scholarly journals Non-invasive monitoring of glycemia-induced regulation of GLP-1R expression in murine and human islets of langerhans

2020 ◽  
Author(s):  
Ada Admin ◽  
Mijke Buitinga ◽  
Christian M.Cohrs ◽  
Wael A.Eter ◽  
Lieke Claessens-Joosten ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Human Islets ◽  
Tracer Uptake ◽  
Expression Levels ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Islet Volume

GLP-1R imaging with radiolabelled exendin has proven to be a powerful tool to quantify beta-cell mass (BCM) <i>in vivo</i>. As GLP-1R expression is thought to be influenced by glycemic control, we examined the effect of blood glucose levels on GLP-1R-mediated exendin uptake in both murine and human islets and its implications for BCM quantification. Periods of hyperglycemia significantly reduced exendin uptake in murine and human islets, which was paralleled by a reduction in GLP-1R expression. Detailed mapping of the tracer uptake and insulin and GLP-1R expression conclusively demonstrated that the observed reduction in tracer uptake directly correlates to GLP-1R expression levels. Importantly, the linear correlation between tracer uptake and beta-cell area was maintained in spite of the reduced GLP-1R expression levels. Subsequent normalization of blood glucose levels restored absolute tracer uptake and GLP-1R expression in beta-cells and the observed loss in islet volume was halted. <p>This manuscript emphasizes the potency of nuclear imaging techniques to monitor receptor regulation non-invasively. Our findings have significant implications for clinical practice, indicating that blood glucose levels should be near-normalized for at least three weeks prior to GLP-1R agonist treatment or quantitative radiolabeled exendin imaging for BCM analysis.</p>

scholarly journals Non-invasive monitoring of glycemia-induced regulation of GLP-1R expression in murine and human islets of langerhans

2020 ◽  
Author(s):  
Ada Admin ◽  
Mijke Buitinga ◽  
Christian M.Cohrs ◽  
Wael A.Eter ◽  
Lieke Claessens-Joosten ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Human Islets ◽  
Tracer Uptake ◽  
Expression Levels ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Islet Volume

GLP-1R imaging with radiolabelled exendin has proven to be a powerful tool to quantify beta-cell mass (BCM) <i>in vivo</i>. As GLP-1R expression is thought to be influenced by glycemic control, we examined the effect of blood glucose levels on GLP-1R-mediated exendin uptake in both murine and human islets and its implications for BCM quantification. Periods of hyperglycemia significantly reduced exendin uptake in murine and human islets, which was paralleled by a reduction in GLP-1R expression. Detailed mapping of the tracer uptake and insulin and GLP-1R expression conclusively demonstrated that the observed reduction in tracer uptake directly correlates to GLP-1R expression levels. Importantly, the linear correlation between tracer uptake and beta-cell area was maintained in spite of the reduced GLP-1R expression levels. Subsequent normalization of blood glucose levels restored absolute tracer uptake and GLP-1R expression in beta-cells and the observed loss in islet volume was halted. <p>This manuscript emphasizes the potency of nuclear imaging techniques to monitor receptor regulation non-invasively. Our findings have significant implications for clinical practice, indicating that blood glucose levels should be near-normalized for at least three weeks prior to GLP-1R agonist treatment or quantitative radiolabeled exendin imaging for BCM analysis.</p>

scholarly journals Possible relationship between changes in islet neogenesis and islet neogenesis-associated protein-positive cell mass induced by sucrose administration to normal hamsters

2000 ◽  
Vol 165 (3) ◽  
pp. 725-733 ◽  
Author(s):  
H Del Zotto ◽  
L Massa ◽  
R Rafaeloff ◽  
GL Pittenger ◽  
A Vinik ◽  
...  
Keyword(s):  
Beta Cell ◽  
Endocrine Pancreas ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Serum Glucose ◽  
Islet Neogenesis ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Ductal Cells ◽  
Islet Volume

The possible relationship between changes in islet cell mass and in islet neogenesis-associated protein (INGAP)-cell mass induced by sucrose administration to normal hamsters was investigated. Normal hamsters were given sucrose (10% in drinking water) for 5 (S8) or 21 (S24) weeks and compared with control (C) fed hamsters. Serum glucose and insulin levels were measured and quantitative immunocytochemistry of the endocrine pancreas was performed. Serum glucose levels were comparable among the groups, while insulin levels were higher in S hamsters. There was a significant increase in beta-cell mass (P<0.02) and in beta-cell 5-bromo-2'-deoxyuridine index (P<0.01), and a significant decrease in islet volume (P<0.01) only in S8 vs C8 hamsters. Cytokeratin (CK)-labelled cells were detected only in S8 hamsters. INGAP-positive cell mass was significantly larger only in S8 vs C8 hamsters. Endocrine INGAP-positive cells were located at the islet periphery ( approximately 96%), spread within the exocrine pancreas ( approximately 3%), and in ductal cells (<1%) in all groups. INGAP positivity and glucagon co-localization varied according to topographic location and type of treatment. In C8 hamsters, 49.1+/-6. 9% cells were INGAP- and glucagon-positive in the islets, while this percentage decreased by almost half in endocrine extra-insular and ductal cells. In S8 animals, co-expression increased in endocrine extra-insular cells to 36.3+/-9.5%, with similar figures in the islets, decreasing to 19.7+/-6.9% in ductal cells. INGAP-positive cells located at the islet periphery also co-expressed CK. In conclusion, a significant increase of INGAP-positive cell mass was only observed at 8 weeks when neogenesis was present, suggesting that this peptide might participate in the control of islet neogenesis. Thus, INGAP could be a potentially useful tool to treat conditions in which there is a decrease in beta-cell mass.

scholarly journals The p21-activated kinase (PAK1) is involved in diet-induced beta cell mass expansion and survival in mice and human islets

Diabetologia ◽  
2016 ◽  
Vol 59 (10) ◽  
pp. 2145-2155 ◽  
Author(s):  
Miwon Ahn ◽  
Stephanie M. Yoder ◽  
Zhanxiang Wang ◽  
Eunjin Oh ◽  
Latha Ramalingam ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Human Islets ◽  
P21 Activated Kinase ◽  
Mass Expansion

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.

A SELECTIVE DECREASE IN THE BETA CELL MASS OF HUMAN ISLETS TRANSPLANTED INTO DIABETIC NUDE MICE

1995 ◽  
Vol 59 (6) ◽  
pp. 817-820 ◽  
Author(s):  
A. M. DAVALLI ◽  
Y. OGAWA ◽  
C. RICORDI ◽  
D. W. SCHARP ◽  
S. BONNER-WEIR ◽  
...  
Keyword(s):  
Beta Cell ◽  
Nude Mice ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Human Islets

scholarly journals Study of the Mechanism Underlying the Onset of Diabetic Xeroderma Focusing on an Aquaporin-3 in a Streptozotocin-Induced Diabetic Mouse Model

2019 ◽  
Vol 20 (15) ◽  
pp. 3782 ◽  
Author(s):  
Nobutomo Ikarashi ◽  
Nanaho Mizukami ◽  
Risako Kon ◽  
Miho Kaneko ◽  
Ryogo Uchino ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Water Transport ◽  
Diabetic Mouse ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Aquaporin 3 ◽  
Expression Levels ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Site Binding

Xeroderma is a frequent complication in diabetic patients. In this study, we investigated the mechanism underlying the onset of diabetic xeroderma, focusing on aquaporin-3 (AQP3), which plays an important role in water transport in the skin. Dermal water content in diabetic mice was significantly lower than that in control mice. The expression level of AQP3 in the skin was significantly lower in diabetic mice than in control mice. One week after streptozotocin (STZ) treatment, despite their increased blood glucose levels, mice showed no changes in the expression levels of AQP3, Bmal1, Clock, and D site-binding protein (Dbp) in the skin and 8-hydroxydeoxyguanosine (8-OHdG) in the urine. In contrast, two weeks after STZ treatment, mice showed increases in the blood glucose level, decreases in AQP3, Bmal1, Clock, and Dbp levels, and increases in the urinary levels of 8-OHdG. The results of this study suggest that skin AQP3 expression decreases in diabetes, which may limit water transport from the vessel side to the corneum side, causing dry skin. In addition, in diabetic mice, increased oxidative stress triggered decreases in the expression levels of Bmal1 and Clock in the skin, thereby inhibiting the transcription of Aqp3 by Dbp, which resulted in decreased AQP3 expression.

Exendin-4 Decreases Blood Glucose Levels, but Does not Affect Other Metabolic Parameters in Transplanted Human Islets from Old and Young Donors

2012 ◽  
Vol 94 (10S) ◽  
pp. 703
Author(s):  
A. Sahraoui ◽  
M. Hoeyem ◽  
D. M. Smith ◽  
L. A. Johansson ◽  
O. Korsgren ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Human Islets ◽  
Metabolic Parameters ◽  
Glucose Levels ◽  
Blood Glucose Levels

scholarly journals miRNA-375 a Sensor of Glucotoxicity Is Altered in the Serum of Children with Newly Diagnosed Type 1 Diabetes

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Lucien Marchand ◽  
Audrey Jalabert ◽  
Emmanuelle Meugnier ◽  
Kathleen Van den Hende ◽  
Nicole Fabien ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Human Islets ◽  
Rt Pcr ◽  
Stem Loop ◽  
Cell Alterations ◽  
Established Role

Background.The use of miRNAs as biomarkers for Type 1 Diabetes (T1D) risk is attractive as T1D is usually diagnosed in front of acute symptoms. As miR-375 is highly expressed in the endocrine pancreas, we postulated that its circulating level might reflect beta cell alterations and might be altered in the blood of T1D patients recently diagnosed.Methods.Sera were obtained from 22 T1D children at onset of the disease, before subcutaneous insulin treatment, and from 10 nondiabetic pediatric controls. MiR-375 seric level was quantified by stem-loop RT-PCR-based assay. MiRNAs regulations in isolated human islets in response to high glucose concentrations were determined by TaqMan Low-Density Array.Results.The abundance of miR-375, among the 410 miRNAs detected in human islets, mirrored its well-established role in rodent islet biology. Upregulated miRNAs targeted genes involved in islet homeostasis and regulation of beta cell mass. Downregulated miRNAs, including miR-375, were involved in pancreas secretion and protein turnover. Seric level of miR-375 was lower in T1D children versus age-matched controls, without any correlations with HbA1c, glycaemia, and number of autoantibodies.Conclusion.Altered circulating level of miR-375 at onset of T1D might be a general biomarker of metabolic alterations and inflammation associated with the disease.

A SELECTIVE DECREASE IN THE BETA CELL MASS OF HUMAN ISLETS TRANSPLANTED INTO DIABETIC NUDE MICE

1995 ◽  
Vol 59 (6) ◽  
pp. 817-820 ◽  
Author(s):  
A. M. DAVALLI ◽  
Y. OGAWA ◽  
C. RICORDI ◽  
D. W. SCHARP ◽  
S. BONNER-WEIR ◽  
...  
Keyword(s):  
Beta Cell ◽  
Nude Mice ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Human Islets
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