scholarly journals Increased NKX6.1 expression and decreased ARX expression in alpha cells accompany reduced beta-cell volume in human subjects

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yukari Fujita ◽  
Junji Kozawa ◽  
Kenji Fukui ◽  
Hiromi Iwahashi ◽  
Hidetoshi Eguchi ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Beta Cell ◽  
Cell Volume ◽  
Islet Cells ◽  
Human Subjects ◽  
Expression Patterns ◽  
Human Pancreas ◽  
Cell Area ◽  
Beta Cell Volume ◽  
Cell Conversion

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.

Gluten-free diet increases beta-cell volume and improves glucose tolerance in an animal model of type 2 diabetes

2016 ◽  
Vol 32 (7) ◽  
pp. 675-684 ◽  
Author(s):  
Martin Haupt-Jorgensen ◽  
Karsten Buschard ◽  
Axel K. Hansen ◽  
Knud Josefsen ◽  
Julie Christine Antvorskov
Keyword(s):  
Type 2 Diabetes ◽  
Animal Model ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Cell Volume ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Beta Cell Volume

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

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.

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 ◽  
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

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 ◽  
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

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

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

scholarly journals Autoantigen Treatment in Type 1 Diabetes: Unsolved Questions on How to Select Autoantigen and Administration Route

2020 ◽  
Vol 21 (5) ◽  
pp. 1598 ◽  
Author(s):  
Johnny Ludvigsson
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Human Subjects ◽  
Subcutaneous Administration ◽  
Acid Decarboxylase ◽  
Recent Onset ◽  
Prevention Trials

Autoantigen treatment has been tried for the prevention of type 1 diabetes (T1D) and to preserve residual beta-cell function in patients with a recent onset of the disease. In experimental animal models, efficacy was good, but was insufficient in human subjects. Besides the possible minor efficacy of peroral insulin in high-risk individuals to prevent T1D, autoantigen prevention trials have failed. Other studies on autoantigen prevention and intervention at diagnosis are ongoing. One problem is to select autoantigen/s; others are dose and route. Oral administration may be improved by using different vehicles. Proinsulin peptide therapy in patients with T1D has shown possible minor efficacy. In patients with newly diagnosed T1D, subcutaneous injection of glutamic acid decarboxylase (GAD) bound to alum hydroxide (GAD-alum) can likely preserve beta-cell function, but the therapeutic effect needs to be improved. Intra-lymphatic administration may be a better alternative than subcutaneous administration, and combination therapy might improve efficacy. This review elucidates some actual problems of autoantigen therapy in the prevention and/or early intervention of type 1 diabetes.

scholarly journals Expression patterns of signalling molecules and transcription factors in the early rabbit embryo and their significance for modelling amniote axis formation

2021 ◽  
Author(s):  
Ruben Plöger ◽  
Christoph Viebahn
Keyword(s):  
Transcription Factors ◽  
Expression Patterns ◽  
In Situ Hybridisation ◽  
Body Plan ◽  
The Body ◽  
Anchor Point ◽  
Axis Formation ◽  
Point Model ◽  
Signalling Molecules ◽  
Rabbit Embryo

AbstractThe anterior-posterior axis is a central element of the body plan and, during amniote gastrulation, forms through several transient domains with specific morphogenetic activities. In the chick, experimentally proven activity of signalling molecules and transcription factors lead to the concept of a ‘global positioning system’ for initial axis formation whereas in the (mammotypical) rabbit embryo, a series of morphological or molecular domains are part of a putative ‘three-anchor-point model’. Because circular expression patterns of genes involved in axis formation exist in both amniote groups prior to, and during, gastrulation and may thus be suited to reconcile these models, the expression patterns of selected genes known in the chick, namely the ones coding for the transcription factors eomes and tbx6, the signalling molecule wnt3 and the wnt inhibitor pkdcc, were analysed in the rabbit embryonic disc using in situ hybridisation and placing emphasis on their germ layer location. Peripheral wnt3 and eomes expression in all layers is found initially to be complementary to central pkdcc expression in the hypoblast during early axis formation. Pkdcc then appears — together with a posterior-anterior gradient in wnt3 and eomes domains — in the epiblast posteriorly before the emerging primitive streak is marked by pkdcc and tbx6 at its anterior and posterior extremities, respectively. Conserved circular expression patterns deduced from some of this data may point to shared mechanisms in amniote axis formation while the reshaping of localised gene expression patterns is discussed as part of the ‘three-anchor-point model’ for establishing the mammalian body plan.

Expression and distribution of the Na+- HCO 3 − cotransporter in human pancreas

1999 ◽  
Vol 277 (2) ◽  
pp. G487-G494 ◽  
Author(s):  
Christopher R. Marino ◽  
Virginia Jeanes ◽  
Walter F. Boron ◽  
Bernhard M. Schmitt
Keyword(s):  
Northern Blot ◽  
Islet Cells ◽  
Rat Kidney ◽  
Physiological Role ◽  
Human Pancreas ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cellular Mechanisms ◽  
Double Labeling ◽  
Normal Human

The cellular mechanisms of [Formula: see text] secretion in the human pancreas are unclear. Expression of a Na+-[Formula: see text]cotransporter (NBC) mRNA has been observed recently, but the distribution and physiological role of the NBC protein are not known. Here we examined the expression and localization of NBC in human pancreas by Northern blot, immunoblot, and immunofluorescence microscopy. Rat kidney NBC probes detected a single 9.5-kb band by Northern blot. On immunoblots, two polyclonal antisera directed against different epitopes of rat kidney NBC identified a single ∼130-kDa protein. In cryosections of normal human pancreas, both antisera labeled basolateral membranes of large, morphologically identifiable ducts and produced a distinct labeling pattern in the remainder of the parenchyma. In double-labeling experiments, NBC immunoreactivity in the parenchyma colocalized with the Na+-K+pump, a basolateral marker. In contrast, NBC and cystic fibrosis transmembrane conductance regulator, an apical membrane marker, were detected within the same histological structures but at different subcellular localizations. The NBC antisera did not label acinar or islet cells. Our observations suggest that secretion of[Formula: see text] by human pancreatic duct cells involves the basolateral uptake of Na+and[Formula: see text] via NBC, an electrogenic Na+-[Formula: see text]cotransporter.

Sign in / Sign up

Export Citation Format

Share Document