Progressive Deterioration of Endocrine Function After Intraportal but Not Kidney Subcapsular Rat Islet Transplantation

Hiller, Wolfgang; Klempnauer, Jürgen; Lück, R.; Steiniger, Birte

doi:10.2337/diab.40.1.134

Cited by 53 publications

(25 citation statements)

References 16 publications

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“…It could be hypothesized that grafted LP-islets would not decrease the high glycemia of diabetic recipient rats while NP ones would be more effective; however, this was not observed. It has been shown that a simple islet transplantation of a short duration, up to 5 days, and independent of islet number did not correct the hyperglycemia of STZ diabetic rats; however, long-term islet grafts promote fed-state normoglycemia depending on the site of the transplantations [31]–[33].…”

Section: Discussionmentioning

confidence: 99%

Maternal Protein Malnutrition Does Not Impair Insulin Secretion from Pancreatic Islets of Offspring after Transplantation into Diabetic Rats

et al. 2012

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Pancreatic islets from adult rats whose mothers were protein restricted during lactation undersecrete insulin. The current work analyzes whether this secretory dysfunction can be improved when the pancreatic islets are grafted into hyperglycemic diabetic rats. Two groups of rats were used: the adult offspring from dams that received a low protein diet (4%) during the initial 2/3 of lactation (LP) and, as a control, the adult offspring from dams that consumed a normal protein diet (23%) during the entire period of lactation (NP). Islets from NP- and LP-rats were transplanted into diabetic recipient rats, which were generated by streptozotocin treatment. The islets were transplanted via the portal vein under anesthesia. The fed blood glucose levels were monitored during the 4 days post-transplantation. Transplanted islets from LP-rats (T LP) decreased the fed glucose levels of diabetic rats 34% (21.37±0.24 mM, p<0.05); however, the levels still remained 2-fold higher than those of the sham-operated controls (6.88±0.39 mM, p<0.05). Grafts with NP-islets (T NP) produced the same effect as the LP-islets in diabetic rats. The high fasting blood glucose levels of diabetic rats were improved by the transplantations. Islet grafts from both rat groups recovered 50% of the retroperitoneal fat mass of the diabetic rats (0.55±0.08 g/100 g of body weight for T NP and 0.56±0.07 g/100 g of body weight for T LP, p<0.05). Because pancreatic islets from both the NP- and LP-rats were able to regulate fasting blood glucose concentrations in hyperglycemic rats, we propose that the altered function of pancreatic islets from LP-rats is not permanent.

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Section: Discussionmentioning

confidence: 99%

Maternal Protein Malnutrition Does Not Impair Insulin Secretion from Pancreatic Islets of Offspring after Transplantation into Diabetic Rats

et al. 2012

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“…Intrahepatically transplanted islets may also be lost as a result of localised, insulin-induced hepatic steatosis, lipotoxicity and inflammation [15]. These influences can damage the islets, and long-term studies have identified the non-immune-mediated loss of function from intrahepatically transplanted islets [16]. Research continues to increase the success rate of portal delivery; however, the local milieu of intrahepatically delivered islets cannot be readily manipulated and provides a significant challenge to substantive improvements.…”

Section: Introductionmentioning

confidence: 99%

Advancing islet transplantation: from engraftment to the immune response

Gibly¹,

Graham²,

Luo³

et al. 2011

Diabetologia

127

108

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The promise and progress of islet transplantation for treating type 1 diabetes has been challenged by obstacles to patient accessibility and long-term graft function that may be overcome by integrating emerging technologies in biomaterials, drug delivery and immunomodulation. The hepatic microenvironment and traditional systemic immunosuppression stress the vulnerable islets and contribute to the limited success of transplantation. Locally delivering extracellular matrix proteins and trophic factors can enhance transplantation at extrahepatic sites by promoting islet engraftment, revascularisation and long-term function while avoiding unintended systemic effects. Cell- and cytokine-based therapies for immune cell recruitment and reprogramming can inhibit local and systemic immune system activation that normally attacks transplanted islets. Combined with antigen-specific immunotherapies, states of operational tolerance may be achievable, reducing or eliminating the long-term pharmaceutical burden. Integration of these technologies to enhance engraftment and combat rejection may help to advance the therapeutic efficacy and availability of islet transplantation.

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“…Numerous sites have been investigated as an ideal islet implantation site, including the kidney subcapsule (6, 7), liver (6-8), peritoneum (8, 9) omental pouch (10), skeletal muscle (9, 11), subcutaneous tissue (8, 11), and spleen (6). However, it is difficult to determine the ideal implantation site based on these published data because of the variety of donor islets (fetal islet-like clusters vs. adult islets), the species of donor and recipients (rat, mouse, and pig), the parameters used to determine the success of implantation (metabolic control, oxygen tension, or functional mass) and the number of sites compared.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Four Pancreatic Islet Implantation Sites

Kim

Park

et al. 2010

J Korean Med Sci

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Although the liver is the most common site for pancreatic islet transplantation, it is not optimal. We compared kidney, liver, muscle, and omentum as transplantation sites with regard to operative feasibility, and the efficiency of implantation and glycemic control. Islets from C57BL/6 mice were transplanted into diabetic syngeneic recipients. The mean operative time and mortality were measured to assess feasibility. To assess implantation efficiency, the marginal mass required to cure diabetes and the mean time taken to achieve normoglycemia were measured. A glucose tolerance test was performed to assess glycemic control efficiency. The data are listed in the order of the kidney, liver, muscle, and omentum, respectively. The mean mortality rate was 6.7, 20.0, 7.1, and 12.5%; the mean operative time was 10.2, 27.4, 11.2, and 19.8 min; the marginal islet mass was 100, 600, 600, and 200 islet equivalence units and the mean time to reach euglycemia was 3.0, 15.1, 26.6, and 13.9 days. The glucose kinetics of omental pouch islets was the most similar to controls. Thus, a strategic approach is required for deciding on the best transplantation recipient sites after considering donor sources and islet volume. Alternatives can be chosen based on safety or efficacy.

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Progressive Deterioration of Endocrine Function After Intraportal but Not Kidney Subcapsular Rat Islet Transplantation

Cited by 53 publications

References 16 publications

Maternal Protein Malnutrition Does Not Impair Insulin Secretion from Pancreatic Islets of Offspring after Transplantation into Diabetic Rats

Maternal Protein Malnutrition Does Not Impair Insulin Secretion from Pancreatic Islets of Offspring after Transplantation into Diabetic Rats

Advancing islet transplantation: from engraftment to the immune response

Comparison of Four Pancreatic Islet Implantation Sites

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