scholarly journals Alpha to beta cell conversion in the postpartum mouse pancreas involves lgr5 progeny

Diabetes ◽  
2021 ◽  
pp. db201059
Author(s):  
Uylissa A. Rodriguez ◽  
Mairobys Socorro ◽  
Angela Criscimanna ◽  
Christina P. Martins ◽  
Nada Mohamed ◽  
...  
Keyword(s):  
Beta Cell ◽  
Mouse Pancreas ◽  
Cell Conversion

scholarly journals Increased alpha and beta cell mass during mouse pregnancy is not dependent on transdifferentiation

2020 ◽  
pp. 153537022097268
Author(s):  
Sandra K Szlapinski ◽  
Jamie Bennett ◽  
Brenda J Strutt ◽  
David J Hill
Keyword(s):  
Beta Cell ◽  
Fluorescent Protein ◽  
Control Diet ◽  
Yellow Fluorescent Protein ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Alpha Cell ◽  
Β Cell ◽  
Cell Conversion

Maternal pancreatic beta-cell mass (BCM) increases during pregnancy to compensate for relative insulin resistance. If BCM expansion is suboptimal, gestational diabetes mellitus can develop. Alpha-cell mass (ACM) also changes during pregnancy, but there is a lack of information about α-cell plasticity in pregnancy and whether α- to β-cell transdifferentiation can occur. To investigate this, we used a mouse model of gestational glucose intolerance induced by feeding low-protein (LP) diet from conception until weaning and compared pregnant female offspring to control diet-fed animals. Control and LP pancreata were collected for immunohistochemical analysis and serum glucagon levels were measured. In order to lineage trace α- to β-cell conversion, we utilized transgenic mice expressing yellow fluorescent protein behind the proglucagon gene promoter (Gcg-Cre/YFP) and collected pancreata for histology at various gestational timepoints. Alpha-cell proliferation increased significantly at gestational day (GD) 9.5 in control pregnancies resulting in an increased ACM at GD18.5, and this was significantly reduced in LP animals. Despite these changes, serum glucagon was higher in LP mice at GD18.5. Pregnant Gcg-Cre/YFP mice showed no increase in the abundance of insulin+YFP+glucagon– cells (phenotypic β-cells). A second population of insulin+YFP+glucagon+ cells was identified which also did not alter during pregnancy. However, there was an altered anatomical distribution within islets with fewer insulin+YFP+glucagon– cells but more insulin+YFP+glucagon+ cells being present in the islet mantle at GD18.5. These findings demonstrate that dynamic changes in ACM occur during normal pregnancy and were altered in glucose-intolerant pregnancies.

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.

scholarly journals The Relationship between Membrane Potential and Calcium Dynamics in Glucose-Stimulated Beta Cell Syncytium in Acute Mouse Pancreas Tissue Slices

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e82374 ◽  
Author(s):  
Jurij Dolenšek ◽  
Andraž Stožer ◽  
Maša Skelin Klemen ◽  
Evan W. Miller ◽  
Marjan Slak Rupnik
Keyword(s):  
Membrane Potential ◽  
Beta Cell ◽  
Calcium Dynamics ◽  
Tissue Slices ◽  
Mouse Pancreas ◽  
The Relationship

scholarly journals Glucose-dependent activation, activity, and deactivation of beta cell networks in acute mouse pancreas tissue slices

2021 ◽  
Author(s):  
Andraz Stozer ◽  
Maša Skelin Klemen ◽  
Marko Gosak ◽  
Lidija Križančić Bombek ◽  
Viljem Pohorec ◽  
...  
Keyword(s):  
Beta Cell ◽  
Common Ground ◽  
Calcium Oscillations ◽  
Tissue Slices ◽  
Mouse Pancreas ◽  
Functional Connections ◽  
Wide Range ◽  
Network Properties ◽  
Beta Cell Heterogeneity ◽  
Cell Networks

Many details of glucose-stimulated intracellular calcium changes in beta cells during activation, activity, and deactivation, as well as their concentration-dependence, remain to be analyzed. Classical physiological experiments indicated that in islets, functional differences between individual cells are largely attenuated, but recent findings suggest considerable intercellular heterogeneity, with some cells possibly coordinating the collective responses. To address the above with an emphasis on heterogeneity and describing the relations between classical physiological and functional network properties, we performed functional multicellular calcium imaging in mouse pancreas tissue slices over a wide range of glucose concentrations. During activation, delays to activation of cells and any-cell-to-first-responder delays shortened, and the sizes of simultaneously responding clusters increased with increasing glucose. Exactly the opposite characterized deactivation. The frequency of fast calcium oscillations during activity increased with increasing glucose up to 12 mM glucose, beyond which oscillation duration became longer, resulting in a homogenous increase in active time. In terms of functional connectivity, islets progressed from a very segregated network to a single large functional unit with increasing glucose. A comparison between classical physiological and network parameters revealed that the first-responders during activation had longer active times during plateau and the most active cells during the plateau tended to deactivate later. Cells with the most functional connections tended to activate sooner, have longer active times, and deactivate later. Our findings provide a common ground for recent differing views on beta cell heterogeneity and an important baseline for future studies of stimulus-secretion and intercellular coupling.

scholarly journals Glucose-dependent activation, activity, and deactivation of beta cell networks in acute mouse pancreas tissue slices

2020 ◽  
Author(s):  
Jurij Dolenšek ◽  
Maša Skelin Klemen ◽  
Marko Gosak ◽  
Lidija Križančić-Bombek ◽  
Viljem Pohorec ◽  
...  
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Calcium Oscillations ◽  
Tissue Slices ◽  
Mouse Pancreas ◽  
Network Parameters ◽  
Cell Networks ◽  
Glucose Dependence

AbstractGlucose progressively stimulates insulin release over a wide range of concentrations. However, the nutrient coding underlying activation, activity, and deactivation of beta cells affecting insulin release remains only partially described. Experimental data indicate that nutrient sensing in coupled beta cells in islets is predominantly a collective trait, overriding to a large extent functional differences between cells. However, some degree of heterogeneity between coupled beta cells may play important roles. To further elucidate glucose-dependent modalities in coupled beta cells, the degree of functional heterogeneity, and uncover the emergent collective operations, we combined acute mouse pancreas tissue slices with functional multicellular calcium imaging. We recorded beta cell calcium responses from threshold (7 mM) to supraphysiological (16 mM) glucose concentrations with high spatial and temporal resolution. This enabled the analysis of both classical physiological parameters and complex network parameters, as well as their comparison at the level of individual cells. The activation profile displayed two major glucose concentration-dependent features, shortening of delays to initial activation, and shortening of delays until half activation with increasing glucose concentration. Inversely, during deactivation both delays to initial deactivation and until half deactivation were progressively longer with increasing glucose concentration. The plateau activity with fast calcium oscillations expressed two types of glucose-dependence. Physiological concentrations mostly affected the frequency of oscillations, whereas supraphysiological concentrations progressively prolonged the duration of oscillations. Most of the measured functional network parameters also showed clear glucose-dependence. In conclusion, we propose novel understanding for glucose-dependent coding properties in beta cell networks, and its deciphering may have repercussions for our understanding of the normal physiology of glucose homeostasis as well as of disturbances of metabolic homeostasis, such as diabetes mellitus.

scholarly journals TCF7L2 promotes beta cell regeneration in human and mouse pancreas

Diabetologia ◽  
2012 ◽  
Vol 55 (12) ◽  
pp. 3296-3307 ◽  
Author(s):  
L. Shu ◽  
K. Zien ◽  
G. Gutjahr ◽  
J. Oberholzer ◽  
F. Pattou ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Regeneration ◽  
Mouse Pancreas ◽  
Beta Cell Regeneration ◽  
Human And Mouse

scholarly journals Positive Effects of NPY1 Receptor Activation on Islet Structure Are Driven by Pancreatic Alpha- and Beta-Cell Transdifferentiation in Diabetic Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Ryan A. Lafferty ◽  
Neil Tanday ◽  
R. Charlotte Moffett ◽  
Frank Reimann ◽  
Fiona M. Gribble ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Mass ◽  
Cell Lineage ◽  
Beta Cell Mass ◽  
Receptor Activation ◽  
Alpha Cell ◽  
Alpha Cells ◽  
Positive Effects ◽  
Diabetes Status ◽  
Cell Conversion

Enzymatically stable and specific neuropeptide Y1 receptor (NPYR1) agonists, such as sea lamprey PYY(1-36) (SL-PYY(1-36)), are believed to improve glucose regulation in diabetes by targeting pancreatic islets. In this study, streptozotocin (STZ) diabetic transgenic GluCreERT2;ROSA26-eYFP and Ins1Cre/+;Rosa26-eYFP mouse models have been used to study effects of sustained NPYR1 activation on islet cell composition and alpha- and beta-cell lineage transitioning. STZ induced a particularly severe form of diabetes in Ins1Cre/+;Rosa26-eYFP mice, but twice-daily administration (25 nmol/kg) of SL-PYY(1-36) for 11 days consistently improved metabolic status. Blood glucose was decreased (p < 0.05 - p < 0.001) and both fasted plasma and pancreatic insulin significantly increased by SL-PYY(1-36). In both GluCreERT2;ROSA26-eYFP and Ins1Cre/+; Rosa26-eYFP mice, STZ provoked characteristic losses (p < 0.05 - p < 0.001) of islet numbers, beta-cell and pancreatic islet areas together with increases in area and central islet location of alpha-cells. With exception of alpha-cell area, these morphological changes were fully, or partially, returned to non-diabetic control levels by SL-PYY(1-36). Interestingly, STZ apparently triggered decreased (p < 0.001) alpha- to beta-cell transition in GluCreERT2;ROSA26-eYFP mice, together with increased loss of beta-cell identity in Ins1Cre/+;Rosa26-eYFP mice, but both effects were significantly (p < 0.001) reversed by SL-PYY(1-36). SL-PYY(1-36) also apparently reduced (p < 0.05) beta- to alpha-cell conversion in Ins1Cre/+;Rosa26-eYFP mice and glucagon expressing alpha-cells in GluCreERT2;ROSA26-eYFP mice. These data indicate that islet benefits of prolonged NPY1R activation, and especially restoration of beta-cell mass, are observed irrespective of diabetes status, being linked to cell lineage alterations including transdifferentiation of alpha- to beta-cells.

scholarly journals Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas

Development ◽  
2000 ◽  
Vol 127 (24) ◽  
pp. 5533-5540 ◽  
Author(s):  
M. Sander ◽  
L. Sussel ◽  
J. Conners ◽  
D. Scheel ◽  
J. Kalamaras ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Beta Cell ◽  
Beta Cells ◽  
Double Mutant ◽  
Cell Formation ◽  
Homeobox Gene ◽  
Secondary Transition ◽  
Major Pathway ◽  
Mouse Pancreas ◽  
Islet Development

Most insulin-producing beta-cells in the fetal mouse pancreas arise during the secondary transition, a wave of differentiation starting at embryonic day 13. Here, we show that disruption of homeobox gene Nkx6.1 in mice leads to loss of beta-cell precursors and blocks beta-cell neogenesis specifically during the secondary transition. In contrast, islet development in Nkx6. 1/Nkx2.2 double mutant embryos is identical to Nkx2.2 single mutant islet development: beta-cell precursors survive but fail to differentiate into beta-cells throughout development. Together, these experiments reveal two independently controlled pathways for beta-cell differentiation, and place Nkx6.1 downstream of Nkx2.2 in the major pathway of beta-cell differentiation.

Intraisiet somatostatin inhibits insulin secretion via SSTR5 in the isolated perfused mouse pancreas model

2001 ◽  
Vol 120 (5) ◽  
pp. A133-A133
Author(s):  
T TIRONE ◽  
S MOLDOVAN ◽  
M NORMAL ◽  
F DEMAYO ◽  
F CHARLESBRUNICARDI
Keyword(s):  
Insulin Secretion ◽  
Mouse Pancreas
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