Morphometric Study of the beta-cell Volume of the Canine Pancreas with Consideration of the Axis of Tissue Transection

AbstractPancreatic islet cells have plasticity, such as the abilities to dedifferentiate and transdifferentiate. Islet cell conversion to other characteristic cell is largely determined by transcription factors, but significance of expression patterns of these transcription factors in human islet cells remained unclear. Here, we present the NKX6.1-positive ratio of glucagon-positive cells (NKX6.1+/GCG+ ratio) and the ARX-negative ratio of glucagon-positive cells (ARX−/GCG+ ratio) in 34 patients who were not administered antidiabetic agents. Both of NKX6.1+/GCG+ ratio and ARX−/GCG+ ratio negatively associated with relative beta cell area. And these ratios did not have significant correlation with other parameters including age, body mass index, hemoglobin A1c, fasting plasma glucose level or relative alpha-cell area. Our data demonstrate that these expression ratios of transcription factors in glucagon-positive cells closely correlate with the reduction of beta-cell volume in human pancreas.

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3D quantification of changes in pancreatic islets in mouse models of diabetes type I and II

Disease Models & Mechanisms ◽

10.1242/dmm.045351 ◽

2020 ◽

Vol 13 (12) ◽

pp. dmm045351

Author(s):

Urmas Roostalu ◽

Jacob Lercke Skytte ◽

Casper Gravesen Salinas ◽

Thomas Klein ◽

Niels Vrang ◽

...

Keyword(s):

Blood Glucose ◽

Beta Cell ◽

Cell Volume ◽

Beta Cells ◽

Mouse Models ◽

Cell Mass ◽

Beta Cell Mass ◽

Light Sheet ◽

Type I ◽

Beta Cell Volume

ABSTRACTDiabetes is characterized by rising levels of blood glucose and is often associated with a progressive loss of insulin-producing beta cells. Recent studies have demonstrated that it is possible to regenerate new beta cells through proliferation of existing beta cells or trans-differentiation of other cell types into beta cells, raising hope that diabetes can be cured through restoration of functional beta cell mass. Efficient quantification of beta cell mass and islet characteristics is needed to enhance drug discovery for diabetes. Here, we report a 3D quantitative imaging platform for unbiased evaluation of changes in islets in mouse models of type I and II diabetes. To determine whether the method can detect pharmacologically induced changes in beta cell volume, mice were treated for 14 days with either vehicle or the insulin receptor antagonist S961 (2.4 nmol/day) using osmotic minipumps. Mice treated with S961 displayed increased blood glucose and insulin levels. Light-sheet imaging of insulin and Ki67 (also known as Mki67)-immunostained pancreata revealed a 43% increase in beta cell volume and 21% increase in islet number. S961 treatment resulted in an increase in islets positive for the cell proliferation marker Ki67, suggesting that proliferation of existing beta cells underlies the expansion of total beta cell volume. Using light-sheet imaging of a non-obese diabetic mouse model of type I diabetes, we also characterized the infiltration of CD45 (also known as PTPRC)-labeled leukocytes in islets. At 14 weeks, 40% of the small islets, but more than 80% of large islets, showed leukocyte infiltration. These results demonstrate how quantitative light-sheet imaging can capture changes in individual islets to help pharmacological research in diabetes.

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Synergistic Effects of Long-Term Combination Therapy of DPP-4 Inhibitor and SGLT2 Inhibitor on the Preservation of Beta-Cell Volume in Rats with Type 2 Diabetes

Diabetes ◽

10.2337/db18-2132-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 2132-P

Author(s):

HIROKI MIZUKAMI ◽

DANYANG GUO ◽

KAZUHISA TAKAHASHI ◽

SHO OSONOI ◽

SAORI OGASAWARA ◽

...

Keyword(s):

Type 2 Diabetes ◽

Combination Therapy ◽

Beta Cell ◽

Cell Volume ◽

Synergistic Effects ◽

Sglt2 Inhibitor ◽

Beta Cell Volume

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2127-P: Reduced Islet Parasympathetic Nerve Density Correlates with Decrease in Beta-Cell Volume of Islet in Lean Type 2 Diabetic Goto-Kakizaki Rat

Diabetes ◽

10.2337/db19-2127-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 2127-P

Author(s):

HIROKI MIZUKAMI ◽

DANYANG GUO ◽

KAZUHISA TAKAHASHI ◽

SHO OSONOI ◽

KAZUHIRO KUDO ◽

...

Keyword(s):

Beta Cell ◽

Cell Volume ◽

Parasympathetic Nerve ◽

Beta Cell Volume ◽

Type 2 Diabetic

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PS2 - 8. Correlation of beta cell volume and SPECT signal in transplanted islets, using In-111 labeled exendin-3

Nederlands Tijdschrift voor Diabetologie ◽

10.1007/s12467-013-0141-4 ◽

2013 ◽

Vol 11 (4) ◽

pp. 186-187

Author(s):

Inge van der Kroon ◽

Cathelijne Frielink ◽

Lieke Joosten ◽

Desiree Bos ◽

Maarten Brom ◽

...

Keyword(s):

Beta Cell ◽

Cell Volume ◽

Beta Cell Volume

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Determination of secretory granule maturation times in pancreatic islet beta-cells by serial block face scanning electron microscopy

10.1101/865683 ◽

2019 ◽

Author(s):

A. Rao ◽

E.L. McBride ◽

G. Zhang ◽

H. Xu ◽

T. Cai ◽

...

Keyword(s):

Electron Microscopy ◽

Beta Cell ◽

Pancreatic Islets ◽

Beta Cells ◽

Secretory Granule ◽

Secretory Granules ◽

Pancreatic Islets Of Langerhans ◽

Beta Cell Volume ◽

Block Face ◽

Electron Lucent

AbstractIt is shown how serial block-face electron microscopy (SBEM) of insulin-secreting beta cells in wild-type mouse pancreatic islets of Langerhans can be used to determine maturation times of secretory granules. Although SBEM captures the beta cell structure at a snapshot in time, the observed ultrastructure can be considered representative of a dynamic equilibrium state of the cells since the pancreatic islets are maintained in culture in approximate homeostasis. It is found that 7.2±1.2% (±st. dev.) of the beta cell volume is composed of secretory granule dense-cores exhibiting angular shapes surrounded by wide (typically ≳100 nm) electron-lucent halos. These organelles are identified as mature granules that store insulin for regulated release through the plasma membrane, with a release time of 96±12 hours, as previously obtained from pulsed 35S-radiolabeling of cysteine and methionine. Analysis of beta cell 3D volumes reveals a subpopulation of secretory organelles without electron-lucent halos, identified as immature secretory granules. Another subpopulation of secretory granules is found with thin (typically ≲30 nm) electron-lucent halos, which are attributed to immature granules that are transforming from proinsulin to insulin by action of prohormone convertases. From the volume ratio of proinsulin in the immature granules to insulin in the mature granules, we estimate that the newly formed immature granules remain in morphologically-defined immature states for an average time of 135±14 minutes, and the immature transforming granules for an average time of 130±17 minutes.

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Possible Prevention of Diabetes with a Gluten-Free Diet

Nutrients ◽

10.3390/nu10111746 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1746 ◽

Cited By ~ 5

Author(s):

Martin Haupt-Jorgensen ◽

Laurits Holm ◽

Knud Josefsen ◽

Karsten Buschard

Keyword(s):

Beta Cell ◽

Animal Studies ◽

Current Knowledge ◽

Human Study ◽

Intestinal Barrier ◽

Gluten Free ◽

Gluten Peptides ◽

Beta Cell Volume ◽

Intervention Trials ◽

Inflammatory Milieu

Gluten seems a potentially important determinant in type 1 diabetes (T1D) and type 2 diabetes (T2D). Intake of gluten, a major component of wheat, rye, and barley, affects the microbiota and increases the intestinal permeability. Moreover, studies have demonstrated that gluten peptides, after crossing the intestinal barrier, lead to a more inflammatory milieu. Gluten peptides enter the pancreas where they affect the morphology and might induce beta-cell stress by enhancing glucose- and palmitate-stimulated insulin secretion. Interestingly, animal studies and a human study have demonstrated that a gluten-free (GF) diet during pregnancy reduces the risk of T1D. Evidence regarding the role of a GF diet in T2D is less clear. Some studies have linked intake of a GF diet to reduced obesity and T2D and suggested a role in reducing leptin- and insulin-resistance and increasing beta-cell volume. The current knowledge indicates that gluten, among many environmental factors, may be an aetiopathogenic factors for development of T1D and T2D. However, human intervention trials are needed to confirm this and the proposed mechanisms.

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