Article
Islet architecture: A comparative study.
Department of Medicine, The University of Chicago, Chicago, IL, USA.
Islets
1(2):129-36.
DOI:10.4161/isl.1.2.9480
Source: PubMed
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Citations (0)
- Cited In (4)
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Article: Functional connectivity in islets of langerhans from mouse pancreas tissue slices.
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ABSTRACT: We propose a network representation of electrically coupled beta cells in islets of Langerhans. Beta cells are functionally connected on the basis of correlations between calcium dynamics of individual cells, obtained by means of confocal laser-scanning calcium imaging in islets from acute mouse pancreas tissue slices. Obtained functional networks are analyzed in the light of known structural and physiological properties of islets. Focusing on the temporal evolution of the network under stimulation with glucose, we show that the dynamics are more correlated under stimulation than under non-stimulated conditions and that the highest overall correlation, largely independent of Euclidean distances between cells, is observed in the activation and deactivation phases when cells are driven by the external stimulus. Moreover, we find that the range of interactions in networks during activity shows a clear dependence on the Euclidean distance, lending support to previous observations that beta cells are synchronized via calcium waves spreading throughout islets. Most interestingly, the functional connectivity patterns between beta cells exhibit small-world properties, suggesting that beta cells do not form a homogeneous geometric network but are connected in a functionally more efficient way. Presented results provide support for the existing knowledge of beta cell physiology from a network perspective and shed important new light on the functional organization of beta cell syncitia whose structural topology is probably not as trivial as believed so far.PLoS Computational Biology 02/2013; 9(2):e1002923. · 5.22 Impact Factor -
Article: Pancreatic beta-cell failure in obese mice with human-like CMP-Neu5Ac hydroxylase deficiency.
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ABSTRACT: Type 2 diabetes is highly prevalent in human populations, particularly in obese individuals, and is characterized by progressive pancreatic β-cell dysfunction and insulin resistance. Most mammals, including Old World primates, express two major kinds of sialic acids, N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), typically found at the distal ends of glycoconjugate chains at the cell surface. Humans are uniquely unable to produce endogenous Neu5Gc due to an inactivating mutation in the CMP-Neu5Ac hydroxylase (CMAH) gene. The CMAH enzyme catalyzes the generation of CMP-Neu5Gc by the transfer of a single oxygen atom to the acyl group of CMP-Neu5Ac. Here, we show that mice bearing a human-like deletion of the Cmah gene exhibit fasting hyperglycemia and glucose intolerance following a high-fat diet. This phenotype is caused not by worsened insulin resistance but by compromised pancreatic β-cell function associated with a 65% decrease in islet size and area and 50% decrease in islet number. Obese Cmah-null mice also show an ∼40% reduction in response to insulin secretagogues in vivo. These findings show that human evolution-like changes in sialic acid composition impair pancreatic β-cell function and exacerbate glucose intolerance in mice. This may lend insight into the pathogenesis of type 2 diabetes in obese humans.The FASEB Journal 02/2011; 25(6):1887-93. · 5.71 Impact Factor -
Article: Altered islet composition and disproportionate loss of large islets in patients with type 2 diabetes.
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ABSTRACT: Human islets exhibit distinct islet architecture with intermingled alpha- and beta-cells particularly in large islets. In this study, we quantitatively examined pathological changes of the pancreas in patients with type 2 diabetes (T2D). Specifically, we tested a hypothesis that changes in endocrine cell mass and composition are islet-size dependent. A large-scale analysis of cadaveric pancreatic sections from T2D patients (n = 12) and non-diabetic subjects (n = 14) was carried out combined with semi-automated analysis to quantify changes in islet architecture. The method provided the representative islet distribution in the whole pancreas section that allowed us to examine details of endocrine cell composition in individual islets. We observed a preferential loss of large islets (>60 µm in diameter) in T2D patients compared to non-diabetic subjects. Analysis of islet cell composition revealed that the beta-cell fraction in large islets was decreased in T2D patients. This change was accompanied by a reciprocal increase in alpha-cell fraction, however total alpha-cell area was decreased along with beta-cells in T2D. Delta-cell fraction and area remained unchanged. The computer-assisted quantification of morphological changes in islet structure minimizes sampling bias. Significant beta-cell loss was observed in large islets in T2D, in which alpha-cell ratio reciprocally increased. However, there was no alpha-cell expansion and the total alpha-cell area was also decreased. Changes in islet architecture were marked in large islets. Our method is widely applicable to various specimens using standard immunohistochemical analysis that may be particularly useful to study large animals including humans where large organ size precludes manual quantitation of organ morphology.PLoS ONE 01/2011; 6(11):e27445. · 4.09 Impact Factor
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Keywords
alpha-
bird pancreas
delta-cell population predominates
delta-cells
different hormone-secreting cell types
distinct differences
Emerging reports
human islet physiology
human islets
islet architecture
islet sizes
islets
Markedly large islets
monkey islets
mouse islets
mouse islets share common architectural features
pancreas size
pregnant mice
total beta-cell mass
various mouse models