The embryonic pancreas is thought to develop from pluripotent endodermal cells that give rise to endocrine and exocrine cells. A key guidance mechanism for pancreatic development has previously been found to be epithelial-mesenchymal interaction. Interactions within the epithelium, however, have not been well studied. Glucagon is the earliest peptide hormone present at appreciable levels in the developing pancreatic epithelium (embryonic day [E]-9.5 in mouse). Insulin accumulation begins slightly later (E11 in mouse), followed by a rapid accumulation during the "second wave" of insulin differentiation ( approximately E15). Here we found that blocking early expression and function of glucagon, but not GLP-1, an alternate gene product of preproglucagon mRNA, prevented insulin-positive differentiation in early embryonic (E11) pancreas. These results suggest a novel concept and a key role for glucagon in the paracrine induction of differentiation of other pancreatic components in the early embryonic pancreas.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2337/diabetes.51.11.3229 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Investigating the pathogenicity of the recessive p.A251T variant in monogenic diabetes using iPSC-derived beta-like cells.
medRxiv
December 2024
Centre de Recherche du CHUM, and Faculty of Medicine, University of Montreal, QC, Canada.
Monogenic diabetes, formerly called Maturity-Onset Diabetes of the Young (MODY), involves single-gene mutations, typically with dominant inheritance, and has been associated with variants in 14 genes. Among these, mutations are the most common, and their diagnosis allows the use of alternative therapies, including sulfonylureas. In an earlier study, we described a variant displaying recessive transmission, p.
View Article and Find Full Text PDFA small molecule K-3 promotes PDX1 expression and potentiates the differentiation of pluripotent stem cells into insulin-producing pancreatic β cells.
Stem Cells
November 2024
School of Life Science and Technology, Institute of Science Tokyo, 4259-B-25 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan.
Insulin-producing pancreatic β-like cells derived from human pluripotent stem cells (PSCs) are anticipated as a novel cell source for cell replacement therapy for diabetes patients. Here, we describe the identification of small molecule compounds that promote the differentiation of the PSCs into insulin-producing cells by high throughput screening with a chemical library composed of 55,000 compounds. The initial hit compound K-1 and one derivative K-3 increased the proportion of PSC-derived insulin-positive endocrine cells and their glucose-stimulated insulin secretory (GSIS) functions.
View Article and Find Full Text PDFInhibition of proteasome activity facilitates definitive endodermal specification of pluripotent stem cells by influencing YAP signalling.
Life Sci
December 2024
Manipal Institute of Regenerative Medicine, Bangalore, Manipal Academy of Higher Education, Manipal, India. Electronic address:
Aims: The knowledge of the molecular players that regulate the generation of endoderm cells is imperative to obtain homogenous population of pancreatic β-cells from stem cells. The Ubiquitin proteasome system (UPS) has been envisaged as a crucial intracellular protein degradation system, but its role in the generation of β-cells remains elusive. Hence, it would be appropriate to unravel the potential role of UPS in endoderm specification and utilize the understanding to generate β-cells from pluripotent stem cells.
View Article and Find Full Text PDFXenogenic Engraftment of Human-Induced Pluripotent Stem Cell-Derived Pancreatic Islet Cells in an Immunosuppressive Diabetic Göttingen Mini-Pig Model.
Cell Transplant
October 2024
Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA), Fujisawa, Japan.
In the development of cell therapy products, immunocompromised animal models closer in size to humans are valuable for enhancing the translatability of findings to clinical trials. In the present study, we generated immunocompromised type 1 diabetic Göttingen mini-pig models and demonstrated the engraftment of human-induced pluripotent stem cell-derived pancreatic islet cells (iPICs). We induced hyperglycemia with a concomitant reduction in endogenous C-peptide levels in pigs that underwent thymectomy and splenectomy.
View Article and Find Full Text PDFDifferential lipid signaling from CD4 and CD8 T cells contributes to type 1 diabetes development.
Front Immunol
October 2024
Department of Cell, Developmental, and Integrative Biology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.
Introduction: We reported that Ca-independent phospholipase Aβ (iPLAβ)-derived lipids (iDLs) contribute to type 1 diabetes (T1D) onset. As CD4 and CD8 T cells are critical in promoting β-cell death, we tested the hypothesis that iDL signaling from these cells participates in T1D development.
Methods: CD4 and CD8 T cells from wild-type non-obese diabetic () and .
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!