RGD Reference Report - Role of NADH shuttles in glucose-induced insulin secretion from fetal beta-cells. - Rat Genome Database

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Role of NADH shuttles in glucose-induced insulin secretion from fetal beta-cells.

Authors: Tan, C  Tuch, BE  Tu, J  Brown, SA 
Citation: Tan C, etal., Diabetes. 2002 Oct;51(10):2989-96.
RGD ID: 2303499
Pubmed: PMID:12351438   (View Abstract at PubMed)

The NADH shuttle system, which transports the substrate for oxidative metabolism directly from the cytosol to the mitochondrial electron transport chain, has been shown to be essential for glucose-induced activation of mitochondrial metabolism and insulin secretion in adult beta-cells. We examined the role of these shuttles in the fetal beta-cell, which is immature in being unable to secrete insulin in response to glucose. The activity and concentration of the two key enzymes of the NADH shuttles, mitochondrial glycerol phosphate dehydrogenase (mGPDH) and mitochondrial malate dehydrogenase (mMDH), were eight- and threefold lower, respectively, in fetal compared with adult rat islets. Likewise, mGPDH and mMDH activity was fivefold lower in islet-like cell clusters (ICCs) and sevenfold lower in purified beta-cells compared with adult islets in the pig. The low level of enzyme activity was a result of low gene expression of the mitochondrial enzymes in the fetal beta-cells. Increasing NADH shuttle activity by transduction of fetal rat islets with mGPDH cDNA enabled the fetal islets to secrete insulin when stimulated with glucose. We concluded that the immaturity of the NADH shuttles contributes to the inability of fetal beta-cells to secrete insulin in response to glucose.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Gpd1Ratglycerol-3-phosphate metabolic process  IDA  RGD 
Gpd2Ratglycerol-3-phosphate metabolic process  IDA  RGD 
Mdh1Ratmalate metabolic process  IDA  RGD 
Mdh2Ratmalate metabolic process  IDA  RGD 
Gpd1RatNADH metabolic process  IDA  RGD 
Gpd2RatNADH metabolic process  IDA  RGD 
Mdh1RatNADH metabolic process  IDA  RGD 
Mdh2RatNADH metabolic process  IDA  RGD 

Molecular Function

  

Objects Annotated

Genes (Rattus norvegicus)
Gpd1  (glycerol-3-phosphate dehydrogenase 1)
Gpd2  (glycerol-3-phosphate dehydrogenase 2)
Mdh1  (malate dehydrogenase 1)
Mdh2  (malate dehydrogenase 2)


Additional Information