scholarly journals Diabetes-Resistant NOR Mice Are More Severely Affected by Streptozotocin Compared to the Diabetes-Prone NOD Mice: Correlations with Liver and Kidney GLUT2 Expressions

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
S. Kahraman ◽  
C. Aydin ◽  
G. O. Elpek ◽  
E. Dirice ◽  
A. D. Sanlioglu
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Glucose Transporter ◽  
Expression Profiles ◽  
Nod Mice ◽  
Underlying Mechanism ◽  
Expression Levels ◽  
Similar Dose ◽  
Liver And Kidney ◽  
Immunohistochemical Studies

Nonobese Diabetic (NOD) mice are susceptible strains for Type 1 diabetes development, and Nonobese Diabetes-Resistant (NOR) mice are defined as suitable controls for NOD mice in non-MHC-related research. Diabetes is often accelerated in NOD mice via Streptozotocin (STZ). STZ is taken inside cells via GLUT2 transmembrane carrier proteins, the major glucose transporter isoforms in pancreatic beta cells, liver, kidneys, and the small intestine. We observed severe adverse effects in NOR mice treated with STZ compared to NOD mice that were made diabetic with a similar dose. We suggested that the underlying mechanism could be differential GLUT2 expressions in pancreatic beta cells, yet immunofluorescent and immunohistochemical studies revealed similar GLUT2 expression levels. We also detected GLUT2 expression profiles in NOD and NOR hepatic and renal tissues by western blot analysis and observed considerably higher GLUT2 expression levels in liver and kidney tissues of NOR mice. Although beta cell GLUT2 expression levels are frequently evaluated as a marker predicting STZ sensitivity in animal models, we report here very different diabetic responses to STZ in two different animal strains, in spite of similar initial GLUT2 expressions in beta cells. Furthermore, use of NOR mice in STZ-mediated experimental diabetes settings should be considered accordingly.

Morphological analysis of selective destruction of pancreatic beta-cells by cytotoxic T lymphocytes in NOD mice

Diabetes ◽  
1991 ◽  
Vol 40 (9) ◽  
pp. 1210-1217 ◽  
Author(s):  
M. Hayakawa ◽  
K. Yokono ◽  
M. Nagata ◽  
N. Hatamori ◽  
W. Ogawa ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Beta Cells ◽  
Cytotoxic T Lymphocytes ◽  
Pancreatic Beta Cells ◽  
Morphological Analysis ◽  
Nod Mice ◽  
Selective Destruction

Glucose modulates glucose transporter affinity, glucokinase activity, and secretory response in rat pancreatic beta-cells

Diabetes ◽  
1993 ◽  
Vol 42 (1) ◽  
pp. 199-205 ◽  
Author(s):  
F. Purrello ◽  
M. Buscema ◽  
A. M. Rabuazzo ◽  
V. Caltabiano ◽  
F. Forte ◽  
...  
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Glucose Transporter ◽  
Secretory Response

scholarly journals Replacing murine insulin 1 with human insulin protects NOD mice from diabetes

2019 ◽  
Author(s):  
Colleen M. Elso ◽  
Nicholas A. Scott ◽  
Lina Mariana ◽  
Emma I. Masterman ◽  
Andrew P.R. Sutherland ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cells ◽  
Mouse Models ◽  
Human Insulin ◽  
Murine Model ◽  
Pancreatic Beta Cells ◽  
Autoimmune Diabetes ◽  
Nod Mice ◽  
Human Type 1 Diabetes

AbstractType 1, or autoimmune, diabetes is caused by the T-cell mediated destruction of the insulin-producing pancreatic beta cells. Non-obese diabetic (NOD) mice spontaneously develop autoimmune diabetes akin to human type 1 diabetes. For this reason, the NOD mouse has been the preeminent murine model for human type 1 diabetes research for several decades. However, humanized mouse models are highly sought after because they offer both the experimental tractability of a mouse model and the clinical relevance of human-based research. Autoimmune T-cell responses against insulin, and its precursor proinsulin, play central roles in the autoimmune responses against pancreatic beta cells in both humans and NOD mice. As a first step towards developing a murine model of the human autoimmune response against pancreatic beta cells we set out to replace the murine insulin 1 gene (Ins1) with the human insulin gene (INS) using CRISPR/Cas9. Here we describe a NOD mouse strain that expresses human insulin in place of murine insulin 1, referred to as HuPI. HuPI mice express human insulin, and C-peptide, in their serum and pancreata and have normal glucose tolerance. Compared with wild type NOD mice, the incidence of diabetes is much lower in HuPI mice. Only 15-20% of HuPI mice developed diabetes after 300 days, compared to more than 60% of unmodified NOD mice. Immune-cell infiltration into the pancreatic islets of HuPI mice was not detectable at 100 days but was clearly evident by 300 days. This work highlights the feasibility of using CRISPR/Cas9 to create mouse models of human diseases that express proteins pivotal to the human disease. Furthermore, it reveals that even subtle changes in proinsulin protect NOD mice from diabetes.

scholarly journals Porcine colonoids and enteroids keep the memory of their origin during regeneration.

2021 ◽  
Author(s):  
Alicia M. Barnett ◽  
Jane A. Mullaney ◽  
Charlotte Hendriks ◽  
Lisa Le Borgne ◽  
Warren C. McNabb ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glucose Transporter ◽  
Expression Profiles ◽  
Cell Types ◽  
Specific Cell ◽  
Stem Cell Markers ◽  
Culture Methods ◽  
Glucose Transporter 1 ◽  
Expression Levels

The development of alternative in vitro culture methods has increased in the last decade as three-dimensional organoids of various tissues, including those of the small and large intestines. Due to their multicellular composition, organoids offer advantages over traditionally used immortalized or primary cell lines. However, organoids must be accurate models of their tissues of origin. This study compared gene expression profiles with respect to markers of specific cell-types (stem-cells, enterocytes, goblet and enteroendocrine cells) and barrier maturation (tight junctions) of colonoid and enteroid cultures with their tissues of origin, and colonoids with enteroids. Colonoids derived from three healthy pigs formed multi-lobed structures with a monolayer of cells similar to the crypt structures in colonic tissue. Colonoid and enteroid gene expression signatures were more similar to those found for the tissues of their origin than to each other. However, relative to their derived tissues, organoids had increased gene expression levels of stem-cell markers Sox9 and Lgr5 encoding Sex determining region Y-box 9 and leucine-rich repeat-containing G-protein coupled rector 5, respectively. In contrast, expression levels of Occl and Zo1 encoding occludin and zonula occludens 1 respectively, were decreased. Expression levels of the cell lineage markers Atoh1, Cga and Muc2 encoding atonal homolog 1, chromogranin A and mucin 2 respectively, were decreased in colonoids, while Sglt1 and Apn encoding sodium-glucose transporter 1 and aminopeptidase A respectively, were decreased in enteroids. These results indicate colonoid and enteroid cultures were predominantly comprised of undifferentiated cell-types with decreased barrier maturation relative to their tissues of origin.

scholarly journals Characterisation of Ppy-lineage cells clarifies the functional heterogeneity of pancreatic beta cells in mice

Diabetologia ◽  
2021 ◽  
Author(s):  
Takahiro Fukaishi ◽  
Yuko Nakagawa ◽  
Ayako Fukunaka ◽  
Takashi Sato ◽  
Akemi Hara ◽  
...  
Keyword(s):  
Gene Expression ◽  
Beta Cell ◽  
Single Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Endocrine Cells ◽  
Expression Profiles ◽  
Data Availability ◽  
Valuable Insight ◽  
A Minor

Abstract Aims/hypothesis Pancreatic polypeptide (PP) cells, which secrete PP (encoded by the Ppy gene), are a minor population of pancreatic endocrine cells. Although it has been reported that the loss of beta cell identity might be associated with beta-to-PP cell-fate conversion, at present, little is known regarding the characteristics of Ppy-lineage cells. Methods We used Ppy-Cre driver mice and a PP-specific monoclonal antibody to investigate the association between Ppy-lineage cells and beta cells. The molecular profiles of endocrine cells were investigated by single-cell transcriptome analysis and the glucose responsiveness of beta cells was assessed by Ca2+ imaging. Diabetic conditions were experimentally induced in mice by either streptozotocin or diphtheria toxin. Results Ppy-lineage cells were found to contribute to the four major types of endocrine cells, including beta cells. Ppy-lineage beta cells are a minor subpopulation, accounting for 12–15% of total beta cells, and are mostly (81.2%) localised at the islet periphery. Unbiased single-cell analysis with a Ppy-lineage tracer demonstrated that beta cells are composed of seven clusters, which are categorised into two groups (i.e. Ppy-lineage and non-Ppy-lineage beta cells). These subpopulations of beta cells demonstrated distinct characteristics regarding their functionality and gene expression profiles. Ppy-lineage beta cells had a reduced glucose-stimulated Ca2+ signalling response and were increased in number in experimental diabetes models. Conclusions/interpretation Our results indicate that an unexpected degree of beta cell heterogeneity is defined by Ppy gene activation, providing valuable insight into the homeostatic regulation of pancreatic islets and future therapeutic strategies against diabetes. Data availability The single-cell RNA sequence (scRNA-seq) analysis datasets generated in this study have been deposited in the Gene Expression Omnibus (GEO) under the accession number GSE166164 (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE166164). Graphical abstract

scholarly journals MicroRNAs Regulate the Wnt/Ca2+ Signaling Pathway to Promote the Secretion of Insulin in Pancreatic Nestin-Positive Progenitor Cells

2014 ◽  
Author(s):  
Chunyu Bai ◽  
Xiangchen Li ◽  
Yuhua Gao ◽  
Taofeng Lu ◽  
Kunfu Wang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Progenitor Cells ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Target Genes ◽  
Cell Function ◽  
Expression Profiles ◽  
Control Cell ◽  
Small Noncoding Rnas ◽  
And Function

MicroRNAs (miRNAs) are small noncoding RNAs that bind to the 3?-UTR of mRNAs and function mainly in post-transcriptional regulation. MiRNAs have been implicated to play roles in organ development, including that of the pancreas. Many miRNAs, such as miR-375, miR-124, miR-7, miR-21 and miR-221, have been shown to regulate insulin production as well as insulin secretion. However, it is not known whether miRNAs can regulate insulin secretion via the control of intracellular Ca2+ in pancreatic beta cells. In this research, expression profiles of miRNAs and mRNAs were investigated using RNA-sequencing and microarray analysis in chicken pancreatic nestin-positive progenitor cells and differentiated pancreatic beta cells. A number of miRNAs were up-regulated after differentiation of progenitors into beta cells, which regulate cell signaling pathways to control cell function. miR-223 and miR146a were shown to promote insulin secretion from pancreatic beta cells by regulating the concentration of intracellular Ca2+ via the down-regulation of their target genes.

N-glycosylation modulates the membrane sub-domain distribution and activity of glucose transporter 2 in pancreatic beta cells

2013 ◽  
Vol 434 (2) ◽  
pp. 346-351 ◽  
Author(s):  
Kazuaki Ohtsubo ◽  
Shinji Takamatsu ◽  
Congxiao Gao ◽  
Hiroaki Korekane ◽  
Tsutomu M. Kurosawa ◽  
...  
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Glucose Transporter ◽  
Glucose Transporter 2
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