10 min after 2DG on d 4. Both AMPK isoforms were activated normally in arcuate hypothalamus at 60 min. Counterregulatory hormone responses were impaired by recurrent neuroglucopenia and were partially restored by icv injection of 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside, an AMPK activator, before 2DG. Glycogen content increased 2-fold in hypothalamus after recurrent neuroglucopenia, suggesting that glycogen supercompensation could be involved in down-regulating the AMPK glucose-sensing pathway in HAAF. Thus, activation of hypothalamic AMPK may be important for the full counterregulatory hormone response to neuroglucopenia. Furthermore, impaired or delayed AMPK activation in specific hypothalamic regions may play a critical role in the etiology of HAAF.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
148
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1367-75
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17185376-AMP-Activated Protein Kinases, pubmed-meshheading:17185376-Aminoimidazole Carboxamide, pubmed-meshheading:17185376-Animals, pubmed-meshheading:17185376-Brain, pubmed-meshheading:17185376-Brain Chemistry, pubmed-meshheading:17185376-Deoxyglucose, pubmed-meshheading:17185376-Eating, pubmed-meshheading:17185376-Glucose, pubmed-meshheading:17185376-Glycogen, pubmed-meshheading:17185376-Hypoglycemia, pubmed-meshheading:17185376-Hypothalamus, pubmed-meshheading:17185376-Male, pubmed-meshheading:17185376-Multienzyme Complexes, pubmed-meshheading:17185376-Neurosecretory Systems, pubmed-meshheading:17185376-Protein-Serine-Threonine Kinases, pubmed-meshheading:17185376-Rats, pubmed-meshheading:17185376-Rats, Sprague-Dawley, pubmed-meshheading:17185376-Recurrence, pubmed-meshheading:17185376-Ribonucleotides
pubmed:year
2007
pubmed:articleTitle
Role of hypothalamic adenosine 5'-monophosphate-activated protein kinase in the impaired counterregulatory response induced by repetitive neuroglucopenia.
pubmed:affiliation
Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, 99 Brookline Avenue, Boston, MA 02215, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural