Obstacles in the Application of Microencapsulation in Islet Transplantation

1993 ◽  
Vol 16 (4) ◽  
pp. 205-212 ◽  
Author(s):  
P. De Vos ◽  
G.H.J. Wolters ◽  
W.M. Fritschy ◽  
R. Van Schilfgaarde
Keyword(s):  
Islet Transplantation ◽  
Insulin Response ◽  
Limiting Factors ◽  
Survival Times ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Functional Aspects ◽  
Second Category ◽  
Transplantation Site ◽  
Insight Into

Several factors stand in the way of successful clinical transplantation of alginate-polylysine-alginate microencapsulated pancreatic islets. These obstacles can be classified into three categories. The first regards the technical aspects of the production process. Limiting factors are the insufficient ability to produce small capsules with an adequate production rate, and insufficient insight into the factors determining the optimal chemical and mechanical properties of the capsules. The second category regards the functional aspects of the microencapsulated islets, such as the limitations of the transplantation site and the absence of a physiologic insulin response of the encapsulated islets to elevated blood glucose levels. The third category regards the fact that survival times of encapsulated islet grafts are still limited to several weeks or months, which is mainly explained by a pericapsular fibrotic overgrowth reaction as a consequence of the bioincom-patibility of the capsule membrane. This study describes these obstacles, and thereby summarizes the requirements needed for successful clinical application of encapsulated islet transplantation.

scholarly journals A New Islet Transplantation Method Combining Mesenchymal Stem Cells with Recombinant Peptide Pieces, Microencapsulated Islets, and Mesh Bags

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 299
Author(s):  
Ryo Kogawa ◽  
Kentaro Nakamura ◽  
Yusuke Mochizuki
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Blood Glucose ◽  
Islet Transplantation ◽  
The Other ◽  
Recombinant Peptide ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Transplantation Site ◽  
Mesh Bag

Microencapsulated islet transplantation was widely studied as a promising treatment for type 1 diabetes mellitus. However, micro-encapsulated islet transplantation has the following problems—early dysfunction of the islets due to the inflammatory reaction at the transplantation site, and hyponutrition and hypoxia due to a lack of blood vessels around the transplantation site, and difficulty in removal of the islets. On the other hand, we proposed a cell transplantation technique called CellSaic, which was reported to enhance the vascular induction effect of mesenchymal stem cells (MSCs) in CellSaic form, and to enhance the effect of islet transplantation through co-transplantation. Therefore, we performed islet transplantation in diabetic mice by combining three components—microencapsulated islets, MSC-CellSaic, and a mesh bag that encapsulates them and enables their removal. Mesh pockets were implanted in the peritoneal cavity of Balb/c mice as implantation sites. After 4 weeks of implantation, a pocket was opened and transplanted with (1) pancreatic islets, (2) microencapsulated islets, and (3) microencapsulated islets + MSC-CellSaic. Four weeks of observation of blood glucose levels showed that the MSC-CellSaic co-transplant group showed a marked decrease in blood glucose levels, compared to the other groups. A three-component configuration of microcapsules, MSC-CellSaic, and mesh bag was shown to enhance the efficacy of islet transplantation.

scholarly journals Possibility of adiponectin use to improve islet transplantation outcomes

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Naoaki Sakata ◽  
Gumpei Yoshimatsu ◽  
Kiyoshi Chinen ◽  
Ryo Kawakami ◽  
Shohta Kodama
Keyword(s):  
Islet Transplantation ◽  
Therapeutic Effect ◽  
Tolerance Test ◽  
Clinical Settings ◽  
Vascular Endothelial ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Severe Diabetes ◽  
Endothelial Growth Factor

AbstractAlthough islet transplantation (ITx) is a promising therapy for severe diabetes mellitus, further advancements are necessary. Adiponectin, an adipokine that regulates lipid and glucose metabolism, exerts favorable effects on islets, such as reinforcement of the insulin-releasing function. This study evaluated the possibility of adiponectin use to improve ITx outcomes. We treated mouse islets with 10 µg/mL recombinant mouse adiponectin by overnight culture and then assessed the insulin-releasing, angiogenic, and adhesion functions of the islets. Furthermore, 80 syngeneic islet equivalents with or without adiponectin treatment were transplanted into the renal subcapsular space of diabetic mice. In in vitro assessment, released insulin at high glucose stimulation, insulin content, and expressions of vascular endothelial growth factor and integrin β1 were improved in adiponectin-treated islets. Furthermore, adiponectin treatment improved the therapeutic effect of ITx on blood glucose levels and promoted angiogenesis of the transplanted islets. However, the therapeutic effect was not pronounced in glucose tolerance test results. In conclusion, adiponectin treatment had preferable effects in the insulin-releasing, angiogenic, and adhesion functions of islets and contributed to the improvement of ITx. The future use of adiponectin treatment in clinical settings to improve ITx outcomes should be investigated.

Combined effect of 2-deoxy-D-glucose and exercise on plasma catecholamine response

1992 ◽  
Vol 72 (1) ◽  
pp. 361-365 ◽  
Author(s):  
F. Trabelsi ◽  
S. Cardin ◽  
R. Helie ◽  
G. R. Brisson ◽  
J. M. Lavoie
Keyword(s):  
Blood Glucose ◽  
Glucose Utilization ◽  
Saline Solution ◽  
Competitive Inhibition ◽  
Plasma Catecholamine ◽  
Control Groups ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Catecholamine Response ◽  
Insight Into

2-Deoxy-D-glucose (2-DG) is a nonmetabolizable analogue of glucose that, by competitive inhibition of glucose utilization, produces a central neuroglucopenia and a peripheral hyperglycemia. This glucopenic agent was used to gain more insight into the combined effects of central glucopenia and exercise on plasma catecholamine response. This was carried out by comparing one group of exercising (26 m/min, 0% grade) rats injected with 2-DG (2-DG-EX; 250 mg/kg iv) with two control groups: one group of exercising rats injected with a saline solution (SAL-EX) and one group of resting rats injected with 2-DG (2-DG-RE). Significant (P less than 0.05) increases in blood glucose levels were observed 10 min after administration of 2-DG (7.2–13.8 and 7.3–12.4 mmol/l in 2-DG-EX and 2-DG-RE groups, respectively). These elevated blood glucose levels were maintained throughout the experiment in the 2-DG-RE condition but decreased in 2-DG-EX rats to levels observed in the SAL-EX group after 45 min of running (13.8–8.0 mmol/l). The combination of 2-DG-induced neuroglucopenia and exercise resulted in an additive response of norepinephrine (0.59 vs. 0.34 and 0.34 ng/ml; t = 12 min) and an amplified epinephrine response (1.4 vs. 0.37 and 0.31 ng/ml; t = 12 min) compared with the responses to each stimulus alone (2-DG-EX vs. 2-DG-RE and SAL-EX, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Increased Slc12a1 expression in β-cells and improved glucose disposal in Slc12a2 heterozygous mice

2015 ◽  
Vol 227 (3) ◽  
pp. 153-165 ◽  
Author(s):  
Saeed Alshahrani ◽  
Mohammed Mashari Almutairi ◽  
Shams Kursan ◽  
Eduardo Dias-Junior ◽  
Mohamed Mahmoud Almiahuob ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Response ◽  
Chloride Concentration ◽  
Glucose Disposal ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Glucose Levels ◽  
Fasting Glycemia ◽  
Blood Glucose Levels ◽  
Glucose Stimulated Insulin Secretion

The products of theSlc12a1andSlc12a2genes, commonly known as Na+-dependent K+2Cl−co-transporters NKCC2 and NKCC1, respectively, are the targets for the diuretic bumetanide. NKCCs are implicated in the regulation of intracellular chloride concentration ([Cl−]i) in pancreatic β-cells, and as such, they may play a role in glucose-stimulated plasma membrane depolarization and insulin secretion. Unexpectedly, permanent elimination of NKCC1 does not preclude insulin secretion, an event potentially linked to the homeostatic regulation of additional Cl−transporters expressed in β-cells. In this report we provide evidence for such a mechanism. Mice lacking a single allele ofSlc12a2exhibit lower fasting glycemia, increased acute insulin response (AIR) and lower blood glucose levels 15–30 min after a glucose load when compared to mice harboring both alleles of the gene. Furthermore, heterozygous expression or complete absence ofSlc12a2associates with increased NKCC2 protein expression in rodent pancreatic β-cells. This has been confirmed by using chronic pharmacological down-regulation of NKCC1 with bumetanide in the mouse MIN6 β-cell line or permanent molecular silencing of NKCC1 in COS7 cells, which results in increased NKCC2 expression. Furthermore, MIN6 cells chronically pretreated with bumetanide exhibit increased initial rates of Cl−uptake while preserving glucose-stimulated insulin secretion. Together, our results suggest that NKCCs are involved in insulin secretion and that a singleSlc12a2allele may protect β-cells from failure due to increased homeostatic expression ofSlc12a1.

scholarly journals Suitability of denervated muscle flaps as recipient sites for pancreatic islet cell transplantation

2021 ◽  
Vol 48 (1) ◽  
pp. 133-143
Author(s):  
Jong-Lim Park ◽  
Taewoon Kim ◽  
Baek-Kyu Kim
Keyword(s):  
Blood Glucose ◽  
Islet Transplantation ◽  
Islet Cell ◽  
Gastrocnemius Muscle ◽  
Muscle Flap ◽  
Islet Cell Transplantation ◽  
Muscle Flaps ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Polymerase Chain

Background Extensive research has been conducted on islet transplantation as a possible cure for diabetes. Islet transplantation in the liver via the portal vein has shown remarkable results, but numerous other recipient sites are currently being investigated. We aimed to show the effectiveness of using a muscle flap as a recipient site for islet transplantation.Methods Islet cells were harvested from 12 isogenic Lewis rats, and then diabetes was induced in another 12 isogenic Lewis rats by streptozotocin injection. In six rats, 3,000 islets were transplanted into gastrocnemius muscle flaps, and in the other six rats, the same number of islets were transplanted into the gastrocnemius muscle. The transplanted islet cell function between the two groups was compared by means of blood glucose tests, glucose tolerance tests, immunohistochemistry, and real-time reverse transcription polymerase chain reaction.Results In the muscle flap group, blood glucose levels significantly decreased after islet transplantation. Blood glucose levels were significantly different between the two groups at 3 weeks after transplantation. The muscle flap group showed nearly normoglycemic results upon the glucose tolerance test, whereas the muscle group was hyperglycemic. Immunohistochemical evaluation showed positive results against insulin and glucagon in biopsies of both groups, and the islet cell density was higher in the muscle flap group. There were no statistically significant differences between the two groups in real-time reverse transcription polymerase chain reaction results.Conclusions Our results suggest that muscle flaps are promising candidates for islet cell transplantation.

scholarly journals The acute effect of baobab fruit on cognitive performance, cerebral blood flow and blood glucose levels.

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Sarah Docherty ◽  
Crystal Haskell-Ramsay
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Blood Glucose ◽  
Phenolic Compounds ◽  
Vitamin C ◽  
Cognitive Performance ◽  
Insulin Response ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Fruit Powder

AbstractBaobab fruit contains high levels of phenolic compounds and vitamin C. Previous work has associated these phenolic compounds and vitamin C with a range of health benefits including improvements in cerebral blood flow and cognition. In vivo, it has been demonstrated that consumption of baobab fruit can reduce the glycaemic response, which may provide a mechanism for cognitive benefits as other research has shown that variations in blood glucose levels can modulate cognitive performance. Preliminary work found that consumption of 15 g baobab fruit extract significantly improved reaction time but increased number of errors on an executive function task. Taken together it would suggest baobab fruit has the potential to improve cognitive performance that could be attributed to changes in cerebral blood flow and blood glucose levels.The current study aimed to determine the effect of baobab fruit on cognitive performance, cerebral blood flow and blood glucose levels in a healthy young sample.This randomised, placebo-controlled, double-blind, counterbalanced-crossover study assessed the effect of 10 g baobab fruit powder or sugar matched control in 24 healthy participants (17 female, 7 male, mean age = 22.91 SD = 3.37). All participants completed the cognitive assessments, a subset of 14 completed the cerebral blood flow and blood glucose assessments (mean age = 23.21, SD = 2.46). Participants completed baseline tasks before consuming a drink containing either 10 g baobab fruit powder or placebo, there was then a 45-minute absorption period before participants completed cognitive tasks again. Seven days after participants returned and completed the same procedure but consumed the opposite drink. In the 14 participant subset, cerebral blood flow was measured throughout using Near Infrared Spectroscopy (NIRS) and blood glucose was measured before testing, after absorption period and upon completion of post doseUsing the MIXED procedure in SPSS, results showed that after consumption of baobab there was improved accuracy on a sustained attention task and fewer errors on the last repetition of a serial subtraction task. Baobab consumption led to increased blood glucose levels but there was no significant effect on cerebral blood flow.Results show that, in this sample, 10 g baobab fruit can improve certain aspects of cognitive performance and increase circulating blood glucose levels, which may explain these improvements. However, there was no significant effect on any cerebral blood flow measures. Future work may wish to explore further glucoregulation activity (in particular insulin response) after baobab consumption as a potential underlying mechanism.

scholarly journals Comparison of the Effects of Liraglutide on Islet Graft Survival Between Local and Systemic Delivery

2020 ◽  
Vol 29 ◽  
pp. 096368972097124
Author(s):  
Song Mi Lee ◽  
Donghee Kim ◽  
Kyung Min Kwak ◽  
Phyu Phyu Khin ◽  
Oh Kyung Lim ◽  
...  
Keyword(s):  
Islet Transplantation ◽  
Diabetic Mouse ◽  
Diabetic Mice ◽  
Systemic Delivery ◽  
Systemic Injection ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Promising Treatment ◽  
Glucagon Like Peptide 1 ◽  
Islet Survival

Islet transplantation has emerged as a promising treatment for type 1 diabetes mellitus. Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, protects beta cells after islet transplantation by improving glycemic control through several mechanisms. In this study, we compared the effects of local pretreatment and systemic treatment with liraglutide on islet transplantation in a diabetic mouse model. Streptozotocin (STZ)-induced diabetic C57BL/6 mice were transplanted with syngeneic islets under the kidney capsule. Isolated islets were either locally treated with liraglutide before transplantation or mice were treated systemically by intraperitoneal injection after islet transplantation. Local pretreatment of islets with liraglutide was more effective in increasing body weight, decreasing hemoglobin A1c levels, and lowering blood glucose levels in STZ-diabetic mice transplanted with islets. Local pretreatment was also more effective in increasing insulin secretion and islet survival in STZ-diabetic mice. Histological analysis of the transplantation site revealed fewer apoptotic cells following local pretreatment compared with systemic injection of liraglutide. These findings indicate that liraglutide administered once locally before transplantation might have superior effects on islet preservation than systemic administration.

The Possibility of Adiponectin in Islet Transplantation

2021 ◽  
Author(s):  
Naoaki Sakata ◽  
Gumpei Yoshimatsu ◽  
Kiyoshi Chinen ◽  
Ryo Kawakami ◽  
Shohta Kodama
Keyword(s):  
Blood Glucose ◽  
Islet Transplantation ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Vascular Endothelial ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Severe Diabetes ◽  
Endothelial Growth Factor

Abstract Islet transplantation (ITx), a promising therapy for severe diabetes mellitus, needs further evolution. Adiponectin, an adipokine that regulates lipid and glucose metabolism, has some benefits that may improve (e.g., reinforcement of insulin-releasing function). This study attempted to evaluate the possibility of adiponectin for ITx improvement. Mouse islets were treated with 10 µg/mL recombinant mouse adiponectin by overnight culture (defined as adiponectin (+)). The islets’ insulin-releasing, angiogenic, and adhesion functions were assessed and compared with islets without adiponectin treatment (adiponectin (−)). Furthermore, 80 syngeneic islets, with or without adiponectin treatment, were transplanted into the renal subcapsular space of diabetic mice. In vitro assessment showed improved insulin-releasing, angiogenic, and adhesion functions adiponectin (+). Moreover, released insulin volume at high glucose stimulation, insulin content, and expressions of vascular endothelial growth factor and integrin β1 were improved in islets with adiponectin treatment. Furthermore, the ITx therapeutic effect with adiponectin treatment was partial. There was a significant improvement in blood glucose levels in adiponectin (+). No significant differences were noted in plasma insulin and area under the curve of blood glucose level in glucose tolerance test. In conclusion, adiponectin has various usefulness for improving ITx outcomes. Thus, further studies are necessary for this possibility.

Anaesthesia and changes in parameters that reflect glucose metabolism in pigs – a pilot study

2016 ◽  
Vol 51 (5) ◽  
pp. 509-517 ◽  
Author(s):  
Elin Manell ◽  
Marianne Jensen-Waern ◽  
Patricia Hedenqvist
Keyword(s):  
Blood Glucose ◽  
Pilot Study ◽  
Insulin Response ◽  
Growing Pigs ◽  
Laboratory Animals ◽  
Oral Glucose ◽  
Diabetes Research ◽  
Imaging Procedures ◽  
Glucose Levels ◽  
Blood Glucose Levels

Pigs are commonly used in diabetes research due to their many physiological similarities to humans. They are especially useful in imaging procedures because of their large size. However, to achieve imaging procedures the pig must lie completely still, and thus needs to be anaesthetized. Most anaesthetic drugs used in laboratory animals affect carbohydrate metabolism by the inhibition of insulin release. The aim of this pilot study was primarily to develop an anaesthetic protocol for pigs that did not have an effect on blood glucose levels throughout the 3 h of anaesthesia; and secondly, to evaluate the most promising protocol in combination with an oral glucose tolerance test (OGTT). Two anaesthetic protocols were used in four growing pigs. Intravenous propofol infusion caused hyperglycaemia in three out of four pigs within 5–10 min after induction and was therefore excluded. Intravenous infusion with tiletamine, zolazepam and butorphanol (TZB) for 3 h did not affect blood glucose levels. The pigs underwent OGTT twice, once without anaesthesia and once with TZB induction after glucose intake. Anaesthesia during OGTT resulted in a lower area under the curve (AUC) of glucose ( P < 0.05), higher AUC of glucagon ( P < 0.05) and an insulin response less than 10% of that during OGTT without anaesthesia. In conclusion, long-term infusion anaesthesia with TZB does not affect glucose homeostasis in pigs. However, the protocol is not effective when combined with OGTT, as glucose, insulin and glucagon levels are affected.

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