Exendin 4 up-regulates expression of @entity5908 and hastens differentiation and maturation of XXXX fetal pancreatic cells.

@entity1 @entity5908 @entity2690 @entity35 @entity413
In addition to stimulating insulin secretion, glucagon-like peptide and its long-acting analog exendin 4 have been reported to increase beta-cell mass by both differentiation/neogenesis of precursor cells and enhanced replication of existing beta-cells. Here, we investigated the effect of exendin 4 in the growth and differentiation of beta-cells from undifferentiated precursors in islet-like cell clusters (ICCs) derived from @entity1 fetal pancreases. Our results show that the addition of exendin 4 to the culture media stimulates @entity5908 expression in ICCs as shown by immunofluorescence staining. The up-regulation of @entity5908 was not accompanied by changes in insulin expression because we did not find a significant difference in the number of insulin-positive cells in the exendin 4-treated ICCs, compared with controls. We also tested the effects of exendin 4 in the @entity413 -induced insulin secretion of @entity1 ICCs transplanted under the kidney capsule of athymic @entity35 . In the exendin 4-treated @entity35 (given ip during 10 d) 8 wk after the beginning of the treatment, insulin was released in response to @entity413 as detected by the measurement of circulating @entity1 @entity2690 . In control (saline-treated) @entity35 , the basal levels of @entity1 @entity2690 did not change significantly after @entity413 stimulation. Thus, exendin 4 induces functional maturation of fetal beta-cells in response to @entity413 . In these @entity35 , serial sections of the kidney-bearing grafts were examined histologically for insulin containing cells. We found a significant increase in beta-cell number, compared with the control @entity35 . Overall, these results show that in vivo exendin 4 causes growth and differentiation of @entity1 fetal beta-cells from undifferentiated precursor cells. It also accelerates the functional maturation of fetal beta-cells as evidenced by their @entity413 -stimulated insulin secretion.
