Effects of the Molecular Weight of Peg Molecules (8, 20 and 35 KDA) on Cell Function and Allograft Survival Prolongation in Pancreatic Islets Transplantation

2006 ◽  
Vol 38 (7) ◽  
pp. 2354-2355 ◽  
Author(s):  
Y. Neuzillet ◽  
S. Giraud ◽  
L. Lagorce ◽  
M. Eugene ◽  
P. Debre ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Pancreatic Islets ◽  
Cell Function ◽  
Allograft Survival ◽  
Survival Prolongation ◽  
Islets Transplantation

scholarly journals Functional Role of Serotonin in Insulin Secretion in a Diet-Induced Insulin-Resistant State

Endocrinology ◽  
2014 ◽  
Vol 156 (2) ◽  
pp. 444-452 ◽  
Author(s):  
Kyuho Kim ◽  
Chang-Myung Oh ◽  
Mica Ohara-Imaizumi ◽  
Sangkyu Park ◽  
Jun Namkung ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Cell Function ◽  
Β Cell ◽  
Pancreas Perfusion ◽  
Insulin Resistant ◽  
Β Cell Function ◽  
Resistant State ◽  
Insulin Resistant State

The physiological role of serotonin, or 5-hydroxytryptamine (5-HT), in pancreatic β-cell function was previously elucidated using a pregnant mouse model. During pregnancy, 5-HT increases β-cell proliferation and glucose-stimulated insulin secretion (GSIS) through the Gαq-coupled 5-HT2b receptor (Htr2b) and the 5-HT3 receptor (Htr3), a ligand-gated cation channel, respectively. However, the role of 5-HT in β-cell function in an insulin-resistant state has yet to be elucidated. Here, we characterized the metabolic phenotypes of β-cell-specific Htr2b−/− (Htr2b βKO), Htr3a−/− (Htr3a knock-out [KO]), and β-cell-specific tryptophan hydroxylase 1 (Tph1)−/− (Tph1 βKO) mice on a high-fat diet (HFD). Htr2b βKO, Htr3a KO, and Tph1 βKO mice exhibited normal glucose tolerance on a standard chow diet. After 6 weeks on an HFD, beginning at 4 weeks of age, both Htr3a KO and Tph1 βKO mice developed glucose intolerance, but Htr2b βKO mice remained normoglycemic. Pancreas perfusion assays revealed defective first-phase insulin secretion in Htr3a KO mice. GSIS was impaired in islets isolated from HFD-fed Htr3a KO and Tph1 βKO mice, and 5-HT treatment improved insulin secretion from Tph1 βKO islets but not from Htr3a KO islets. Tph1 and Htr3a gene expression in pancreatic islets was not affected by an HFD, and immunostaining could not detect 5-HT in pancreatic islets from mice fed an HFD. Taken together, these results demonstrate that basal 5-HT levels in β-cells play a role in GSIS through Htr3, which becomes more evident in a diet-induced insulin-resistant state.

Tumor necrosis factor activity of pancreatic islets

1997 ◽  
Vol 273 (2) ◽  
pp. E433-E437 ◽  
Author(s):  
S. K. Leeper-Woodford ◽  
B. W. Tobin
Keyword(s):  
Insulin Secretion ◽  
Tumor Necrosis Factor ◽  
Pancreatic Islets ◽  
Tumor Necrosis ◽  
Cell Function ◽  
Secretory Activity ◽  
Organ Injury ◽  
Pancreatic Islet Cell ◽  
Islet Cell Function ◽  
Necrosis Factor

Tumor necrosis factor (TNF) is involved in the pathogenesis of acute sepsis-induced organ injury and has been implicated as a mediator of metabolic alterations observed during sepsis. Pancreatic islet cell function may be significantly compromised during sepsis or endotoxemia, and sepsis also increases plasma levels of epinephrine, a modifier of islet insulin secretion. We proposed that islets exposed to bacterial lipopolysaccharide (LPS) produce TNF and that epinephrine attenuates islet secretory activity. We monitored the effects of LPS and epinephrine on TNF and insulin activity of isolated Wistar-Furth rat islets (pancreas digested with collagenase, islets isolated using Ficoll gradients; n = 4 islet populations, each with 632 +/- 11 islets/2.5 ml culture medium). Islets were incubated (37 degrees C, 5% CO2) 3 days. LPS (Escherichia coli, 1 microgram/ml) and epinephrine (14 micrograms/ml) were added to the islets, and incubations were continued for 1-4 h. Glucose (Beckman Glucose Analyzer), insulin (radioimmunoassay), and TNF (L929 cytotoxicity assay) were measured in the islet medium samples at 1- to 4-h time points. In the conditioned medium, glucose decreased (P < 0.05), insulin increased (P < 0.05), and exposure to LPS did not alter these levels [P = not significant (NS)] but did increase TNF activity by 400% (P < 0.05). Epinephrine reduced insulin by 38-43% (P < 0.05) and TNF by 20-25% (P < 0.05) but had no effect on glucose levels (P = NS). We conclude that insulin is secreted from isolated islets and that exposure to LPS acutely increases islet-derived TNF activity, whereas epinephrine modifies TNF and insulin secretion of rat pancreatic islets.

Potent Skin Allograft Survival Prolongation Using a Committed Progenitor Fraction of Bone Marrow in Mice

2004 ◽  
Vol 78 (3) ◽  
pp. 383-391 ◽  
Author(s):  
Edip Akpinar ◽  
Nancy Craighead ◽  
Douglas Smoot ◽  
Douglas A. Hale
Keyword(s):  
Bone Marrow ◽  
Allograft Survival ◽  
Skin Allograft ◽  
Survival Prolongation

scholarly journals Dexamethasone potentiates myeloid-derived suppressor cell function in prolonging allograft survival through nitric oxide

2014 ◽  
Vol 96 (5) ◽  
pp. 675-684 ◽  
Author(s):  
Jiongbo Liao ◽  
Xiao Wang ◽  
Yujing Bi ◽  
Bo Shen ◽  
Kun Shao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Function ◽  
Suppressor Cell ◽  
Allograft Survival ◽  
Myeloid Derived Suppressor Cell

scholarly journals Early postnatal overnutrition accelerates aging-associated epigenetic drift in pancreatic islets

2019 ◽  
Vol 5 (3) ◽  
Author(s):  
Ge Li ◽  
Tihomira D Petkova ◽  
Eleonora Laritsky ◽  
Noah Kessler ◽  
Maria S Baker ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Dna Methylation ◽  
Pancreatic Islets ◽  
Cell Function ◽  
Control Male ◽  
Small Litter ◽  
Endoplasmic Reticulum Calcium ◽  
Expression Of Genes ◽  
Β Cell Function

Abstract Pancreatic islets of type 2 diabetes patients have altered DNA methylation, contributing to islet dysfunction and the onset of type 2 diabetes. The cause of these epigenetic alterations is largely unknown. We set out to test whether (i) islet DNA methylation would change with aging and (ii) early postnatal overnutrition would persistently alter DNA methylation. We performed genome-scale DNA methylation profiling in islets from postnatally over-nourished (suckled in a small litter) and control male mice at both postnatal day 21 and postnatal day 180. DNA methylation differences were validated using quantitative bisulfite pyrosequencing, and associations with expression were assessed by RT-PCR. We discovered that genomic regions that are hypermethylated in exocrine relative to endocrine pancreas tend to gain methylation in islets during aging (R2 = 0.33, P < 0.0001). These methylation differences were inversely correlated with mRNA expression of genes relevant to β cell function [including Rab3b (Ras-related protein Rab-3B), Cacnb3 (voltage-dependent L-type calcium channel subunit 3), Atp2a3 (sarcoplasmic/endoplasmic reticulum calcium ATPase 3) and Ins2 (insulin 2)]. Relative to control, small litter islets showed DNA methylation differences directly after weaning and in adulthood, but few of these were present at both ages. Surprisingly, we found substantial overlap of methylated loci caused by aging and small litter feeding, suggesting that the age-associated gain of DNA methylation happened much earlier in small litter islets than control islets. Our results provide the novel insights that aging-associated DNA methylation increases reflect an epigenetic drift toward the exocrine pancreas epigenome, and that early postnatal overnutrition may accelerate this process.

scholarly journals Altered proinsulin conversion in rat pancreatic islets exposed long-term to various glucose concentrations or interleukin-1β

2007 ◽  
Vol 192 (2) ◽  
pp. 381-387 ◽  
Author(s):  
Andreas Börjesson ◽  
Carina Carlsson
Keyword(s):  
Pancreatic Islets ◽  
Cell Function ◽  
Culture Media ◽  
Mrna Level ◽  
Interleukin 1Β ◽  
Mrna Levels ◽  
Rat Pancreatic Islets ◽  
Significant Prolongation ◽  
Β Cell Function

In order to elucidate a possible relationship between β-cell function and conversion of proinsulin to insulin, isolated rat pancreatic islets were maintained in tissue culture for 1 week at various glucose concentrations (5.6–56 mM). Studies were also conducted on islets cultured for 48 h with interleukin-1β (IL-1β). By pulse-chase labelling and immunoprecipitation, the relative contents of newly synthesized proinsulin and insulin were determined. ELISA was used to analyse insulin and proinsulin content in medium and within islets. Using real-time PCR, the mRNA levels of proinsulin converting enzymes (PC1 and PC2) were studied. Islets cultured at 56 mM glucose had an increased proportion of newly synthesized proinsulin when compared with islets cultured at 5.6 mM glucose after a 90-min chase periods, however, no difference was observed after culture at 11 and 28 mM glucose. ELISA measurements revealed that culture at increased glucose concentrations as well as islet exposure to IL-1β increased proinsulin accumulation in the culture media. The mRNA expression of PC1 was increased after culture at 11 and 28 mM glucose. Treatment for 48 h with IL-1β increased the proportion of proinsulin both at 45 and 90 min when compared with control islets. These islets also displayed a decreased mRNA level of PC1 as well as PC2. Calculations of the half-time for proinsulin demonstrated a significant prolongation after treatment with IL-1β. We conclude that a sustained functional stimulation by glucose of islets is coupled to a decreased conversion of proinsulin which is also true for islets treated with IL-1β. This may contribute to the elevated levels of proinsulin found both at the onset of type 1 diabetes as well as in type 2 diabetes.

CORRELATION BETWEEN HIGH-MOLECULAR-WEIGHT Fcγ-RECEPTOR-BLOCKING FACTORS IN SERUM AND RENAL ALLOGRAFT SURVIVAL

1987 ◽  
Vol 44 (2) ◽  
pp. 227-233 ◽  
Author(s):  
Margaret A. Forwell ◽  
Jane E. Cocker ◽  
Moira G. Peel ◽  
D. J. Tsakiris ◽  
J. D. Briggs ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Renal Allograft ◽  
Allograft Survival ◽  
Fcγ Receptor ◽  
Receptor Blocking ◽  
Blocking Factors
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