Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
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Query: UNIPROT:P61278 (
somatostatin
)
22,083
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Extracellular signals that guide pancreas cell development are not well characterized. In an in vitro culture system of dissociated pancreas cells from the E15.5 mouse fetus we show that, in the presence of the extracellular matrix protein laminin-1, bone morphogenetic proteins (BMPs-4, -5 and -6) promote the development of cystic epithelial colonies. Transforming growth factor beta1 (TGF-beta1) and
activin A
antagonise this effect of BMP-6 and inhibit colony formation. Histological analysis revealed that the colonies are composed of E-cadherin-positive epithelial cells, which in localised areas are insulin positive. The colonies also contain occasional glucagon-positive cells, but no
somatostatin
- or alpha-amylase-positive cells. These findings indicate that members of the TGF-beta superfamily regulate pancreas epithelial cell development and can promote the formation of islet-like structures in vitro.
...
PMID:Bone morphogenetic proteins promote development of fetal pancreas epithelial colonies containing insulin-positive cells. 1186 31
Activin A and betacellulin (BTC) are thought to regulate differentiation of pancreatic beta-cells during development and regeneration of beta-cells in adults. In the present study, we used neonatal rats treated with streptozotocin (STZ) to investigate the effects of
activin A
and BTC on regeneration of pancreatic beta-cells. One-day-old Sprague-Dawley rats were injected with STZ (85 micro g/g) and then administered for 7 days with
activin A
and/or BTC. Treatment with
activin A
and BTC significantly reduced the plasma glucose concentration and the plasma glucose response to intraperitoneal glucose loading. The pancreatic insulin content and beta-cell mass in rats treated with
activin A
and BTC were significantly increased compared with the control group on day 8 and at 2 months. Treatment with
activin A
and BTC significantly increased the DNA synthesis in preexisting beta-cells, ductal cells, and delta-cells. The number of islet cell-like clusters (ICCs) and islets was significantly increased by treatment with
activin A
and BTC. In addition, the number of insulin/
somatostatin
-positive cells and pancreatic duodenal homeobox-1/
somatostatin
-positive cells was significantly increased. These results indicate that, in neonatal STZ-treated rats, a combination of
activin A
and BTC promoted regeneration of pancreatic beta-cells and improved glucose metabolism in adults.
...
PMID:Activin A and betacellulin: effect on regeneration of pancreatic beta-cells in neonatal streptozotocin-treated rats. 1498 44
Recent success in pancreatic islet transplantation has energized the field to discover an alternative source of stem cells with differentiation potential to beta cells. Generation of glucose-responsive, insulin-producing beta cells from self-renewing, pluripotent human ESCs (hESCs) has immense potential for diabetes treatment. We report here the development of a novel serum-free protocol to generate insulin-producing islet-like clusters (ILCs) from hESCs grown under feeder-free conditions. In this 36-day protocol, hESCs were treated with sodium butyrate and
activin A
to generate definitive endoderm coexpressing CXCR4 and Sox17, and CXCR4 and Foxa2. The endoderm population was then converted into cellular aggregates and further differentiated to Pdx1-expressing pancreatic endoderm in the presence of epidermal growth factor, basic fibroblast growth factor, and noggin. Soon thereafter, expression of Ptf1a and Ngn3 was detected, indicative of further pancreatic differentiation. The aggregates were finally matured in the presence of insulin-like growth factor II and nicotinamide. The temporal pattern of pancreas-specific gene expression in the hESC-derived ILCs showed considerable similarity to in vivo pancreas development, and the final population contained representatives of the ductal, exocrine, and endocrine pancreas. The hESC-derived ILCs contained 2%-8% human C-peptide-positive cells, as well as glucagon- and
somatostatin
-positive cells. Insulin content as high as 70 ng of insulin/mug of DNA was measured in the ILCs, representing levels higher than that of human fetal islets. In addition, the hESC-derived ILCs contained numerous secretory granules, as determined by electron microscopy, and secreted human C-peptide in a glucose-dependent manner. Disclosure of potential conflicts of interest is found at the end of this article.
...
PMID:Generation of insulin-producing islet-like clusters from human embryonic stem cells. 1751 Feb 17
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