RGD Reference Report - Increased lipogenic capacity of the islets of obese rats: a role in the pathogenesis of NIDDM. - Rat Genome Database

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Increased lipogenic capacity of the islets of obese rats: a role in the pathogenesis of NIDDM.

Authors: Lee, Y  Hirose, H  Zhou, YT  Esser, V  McGarry, JD  Unger, RH 
Citation: Lee Y, etal., Diabetes. 1997 Mar;46(3):408-13.
RGD ID: 2313659
Pubmed: PMID:9032096   (View Abstract at PubMed)

The onset of NIDDM in obese Zucker diabetic fatty (fa/fa) rats is preceded by a striking increase in the plasma levels of free fatty acids (FFAs) and by a sixfold rise in triglyceride content in the pancreatic islets. The latter finding provides clear evidence of elevated tissue levels of long-chain fatty acyl CoA, which can impair beta-cell cell function. To determine if the triglyceride accumulation is entirely the passive consequence of high plasma FFA levels or if prediabetic islets have an increased lipogenic capacity that might predispose to NIDDM, the metabolism of long-chain fatty acids was compared in islets of obese prediabetic and nonprediabetic Zucker diabetic fatty (ZDF) rats and of lean Wistar and lean ZDF rats. When cultured in 1 or 2 mmol/l FFA, islets of both female and male obese rats accumulated, respectively, 7 and 15 times as much triglyceride as islets from lean rats exposed to identical FFA concentrations. The esterification of [14C]palmitate and 9,10-[3H]palmitate was increased in islets of male obese rats and could not be accounted for by defective oxidation of 9,10-[3H]-palmitate. Glycerol-3-PO4 acyl-transferase (GPAT) activity was 12 times that of controls. The mRNA of GPAT was increased in islets of obese rats. We conclude that, in the presence of comparable elevations in FFA concentrations, the islets of obese prediabetic rats have a higher lipogenic capacity than controls. This could be a factor in their high risk of diabetes.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GPAMHumanobesity  ISOGpam (Rattus norvegicus)mRNA:increased expression:pancreatic isletRGD 
GpamRatobesity  IEP mRNA:increased expression:pancreatic isletRGD 
GpamMouseobesity  ISOGpam (Rattus norvegicus)mRNA:increased expression:pancreatic isletRGD 

Objects Annotated

Genes (Rattus norvegicus)
Gpam  (glycerol-3-phosphate acyltransferase, mitochondrial)

Genes (Mus musculus)
Gpam  (glycerol-3-phosphate acyltransferase, mitochondrial)

Genes (Homo sapiens)
GPAM  (glycerol-3-phosphate acyltransferase, mitochondrial)


Additional Information