PXD001577

PXD001577 is an original dataset announced via ProteomeXchange.

Title	Functional characteristics of neonatal rat beta cells With distinct markers
Description	Neonatal beta cells are considered developmentally immature and hence less glucose-responsive. To study the acquisition of mature glucose-responsiveness, we compared glucose-regulated redox state, insulin synthesis and secretion of beta cells purified from neonatal or 10-weeks old rats to their transcriptomes and proteomes measured by oligonucleotide and LC-MS/MS profiling. Lower glucose-responsiveness of neonatal beta cells was explained by two distinct properties: higher activity at low glucose and lower activity at high glucose. Basal hyperactivity was associated with higher NAD(P)H, a higher fraction of neonatal beta cells actively incorporating 3H-Tyrosine, and persistently increased insulin secretion below 5 mM glucose. Neonatal beta cells lacked the steep glucose-responsive NAD(P)H rise between 5-10 mM glucose characteristic for adult beta cells, and accumulated less NAD(P)H at high glucose. They had 2-fold lower expression of malate/aspartate-NADH shuttle and most glycolytic enzymes. Genome-wide profiling situated neonatal beta cells at a developmental crossroad: they showed advanced endocrine differentiation when specifically analyzed for their mRNA/protein level of classical neuroendocrine markers. On the other hand, discrete neonatal beta cell subpopulations still expressed mRNAs/proteins typical for developing/proliferating tissues. One example, Delta-like 1 homolog (DLK1) was used to investigate if neonatal beta cells with basal hyperactivity corresponded to a more immature subset with high DLK1, but no association was found. In conclusion, the current study supports the importance of glycolytic NADH-shuttling in stimulus-function coupling, presents basal hyperactivity as novel property of neonatal beta cells, and provides potential markers to recognize intercellular developmental differences in the endocrine pancreas.
HostingRepository	PRIDE
AnnounceDate	2014-12-12
AnnouncementXML	Submission_2014-12-12_09:00:47.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gertjan Kramer
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Synapt G2 MS

Revision	Datetime	Status	ChangeLog Entry
0	2014-12-05 08:54:09	ID requested
⏵ 1	2014-12-12 09:00:49	announced

Martens GA, Mott, é E, Kramer G, Stang, é G, Gaarn LW, Hellemans K, Nielsen JH, Aerts JM, Ling Z, Pipeleers D, cells with distinct markers. J Mol Endocrinol, 52(1):11-28(2014) [pubmed]

curator keyword: Biological

submitter keyword: Rat, Pancreas, Diabetes, LCMSE, label free quantitation

J.M.F.G Aerts
contact affiliation	Clinical proteomics facility, Medical Biochemistry, Academic Medical Center, University of Amstedam
contact email	j.m.aerts@amc.uva.nl
lab head
Gertjan Kramer
contact affiliation	Proteomics Unit
contact email	gertjan.kramer@embl.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001577
     1. Label: PRIDE project
     2. Name: Functional characteristics of neonatal rat beta cells With distinct markers