Linked Life Data

11359864

Source:http://linkedlifedata.com/resource/pubmed/id/11359864

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-5-21
pubmed:abstractText
To assess the dominance between hypoinsulinemia and hypoleptinemia as factors in the development of hyperphagia in streptozotocin (STZ)-induced diabetes mellitus (STZ-DM) rodents with respect to hormone-neuropeptide interactions, changes in gene expression of agouti gene-related protein (AGRP) in the arcuate nucleus of the hypothalamus were investigated using STZ-DM rats, fasting Zucker fa/fa rats and STZ-DM agouti (STZ-DM A(y)/a) mice. AGRP mRNA and neuropeptide Y mRNA were both significantly up-regulated in STZ-DM rats, which are associated with body weight loss, hyperglycemia, hypoinsulinemia and hypoleptinemia. We proceeded to analyze whether insulin or leptin played the greater role in the regulation of AGRP using Zucker fa/fa rats. The AGRP mRNA did not differ significantly between fasted fa/fa rats, which have both leptin-insensitivity and hypoinsulinemia, and fed Zuckers, which have leptin-insensitivity and hyperinsulinemia. We further found that up-regulation of AGRP expression was normalized by infusion of leptin into the third cerebroventricle (i3vt), but not by i3vt infusion of insulin, although up-regulation of AGRP was partially corrected by systemic insulin infusion. The latter finding supports hypoleptinemia as a key-modulator of STZ-DM-induced hyperphagia because systemic insulin infusion, at least partially, restored hypoleptinemia through its acceleration of fat deposition, as demonstrated by the partial recovery of lost body weight. After STZ-DM induction, A(y)/a mice whose melanocortin-4 receptor (MC4-R) was blocked by ectopic expression of agouti protein additionally accelerated hyperphagia and up-regulated AGRP mRNA, implying that the mechanism is triggered by a leptin deficit rather than by the main action of the message through MC4-R. Hypoleptinemia, but not hypoinsulinemia per se, thus develops hyperphagia in STZ-DM rodents. These results are very much in line with evidence that hypothalamic neuropeptides are potently regulated by leptin as downstream targets of its actions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
77
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
993-1000
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:11359864-Agouti Signaling Protein, pubmed-meshheading:11359864-Animals, pubmed-meshheading:11359864-Blood Glucose, pubmed-meshheading:11359864-Cerebral Ventricles, pubmed-meshheading:11359864-Diabetes Mellitus, Experimental, pubmed-meshheading:11359864-Feeding Behavior, pubmed-meshheading:11359864-Food Deprivation, pubmed-meshheading:11359864-Gene Expression Regulation, pubmed-meshheading:11359864-Hyperphagia, pubmed-meshheading:11359864-Hypothalamus, pubmed-meshheading:11359864-Infusions, Parenteral, pubmed-meshheading:11359864-Insulin, pubmed-meshheading:11359864-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:11359864-Leptin, pubmed-meshheading:11359864-Male, pubmed-meshheading:11359864-Neuropeptide Y, pubmed-meshheading:11359864-Protein Precursors, pubmed-meshheading:11359864-Proteins, pubmed-meshheading:11359864-RNA, Messenger, pubmed-meshheading:11359864-Rats, pubmed-meshheading:11359864-Rats, Wistar, pubmed-meshheading:11359864-Rats, Zucker, pubmed-meshheading:11359864-Transcription, Genetic, pubmed-meshheading:11359864-Weight Loss
pubmed:year
2001
pubmed:articleTitle
Hypoleptinemia, but not hypoinsulinemia, induces hyperphagia in streptozotocin-induced diabetic rats.
pubmed:affiliation
Department of Internal Medicine I, School of Medicine, Oita Medical University, Oita, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't