1,720,983 research outputs found
Encapsulated islets for diabetes therapy: history, current progress, and critical issues requiring solution.
No full textInsulin therapy became a reality in 1921 dramatically saving lives of people with diabetes, but not protecting them from long-term complications. Clinically successful free islet implants began in 1989 but require life long immunosuppression. Several encapsulated islet approaches have been ongoing for over 30years without defining a clinically relevant product. Macro-devices encapsulating islet mass in a single device have shown long-term success in large animals but human trials have been limited by critical challenges. Micro-capsules using alginate or similar hydrogels encapsulate individual islets with many hundreds of promising rodent results published, but a low incidence of successful translation to large animal and human results. Reduction of encapsulated islet mass for clinical transplantation is in progress. This review covers the status of both early and current studies including the presentation of corporate efforts involved. It concludes by defining the critical items requiring solution to enable a successful clinical diabetes therapy
Assessment of long-term (1 year) graft survival and metabolic and hormonal changes after intrasplenic canine pancreatic microfragment transplantation
No full textAbstract: Few data have been published so far on the long-term metabolic and endocrine consequences of intrasplenic islet autografts in dogs and the available information mainly deals with glucose response and, more rarely, insulin secretion during intravenous glucose tolerance tests. The effect of islet transplantation on glucagon levels has never been reported. In this study we measured glucose, insulin, total glucagon, and pancreatic glucagon in dogs before and after (up to 1 year) intrasplenic islet autografts. Pancreata were retrieved from 21 adult dogs and the islets were isolated by collagenase digestion. The endocrine tissue was transplanted into the spleen by direct pulp injection. Autografts resulted in normoglycaemia in 19 out of 21 dogs (90 %). Among the successfully transplanted dogs, the percentage of functioning grafts was 71 % at 1 year. The metabolic and hormonal results of the follow-up showed that fasting glucose and insulin concentrations did not differ significantly before and after transplantation. However, glucose tolerance and insulin secretion on intravenous glucose tolerance testing were significantly reduced in transplanted animals. Fasting total and pancreatic glucagon, and their integrated releases during the test did not change significantly after islet transplantation. These results demonstrate that : 1) long-term function of intrasplenic canine islet autografts can be achieved in high percentages ; 2) autotransplanted animals have normal or near normal fasting glucose and insulin levels, but reduced glucose disappearance and insulin secretion on intravenous glucose tolerance tests ; 3) normal glucagon secretion is a feature of successfull islet grafts
Sopravvivenza a lungo termine ed effetti metabolici dell'autotrapianto di isole pancreatiche nel cane: effetto della sede di impianto e della massa di isole trapiantate
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In vitro function and xenotransplantation of long-term (3 weeks) cultured porcine islets of Langerhans
No full text[abstract non disponibile
Effects of cyclosporine on insulin secretion and insulin sensitivity in dogs with intrasplenic islet autotransplants
No full textAbstract: Concern about cyclosporine causing adverse effects on glucose metabolism is based mainly on in vitro studies and in vivo data in rodents. However, data on large mammals and humans are much more controversial. Because the drug is used as therapy accompanying pancreatic or isolated islet transplantations, studies in large animals are needed to assess whether cyclosporine inhibits beta-cell function and causes glucose intolerance. To address these issues, we examined intravenous glucose tolerance, islet beta-cell function, and insulin sensitivity in a group of adult mongrel dogs with intrasplenic islet autografts, with and without cyclosporine treatment. Similar fasting plasma glucose and insulin values were found before and after pancreatectomy and islet transplantation. After intravenous glucose, plasma glucose values decreased more slowly in dogs that had undergone transplantation, but not additional adverse effect as a result of cyclosporine was observed. During euglycemic clamp studies, performed at both physiologic and pharmacologic insulin concentrations, the drug had no effect on the total amount of metabolized glucose, and glucose production was unaffected by cyclosporine treatment. Thus intramuscular cyclosporine therapy does not seem to inhibit insulin secretion from heterotopic islets or to affect peripheral and hepatic insulin sensitivity in dogs with intrasplenic islet autografts
Porcine islet function: effects of arginine, leucine, and butyrate
No full text[abstract non disponibile
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