Rat neonatal beta cells lack the specialised metabolic phenotype of mature beta cells.
OBJECTIVE
Fetal and neonatal beta cells have poor glucose-induced insulin secretion and only gain robust glucose responsiveness several weeks after birth. We hypothesise that this unresponsiveness is due to a generalised immaturity of the metabolic pathways normally found in beta cells rather than to a specific defect.


METHODS
Using laser-capture microdissection we excised beta cell-enriched cores of pancreatic islets from day 1 (P1) neonatal and young adult Sprague-Dawley rats in order to compare their gene-expression profiles using Affymetrix U34A microarrays (neonatal, n = 4; adult, n = 3).


RESULTS
Using dChip software for analysis, 217 probe sets for genes/38 expressed sequence tags (ESTs) were significantly higher and 345 probe sets for genes/33 ESTs significantly lower in beta cell-enriched cores of neonatal islets compared with those of adult islets. Among the genes lower in the neonatal beta cells were key metabolic genes including mitochondrial shuttles (malate dehydrogenase, glycerol-3-phosphate dehydrogenase and glutamate oxalacetate transaminase), pyruvate carboxylase and carnitine palmitoyl transferase 2. Differential expression of these enzyme genes was confirmed by quantitative PCR on RNA from isolated neonatal (P2 until P28) and adult islets and with immunostaining of pancreas. Even by 28 days of age some of these genes were still expressed at lower levels than in adults.


CONCLUSIONS
The lack of glucose responsiveness in neonatal islets is likely to be due to a generalised immaturity of the metabolic specialisation of pancreatic beta cells.
Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.
A
A
Jermendy
E
E
Toschi
T
T
Aye
A
A
Koh
C
C
Aguayo-Mazzucato
A
A
Sharma
G C
GC
Weir
D
D
Sgroi
S
S
Bonner-Weir
D000818:Animals; D000831:Animals, Newborn; D001219:Aspartate Aminotransferases / Q000235:genetics; D020224:Expressed Sequence Tags; D005260:Female; D005993:Glycerolphosphate Dehydrogenase / Q000235:genetics; D066298:In Vitro Techniques; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000235:genetics; D008297:Male; D042282:Microdissection; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005993:Glycerolphosphate Dehydrogenase; D008291:Malate Dehydrogenase; D001219:Aspartate Aminotransferases
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