Linked Life Data

12147706

Source:http://linkedlifedata.com/resource/pubmed/id/12147706

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
2002-10-15
pubmed:abstractText
The beta-cell biochemical mechanisms that account for the compensatory hyperfunction with insulin resistance (so-called beta-cell adaptation) are unknown. We investigated glucose metabolism in isolated islets from 10-12-week-old Zucker fatty (ZF) and Zucker lean (ZL) rats (results expressed per mg/islet of protein). ZF rats were obese, hyperlipidemic, and normoglycemic. They had a 3.8-fold increased beta-cell mass along with 3-10-fold increases in insulin secretion to various stimuli during pancreas perfusion despite insulin content per milligram of beta-cells being only one-third that of ZL rats. Islet glucose metabolism (utilization and oxidation) was 1.5-2-fold increased in the ZF islets despite pyruvate dehydrogenase activity being 30% lowered compared with the ZL islets. The reason was increased flux through pyruvate carboxylase (PC) and the malate-pyruvate and citrate-pyruvate shuttles based on the following observations (% ZL islets): increased V(max) of PC (160%), malate dehydrogenase (170%), and malic enzyme (275%); elevated concentrations of oxaloacetate (150%), malate (250%), citrate (140%), and pyruvate (250%); and 2-fold increased release of malate from isolated mitochondria. Inhibition of PC by 5 mm phenylacetic acid markedly lowered glucose-induced insulin secretion in ZF and ZL islets. Thus, our results suggest that PC and the pyruvate shuttles are increased in ZF islets, and this accounts for glucose mitochondrial metabolism being increased when pyruvate dehydrogenase activity is reduced. As the anaplerosis pathways are implicated in glucose-induced insulin secretion and the synthesis of glucose-derived lipid and amino acids, our results highlight the potential importance of PC and the anaplerosis pathways in the enhanced insulin secretion and beta-cell growth that characterize beta-cell adaptation to insulin resistance.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
39163-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12147706-Animals, pubmed-meshheading:12147706-Body Weight, pubmed-meshheading:12147706-Citric Acid, pubmed-meshheading:12147706-Dose-Response Relationship, Drug, pubmed-meshheading:12147706-Glucose, pubmed-meshheading:12147706-Glycerol, pubmed-meshheading:12147706-Insulin Resistance, pubmed-meshheading:12147706-Islets of Langerhans, pubmed-meshheading:12147706-Kinetics, pubmed-meshheading:12147706-Malate Dehydrogenase, pubmed-meshheading:12147706-Malates, pubmed-meshheading:12147706-Mitochondria, pubmed-meshheading:12147706-Oxaloacetate, pubmed-meshheading:12147706-Pancreas, pubmed-meshheading:12147706-Perfusion, pubmed-meshheading:12147706-Phenylacetates, pubmed-meshheading:12147706-Pyruvate Carboxylase, pubmed-meshheading:12147706-Pyruvic Acid, pubmed-meshheading:12147706-Rats, pubmed-meshheading:12147706-Rats, Zucker, pubmed-meshheading:12147706-Time Factors
pubmed:year
2002
pubmed:articleTitle
beta-Cell adaptation to insulin resistance. Increased pyruvate carboxylase and malate-pyruvate shuttle activity in islets of nondiabetic Zucker fatty rats.
pubmed:affiliation
Division of Endocrinology, Diabetes, and Metabolism, University of Vermont, Burlington, Vermont 05405, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't