scholarly journals Protection factors used to improve in vivo islet function

2021 ◽  
pp. 100051
Author(s):  
A. Margarida Carvalho ◽  
Omar Paulino da Silva Filho ◽  
Aart van Apeldoorn
Keyword(s):  
Islet Function

Improvement of Pig Islet Function by In Vivo Pancreatic Tissue Remodeling: A “Human-Like” Pig Islet Structure with Streptozotocin Treatment

2013 ◽  
Vol 22 (11) ◽  
pp. 2161-2173 ◽  
Author(s):  
Sophie Vériter ◽  
Najima Aouassar ◽  
Gwen Beaurin ◽  
Rose-Marie Goebbels ◽  
Pierre Gianello ◽  
...  
Keyword(s):  
Tissue Remodeling ◽  
Pancreatic Tissue ◽  
Islet Function

scholarly journals Loss-of-Function Mutation of the Galanin Gene Is Associated with Perturbed Islet Function in Mice

Endocrinology ◽  
2004 ◽  
Vol 145 (7) ◽  
pp. 3190-3196 ◽  
Author(s):  
Bo Ahrén ◽  
Giovanni Pacini ◽  
David Wynick ◽  
Nils Wierup ◽  
Frank Sundler
Keyword(s):  
Insulin Secretion ◽  
Islet Cells ◽  
Insulin Response ◽  
Tolerance Test ◽  
Glucose Disposal ◽  
Islet Function ◽  
Loss Of Function ◽  
Euglycemic Hyperinsulinemic Clamp

Abstract The neuropeptide galanin is expressed in sympathetic nerve terminals that surround islet cells and inhibits insulin secretion. To explore its role for islet function, we studied mice with a loss-of-function mutation in the galanin gene [galanin knockout (KO) mice]. Intravenous 2-deoxy-glucose, which activates both the sympathetic and parasympathetic branches of the autonomic nervous system, caused an initial (1–5 min) inhibition of insulin secretion that was impaired in galanin KO mice (P = 0.027), followed by a subsequent stimulation of insulin secretion that was augmented in galanin KO mice (P < 0.01). Similar effects were seen after chemical sympathectomy by 6-hydroxydopamine. In contrast, galanin KO mice had a reduced insulin response to glucose, both in vivo (P < 0.001) and in isolated islets (P < 0.001), and to arginine, both in vivo (P = 0.012) and in vitro (P = 0.018). During an iv glucose tolerance test, galanin KO mice had impaired glucose disposal (P = 0.005) due to a reduced insulin response (P < 0.001) and a reduced insulin-independent glucose elimination (glucose effectiveness; P = 0.040). Insulin sensitivity, as judged by a euglycemic, hyperinsulinemic clamp technique, was slightly increased in galanin KO mice (P = 0.032). We conclude that 1) galanin may contribute to sympathetic influences inhibiting insulin secretion in mice, and 2) galanin KO mice have a reduced glucose-induced insulin secretion.

IN VITRO AND IN VIVO OVER-INDUCTION OF AUTOPHAGY IN PANCREATIC ISLETS BY RAPAMYCIN AND IMPAIRS ISLET FUNCTION

2010 ◽  
Vol 90 ◽  
pp. 372
Author(s):  
M. Tanemura ◽  
Y. Ohmura ◽  
T. Machida ◽  
T. Deguchi ◽  
H. Wada ◽  
...  
Keyword(s):  
Pancreatic Islets ◽  
Islet Function

scholarly journals In vivo vascularization and islet function in a microwell device for pancreatic islet transplantation

2021 ◽  
Author(s):  
Alexandra M. Smink ◽  
Katarzyna Skrzypek ◽  
Jolanda Visser ◽  
Rei Kuwabara ◽  
Bart J. de Haan ◽  
...  
Keyword(s):  
Islet Transplantation ◽  
Pancreatic Islet ◽  
Islet Function ◽  
Pancreatic Islet Transplantation

scholarly journals Morphological and Functional Studies on Submucosal Islet Transplants in Normal and Diabetic Hamsters

2002 ◽  
Vol 11 (6) ◽  
pp. 529-537 ◽  
Author(s):  
Nikolay Tchervenivanov ◽  
Songyang Yuan ◽  
Mark Lipsett ◽  
Despina Agapitos ◽  
Lawrence Rosenberg
Keyword(s):  
Positive Impact ◽  
Large Animal Model ◽  
Large Animal ◽  
Islet Function ◽  
Term Outcome ◽  
Intravenous Glucose ◽  
K Value ◽  
Long Term Outcome ◽  
Islet Transplants

The long-term outcome of human islet allotransplantation is poor, and it remains to be seen if the Edmonton Protocol will make a positive impact upon the extension of posttransplant islet function. Hence, establishing an implantation site capable of sustaining islet allografts for a prolonged duration needs to be explored. In this study we investigated the submucosal space of the duodenum in Syrian golden hamsters. Following transplantation of more than 800 islets into streptozotocin (STZ)-induced diabetic hamsters, basal nonfasted blood glucose levels decreased from 403 ± 14 to 143 ± 10 mg/dl within 5 weeks posttransplantation. In these animals, in vivo islet function, as determined by intravenous glucose tolerance test (IVGTT), was similar to nondiabetic controls (K values: 1.16 ± 0.12 vs. 0.95 ± 0.06, respectively) and was significantly greater than diabetic controls (K value: 0.47 ± 0.07). Islets transplanted into the submucosal space become richly vascularized within 2 weeks, and there is minimal host inflammatory infiltrate. The β-cells of the graft remain well granulated with insulin for at least 129 days. We conclude that the submucosal space is an effective engraftment site for islets that warrants further development in a large-animal model.

scholarly journals Change in Viability and Function of Pancreatic Islets after Coculture with Mesenchymal Stromal Cells: A Systemic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xiaohang Li ◽  
Hongxin Lang ◽  
Baifeng Li ◽  
Chengshuo Zhang ◽  
Ning Sun ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Fasting Blood Glucose ◽  
Insulin Level ◽  
Systemic Review ◽  
Islet Function ◽  
Clinical Islet Transplantation

Background. There is no clear consensus on the effect of coculture of islets with mesenchymal stem cells (MSCs) on islet function and viability. Methods. We conducted a meta-analysis of relevant studies to evaluate the effect of coculture of islets with MSCs on the function and viability of islets, both in vitro and in vivo. We searched PubMed, Embase, and Web of Science databases for all relevant studies that compared the effect of coculture of islets with MSCs on the function and viability of islets (language of publication: English; reference period: January 2000–May 2019). Data pertaining to islet function and viability, concentrations of some cytokines, and in vivo experimental outcomes were extracted and compared. Results. Twenty-four articles were included in the meta-analysis. In comparison to islets cultured alone, coculture of islets with MSCs was associated with a significantly higher islet viability [weighted mean difference (WMD), -15.59; -22.34 to -8.83; P<0.00001], insulin level (WMD, -5.74; -9.29 to -2.19; P=0.002), insulin secretion index (WMD, -2.45; -3.70 to -1.21; P=0.0001), and higher concentrations of interleukin-6 (WMD, -1225.66; -2044.47 to -406.86; P=0.003) and vascular endothelial growth factor (WMD, -1.19; -2.25 to -0.14; P=0.03). Direct coculture of islets and MSCs significantly increased islet viability (WMD, -19.82; -26.56 to -13.07; P<0.00001). In the in vivo experiments, coculture of islets with MSCs induced lower fasting blood glucose level (on postoperative days 21 and 28, WMD, 102.60; 27.14 to 178.05; P=0.008 and WMD, 121.19; 49.56 to 192.82; P=0.0009) and better glucose tolerance (blood glucose at 30 minutes after intraperitoneal injection of glucose, WMD, 85.92; 5.33 to 166.51; P=0.04). Conclusion. Coculture of islets with MSCs improves insulin secretory function of islets and enhances islet viability. Direct coculture of two cells significantly increased islet viability. MSC-based strategy may be beneficial for clinical islet transplantation for type 1 diabetes in the future.

scholarly journals Human Adipose-Derived Mesenchymal Stem Cells Respond to Short-Term Hypoxia by Secreting Factors Beneficial for Human Islets in Vitro and Potentiate Antidiabetic Effect in Vivo

Cell Medicine ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 103-116 ◽  
Author(s):  
Simen W. Schive ◽  
Mohammad Reza Mirlashari ◽  
Grete Hasvold ◽  
Mengyu Wang ◽  
Dag Josefsen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Islets ◽  
Insulin Content ◽  
Oral Glucose ◽  
Islet Function ◽  
Soluble Factors ◽  
Antidiabetic Effect

Adipose-derived mesenchymal stem cells (ASCs) release factors beneficial for islets in vitro and protect against hyperglycemia in rodent models of diabetes. Oxygen tension has been shown to induce metabolic changes and alter ASCs' release of soluble factors. The effects of hypoxia on the antidiabetic properties of ASCs have not been explored. To investigate this, we incubated human ASCs for 48 h in 21% (normoxia) or 1% O2 (hypoxia) and compared viability, cell growth, surface markers, differentiation capability, and soluble factors in the conditioned media (CM). Human islets were exposed to CM from ASCs incubated in either normoxia or hypoxia, and islet function and apoptosis after culture with or without proinflammatory cytokines were measured. To test hypoxic preconditioned ASCs' islet protective effects in vivo, ASCs were incubated for 48 h in normoxia or hypoxia before being injected into Balb/c Rag 1-/- immunodeficient mice with streptozotocin-induced insulitis. Progression of diabetes and insulin content of pancreas were measured. We found that incubation in hypoxia was well tolerated by ASCs and that levels of VEGF-A, FGF-2, and bNGF were elevated in CM from ASCs incubated in hypoxia compared to normoxia, while levels of HGF, IL-8, and CXCL1 were reduced. CM from ASCs incubated in hypoxia significantly improved human islet function and reduced apoptosis after culture, and reduced cytokine-induced apoptosis. In our mouse model, pancreas insulin content was higher in both groups receiving ASCs compared to control, but the mice receiving preconditioned ASCs had lower random and fasting blood glucose, as well as improved oral glucose tolerance compared to untreated mice. In conclusion, our in vitro results indicate that the islet protective potential of ASCs improves in hypoxia, and we give insight into factors involved in this. Finally we show that hypoxic preconditioning potentiates ASCs' antidiabetic effect in vivo.

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