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 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 Mechanisms involved in the beta-cell mass increase induced by chronic sucrose feeding to normal rats

2002 ◽  
Vol 174 (2) ◽  
pp. 225-231 ◽  
Author(s):  
H Del Zotto ◽  
CL Gomez Dumm ◽  
S Drago ◽  
A Fortino ◽  
GC Luna ◽  
...  
Keyword(s):  
Body Weight ◽  
Beta Cell ◽  
Beta Cells ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Serum Glucose ◽  
Beta Cell Apoptosis ◽  
Cell Replication ◽  
Replication Rate ◽  
Endocrine Tissue

The aim of the present study was to clarify the mechanisms by which a sucrose-rich diet (SRD) produces an increase in the pancreatic beta-cell mass in the rat. Normal Wistar rats were fed for 30 weeks either an SRD (SRD rats; 63% wt/wt), or the same diet but with starch instead of sucrose in the same proportion (CD rats). We studied body weight, serum glucose and triacylglycerol levels, endocrine tissue and beta-cell mass, beta-cell replication rate (proliferating cell nuclear antigen; PCNA), islet neogenesis (cytokeratin immunostaining) and beta-cell apoptosis (propidium iodide). Body weight (g) recorded in the SRD rats was significantly (P<0.05) larger than that of the CD group (556.0+/-8.3 vs 470.0+/-13.1). Both serum glucose and triacylglycerol levels (mmol/l) were also significantly higher (P<0.05) in SRD than in CD rats (serum glucose, 8.11+/-0.14 vs 6.62+/-0.17; triacylglycerol, 1.57+/-0.18 vs 0.47+/-0.04). The number of pancreatic islets per unit area increased significantly (P<0.05) in SRD rats (3.29+/-0.1 vs 2.01+/-0.2). A significant increment (2.6 times) in the mass of endocrine tissue was detected in SRD animals, mainly due to an increase in the beta-cell mass (P=0.0025). The islet cell replication rate, measured as the percentage of PCNA-labelled beta cells increased 6.8 times in SRD rats (P<0.03). The number of apoptotic cells in the endocrine pancreas decreased significantly (three times) in the SRD animals (P=0.03). The cytokeratin-positive area did not show significant differences between CD and SRD rats. The increase of beta-cell mass induced by SRD was accomplished by an enhanced replication of beta cells together with a decrease in the rate of beta-cell apoptosis, without any evident participation of islet neogenesis. This pancreatic reaction was unable to maintain serum glucose levels of these rats at the level measured in CD animals.

Current Progress in Non-Invasive Imaging of Beta Cell Mass of the Endocrine Pancreas

2006 ◽  
Vol 13 (23) ◽  
pp. 2761-2773 ◽  
Author(s):  
Fabiola Souza ◽  
Matthew Freeby ◽  
Kristi Hultman ◽  
Norman Simpson ◽  
Alan Herron ◽  
...  
Keyword(s):  
Beta Cell ◽  
Endocrine Pancreas ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Non Invasive

scholarly journals Dysregulation of Dicer1 in Beta Cells Impairs Islet Architecture and Glucose Metabolism

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Amitai D. Mandelbaum ◽  
Tal Melkman-Zehavi ◽  
Roni Oren ◽  
Sharon Kredo-Russo ◽  
Tomer Nir ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Beta Cell ◽  
Beta Cells ◽  
Endocrine Pancreas ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Pancreas Development ◽  
Wild Type ◽  
Insulin Expression ◽  
E Cadherin

microRNAs (miRNAs) play important roles in pancreas development and in regulation of insulin expression in the adult. Here we show that loss of miRNAs activity in beta-cells during embryonic development results in lower beta-cell mass and in impaired glucose tolerance. Dicer1-null cells initially constitute a significant portion of the total beta-cell population. However, during postnatal development, Dicer1-null cells are depleted. Furthermore, wild-type beta cells are repopulating the islets in complex compensatory dynamics. Because loss of Dicer1 is also associated with changes in the distribution of membranous E-cadherin, we hypothesized that E-cadherin activity may play a role in beta cell survival or islet architecture. However, genetic loss of E-cadherin function does not impair islet architecture, suggesting that miRNAs likely function through other or redundant effectors in the endocrine pancreas.

scholarly journals Pancreatic duodenal homeobox-1 and islet neogenesis-associated protein: a possible combined marker of activateable pancreatic cell precursors

2003 ◽  
Vol 177 (2) ◽  
pp. 249-259 ◽  
Author(s):  
JJ Gagliardino ◽  
H Del Zotto ◽  
L Massa ◽  
LE Flores ◽  
MI Borelli
Keyword(s):  
Beta Cell ◽  
Early Stage ◽  
Cell Mass ◽  
Protein A ◽  
Beta Cell Mass ◽  
Cell Subpopulation ◽  
Pancreatic Cell ◽  
Islet Neogenesis ◽  
Stage Of Development

The aim of this work was to study the possible relationship between pancreatic duodenal homeobox-1 (Pdx-1) and islet neogenesis-associated protein (INGAP) during induced islet neogenesis. Pregnant hamsters were fed with (S) and without (C) sucrose, and glycemia, insulin secretion in vitro, and pancreas immunomorphometric parameters were measured in their 7-day-old offspring. S offspring had significantly lower glycemic levels than C animals. Insulin release in response to increasing glucose concentrations in the incubation medium (2-16 mM glucose) did not increase in pancreata from either C or S offspring. However, pancreata from S offspring released more insulin than those from C animals. In S offspring, beta-cell mass, beta-cell replication rate and islet neogenesis increased significantly, with a simultaneous decrease in beta-cell apoptotic rate. INGAP- and Pdx-1-positive cell mass also increased in the islets and among acinar and duct cells. We found two subpopulations of Pdx-1 cells: INGAP-positive and INGAP-negative. Pdx-1/INGAP-positive cells did not stain with insulin, glucagon, somatostatin, pancreatic polypeptide, or neurogenin 3 antibodies. The increment of Pdx-1/INGAP-positive cells represented the major contribution to the Pdx-1 cell mass increase. Such increments varied among pancreas subsectors: ductal>insular>extrainsular. Our results suggested that INGAP participates in the regulation of islet neogenesis, and Pdx-1/INGAP-positive cells represent a new stem cell subpopulation at an early stage of development, highly activateable in neogenesis.

scholarly journals Insulin-positive ductal cells do not migrate into preexisting islets during pregnancy

2021 ◽  
Author(s):  
Qun Liu ◽  
Yinan Jiang ◽  
Lingyan Zhu ◽  
Jieqi Qian ◽  
Chaoban Wang ◽  
...  
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Gene Expression Omnibus ◽  
Glucose Response ◽  
Ductal Cells ◽  
Duct Cells ◽  
And Migration

AbstractThe adult pancreatic ductal system was suggested to harbor facultative beta-cell progenitors similar to the embryonic pancreas, and the appearance of insulin-positive duct cells has been used as evidence for natural duct-to-beta-cell reprogramming. Nevertheless, the phenotype and fate of these insulin-positive cells in ducts have not been determined. Here, we used a cell-tagging dye, CFDA-SE, to permanently label pancreatic duct cells through an intraductal infusion technique. Representing a time when significant increases in beta-cell mass occur, pregnancy was later induced in these CFDA-SE-treated mice to assess the phenotype and fate of the insulin-positive cells in ducts. We found that a small portion of CFDA-SE-labeled duct cells became insulin-positive, but they were not fully functional beta-cells based on the in vitro glucose response and the expression levels of key beta-cell genes. Moreover, these insulin-positive cells in ducts expressed significantly lower levels of genes associated with extracellular matrix degradation and cell migration, which may thus prevent their budding and migration into preexisting islets. A similar conclusion was reached through analysis of the Gene Expression Omnibus database for both mice and humans. Together, our data suggest that the contribution of duct cells to normal beta-cells in adult islets is minimal at best.

scholarly journals Investigation of the preservation effect of canagliflozin on pancreatic beta cell mass using SPECT/CT imaging with 111In-labeled exendin-4

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Keita Hamamatsu ◽  
Hiroyuki Fujimoto ◽  
Naotaka Fujita ◽  
Takaaki Murakami ◽  
Masaharu Shiotani ◽  
...  
Keyword(s):  
Beta Cell ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Ct Imaging ◽  
Control Group ◽  
Imaging Method ◽  
Therapeutic Effects ◽  
Glucose Levels ◽  
Pancreatic Beta Cell Mass

AbstractRadiolabeled exendin derivatives are promising for non-invasive quantification of pancreatic beta cell mass (BCM); longitudinal observation of BCM for evaluation of therapeutic effects has not been achieved. The aim of this study is to demonstrate the usefulness of our developing method using [Lys12(111In-BnDTPA-Ahx)]exendin-4 to detect longitudinal changes in BCM. We performed a longitudinal study with obese type 2 diabetes model (db/db) mice administered canagliflozin, which is reported to preserve BCM. Six-week-old mice were assigned to a canagliflozin-administered group or a control group. Blood glucose levels of the canagliflozin group were significantly lower than those of the control group. Plasma insulin levels, insulin secretion during OGTT and insulin content in the pancreas were preserved in the canagliflozin group in comparison with those in the control group. According to SPECT/CT imaging analysis using [Lys12(111In-BnDTPA-Ahx)]exendin-4, pancreatic uptake was significantly decreased in the control group, whereas there was no significant change in the canagliflozin group. After nine weeks, both pancreatic uptake and BCM of the canagliflozin group were significantly higher than those of the control group, and a correlation between them was observed. In conclusion, our imaging method confirmed the BCM-preservation effect of canagliflozin, and demonstrated its potential for longitudinal evaluation of BCM.

scholarly journals A Pentadecapeptide Fragment of Islet Neogenesis-Associated Protein Increases Beta-Cell Mass and Reverses Diabetes in C57BL/6J Mice

2004 ◽  
Vol 240 (5) ◽  
pp. 875-884 ◽  
Author(s):  
Lawrence Rosenberg ◽  
Mark Lipsett ◽  
Ji-Won Yoon ◽  
Marc Prentki ◽  
Rennian Wang ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Islet Neogenesis

scholarly journals Systemic administration of pituitary adenylate cyclase-activating polypeptide maintains beta-cell mass and retards onset of hyperglycaemia in beta-cell-specific calmodulin-overexpressing transgenic mice

2005 ◽  
Vol 152 (5) ◽  
pp. 805-811 ◽  
Author(s):  
Shin Tsunekawa ◽  
Yoshitaka Miura ◽  
Naoki Yamamoto ◽  
Yuji Itoh ◽  
Yoh Ariyoshi ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Isolated Islets ◽  
Insulin Content ◽  
Islet Function ◽  
Primary Defect ◽  
Glucose Levels ◽  
Pituitary Adenylate Cyclase

Objective: Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to play an important role in the regulation of islet function. We investigated its effects in beta-cell-specific calmodulin-overexpressing diabetic (CaMTg) mice, in which we consider that apoptosis of beta cells is the primary defect leading to basal hyperglycaemia. Methods: CaMTg mice were treated with continuous s.c. infusions of PACAP from 2 to 4 weeks after birth, and were evaluated against littermate non-transgenic (nTg) and saline-treated CaMTg mice as to plasma glucose levels, insulin content, islet function and morphological features. Results: Remarkable and progressive hyperglycaemia was observed in CaMTg mice, and PACAP treatment blunted this elevation. Insulin secretion from isolated islets demonstrated an impaired response to glucose in CaMTg mice, and PACAP treatment did not cause any improvement. The total pancreatic insulin content in CaMTg mice decreased significantly to 19.1% of that in nTg mice. PACAP treatment of CaMTg mice increased the content to 158% of the value in saline-treated CaMTg mice. The insulin content in isolated islets from CaMTg mice also decreased to 15.9% of that in nTg mice, while PACAP treatment caused a doubling of the value. Immunohistochemical investigation revealed that the insulin-positive islet area was markedly smaller in CaMTg mice and that PACAP treatment significantly expanded the insulin-positive islet area. Conclusions: These findings indicate that PACAP treatment retards the onset of hyperglycaemia in CaMTg mice by maintaining beta-cell mass and PACAP treatment may potentially be a therapeutic measure for preventing beta-cell exhaustion during hyperglycaemia.

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