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Islet formation during the neonatal development in mice.

Miller K, Kim A, Kilimnik G, Jo J, Moka U, Periwal V, Hara M - PLoS ONE (2009)

Bottom Line: Our study has revealed long stretches of interconnected islets located along large blood vessels in the neonatal pancreas.Alpha-cells span the elongated islet-like structures, which we hypothesize represent sites of fission and facilitate the eventual formation of discrete islets.Mathematical modeling of the fission process in the neonatal islet formation is also presented.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, The University of Chicago, Chicago, IL, USA.

ABSTRACT
The islet of Langerhans is a unique micro-organ within the exocrine pancreas, which is composed of insulin-secreting beta-cells, glucagon-secreting alpha-cells, somatostatin-secreting delta-cells, pancreatic polypeptide-secreting PP cells and ghrelin-secreting epsilon-cells. Islets also contain non-endocrine cell types such as endothelial cells. However, the mechanism(s) of islet formation is poorly understood due to technical difficulties in capturing this dynamic event in situ. We have developed a method to monitor beta-cell proliferation and islet formation in the intact pancreas using transgenic mice in which the beta-cells are specifically tagged with a fluorescent protein. Endocrine cells proliferate contiguously, forming branched cord-like structures in both embryos and neonates. Our study has revealed long stretches of interconnected islets located along large blood vessels in the neonatal pancreas. Alpha-cells span the elongated islet-like structures, which we hypothesize represent sites of fission and facilitate the eventual formation of discrete islets. We propose that islet formation occurs by a process of fission following contiguous endocrine cell proliferation, rather than by local aggregation or fusion of isolated beta-cells and islets. Mathematical modeling of the fission process in the neonatal islet formation is also presented.

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Related in: MedlinePlus

Quantification of beta-cell proliferation and islet development.A: A histogram showing the distribution of islets (including small clusters of beta-cells) in the neonatal pancreas (P1-P21). a. The distribution of total beta-cell mass is shown in the increments of 1×103 µm2. Note that beta-cell mass larger than 10×103 µm2 is compiled in the last column. b. Beta-cell mass larger than 10×103 µm2 shown in A.a is partitioned in the increments of 10×103 µm2. Note the difference in frequency (Y-axis) from the histogram shown in A.a. B: 3D scatter plot. Each dot represents a single islet/cluster with reference to size (area) and shape (circularity and Feret's diameter). Note that all plots are in the same scale.
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pone-0007739-g002: Quantification of beta-cell proliferation and islet development.A: A histogram showing the distribution of islets (including small clusters of beta-cells) in the neonatal pancreas (P1-P21). a. The distribution of total beta-cell mass is shown in the increments of 1×103 µm2. Note that beta-cell mass larger than 10×103 µm2 is compiled in the last column. b. Beta-cell mass larger than 10×103 µm2 shown in A.a is partitioned in the increments of 10×103 µm2. Note the difference in frequency (Y-axis) from the histogram shown in A.a. B: 3D scatter plot. Each dot represents a single islet/cluster with reference to size (area) and shape (circularity and Feret's diameter). Note that all plots are in the same scale.

Mentions: A macro was written for ImageJ to automate the measurement of beta-cell mass, islet number, and size distribution from fluorescent images (Data S1 and Movie S2 online). The overall distribution of islets (including small clusters of beta-cells) in the neonatal pancreas (P1-P21) is shown in a histogram (Fig. 2A.a). Beta-cell mass larger than 10×103 µm2 is further partitioned in increments of 10×103 µm2 (Fig. 2A.b). Note that a similar size distribution is observed throughout neonatal development with increasing frequency in each bin as the animals age. Interestingly, there is a constant increase in the number of small clusters as well. Histograms with SEM and information on body and pancreas weight, total number of islets, and beta-cell mass normalized to pancreas weight at each time point are provided in Figure S1 online.


Islet formation during the neonatal development in mice.

Miller K, Kim A, Kilimnik G, Jo J, Moka U, Periwal V, Hara M - PLoS ONE (2009)

Quantification of beta-cell proliferation and islet development.A: A histogram showing the distribution of islets (including small clusters of beta-cells) in the neonatal pancreas (P1-P21). a. The distribution of total beta-cell mass is shown in the increments of 1×103 µm2. Note that beta-cell mass larger than 10×103 µm2 is compiled in the last column. b. Beta-cell mass larger than 10×103 µm2 shown in A.a is partitioned in the increments of 10×103 µm2. Note the difference in frequency (Y-axis) from the histogram shown in A.a. B: 3D scatter plot. Each dot represents a single islet/cluster with reference to size (area) and shape (circularity and Feret's diameter). Note that all plots are in the same scale.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2770846&req=5

pone-0007739-g002: Quantification of beta-cell proliferation and islet development.A: A histogram showing the distribution of islets (including small clusters of beta-cells) in the neonatal pancreas (P1-P21). a. The distribution of total beta-cell mass is shown in the increments of 1×103 µm2. Note that beta-cell mass larger than 10×103 µm2 is compiled in the last column. b. Beta-cell mass larger than 10×103 µm2 shown in A.a is partitioned in the increments of 10×103 µm2. Note the difference in frequency (Y-axis) from the histogram shown in A.a. B: 3D scatter plot. Each dot represents a single islet/cluster with reference to size (area) and shape (circularity and Feret's diameter). Note that all plots are in the same scale.
Mentions: A macro was written for ImageJ to automate the measurement of beta-cell mass, islet number, and size distribution from fluorescent images (Data S1 and Movie S2 online). The overall distribution of islets (including small clusters of beta-cells) in the neonatal pancreas (P1-P21) is shown in a histogram (Fig. 2A.a). Beta-cell mass larger than 10×103 µm2 is further partitioned in increments of 10×103 µm2 (Fig. 2A.b). Note that a similar size distribution is observed throughout neonatal development with increasing frequency in each bin as the animals age. Interestingly, there is a constant increase in the number of small clusters as well. Histograms with SEM and information on body and pancreas weight, total number of islets, and beta-cell mass normalized to pancreas weight at each time point are provided in Figure S1 online.

Bottom Line: Our study has revealed long stretches of interconnected islets located along large blood vessels in the neonatal pancreas.Alpha-cells span the elongated islet-like structures, which we hypothesize represent sites of fission and facilitate the eventual formation of discrete islets.Mathematical modeling of the fission process in the neonatal islet formation is also presented.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, The University of Chicago, Chicago, IL, USA.

ABSTRACT
The islet of Langerhans is a unique micro-organ within the exocrine pancreas, which is composed of insulin-secreting beta-cells, glucagon-secreting alpha-cells, somatostatin-secreting delta-cells, pancreatic polypeptide-secreting PP cells and ghrelin-secreting epsilon-cells. Islets also contain non-endocrine cell types such as endothelial cells. However, the mechanism(s) of islet formation is poorly understood due to technical difficulties in capturing this dynamic event in situ. We have developed a method to monitor beta-cell proliferation and islet formation in the intact pancreas using transgenic mice in which the beta-cells are specifically tagged with a fluorescent protein. Endocrine cells proliferate contiguously, forming branched cord-like structures in both embryos and neonates. Our study has revealed long stretches of interconnected islets located along large blood vessels in the neonatal pancreas. Alpha-cells span the elongated islet-like structures, which we hypothesize represent sites of fission and facilitate the eventual formation of discrete islets. We propose that islet formation occurs by a process of fission following contiguous endocrine cell proliferation, rather than by local aggregation or fusion of isolated beta-cells and islets. Mathematical modeling of the fission process in the neonatal islet formation is also presented.

Show MeSH
Related in: MedlinePlus