Beta cell mass and growth after syngeneic islet cell transplantation in normal and streptozocin diabetic C57BL/6 mice.

Montaña, E; Bonner-Weir, Susan; Weir, Gordon C.

doi:10.1172/jci116297

Cited by 189 publications

(164 citation statements)

References 38 publications

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“…Over time Patient 2 increased basal C-peptide secretion, but presented with a decrease in glucagon-stimulated C-peptide response. Although insulin-independence and normal HbA1c are preserved, this finding is likely conform with an exhaustion of a marginal islet mass, similar to observations in type II diabetes or experimental marginal islet mass models (17). In these two patients, the remnant of the pancreatic head is likely to continue to produce insulin and the impact of islet-autotransplantation to the total endogenous insulin secretion and metabolic control is difficult to evaluate.…”

Section: Discussionsupporting

confidence: 70%

Islet Autotransplantation After Left Pancreatectomy for Non-Enucleable Insulinoma

Oberholzer¹,

Máthé²,

Bucher³

et al. 2003

American Journal of Transplantation

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Insulinoma is a rare, almost always benign endocrine tumor of the pancreas, clinically characterized by hyperinsulinemic, hypoglycemic episodes. Surgical excision is the therapy of choice, which may lead to postpancreatectomy diabetes mellitus in the case of extensive pancreatic resection.We present the cases and the metabolic follow up of two patients, 81 and 73 years old, with insulinoma localized close to the main duct in the pancreatic neck. Both patients underwent an 80% left pancreatectomy, avoiding a pancreatico-enteric anastomosis. In order to prevent postpancreatectomy diabetes, the islets from the tumor-free part of the resected pancreas were isolated and injected via a right colic vein into the portal system. After a follow up of 6 and 3 years respectively, both patients remained insulin-independent without any dietary restrictions. Fasting and glucagon-stimulated C-peptide-levels and glycosylated hemoglobin remained within normal range. There were no signs of recurrent insulinoma. Liver biopsy performed in one patient at 1 year after autotransplantation, showed intact, insulin-producing islets within the portal spaces.In conclusion, autologous islet transplantation can preserve the insulin secretory reserve after extended left pancreatectomy for the treatment of benign tumors in the pancreatic neck.

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Section: Discussionsupporting

confidence: 70%

Islet Autotransplantation After Left Pancreatectomy for Non-Enucleable Insulinoma

Oberholzer¹,

Máthé²,

Bucher³

et al. 2003

American Journal of Transplantation

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“…Islet isolation and culture Islets were isolated by using collagenase digestion followed by separation using a density gradient, as previously described in detail [1]. Briefly, under anaesthesia, a laparatomy was performed and the pancreas exposed.…”

Section: Methodsmentioning

confidence: 99%

“…Transplantation of islets of Langerhans can reverse hyperglycaemia in humans as well as in rodent models of diabetes; however, each recipient usually requires islets from two or three donor pancreases [1,2]. Despite recent improvements in human islet isolation, it is evident that what would seem to be sufficient islet mass usually does not truly normalise glucose levels, as most recipients remain glucose intolerant [3].…”

Section: Introductionmentioning

confidence: 99%

Islet transplantation outcomes in mice are better with fresh islets and exendin-4 treatment

King

Lock

et al. 2005

Diabetologia

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Aims/hypothesis: Although islet transplantation in diabetes holds great promise, two or three donor pancreases are usually required to achieve normoglycaemia in human or rodent recipients. We investigated whether there were differences between fresh and cultured islets in terms of transplantation outcome. We also investigated the effects of normoglycaemia during engraftment and the effects of exendin-4, a glucagon-like peptide-1 receptor agonist, on islet transplantation. Materials and methods: Seventy-five fresh islets were transplanted to the right kidney of diabetic mice and 425 fresh islets were transplanted to the left kidney. The mice were treated with exendin-4 or vehicle for 14 days, after which the large graft was removed by left nephrectomy. In a separate set of experiments, islets cultured in the presence or absence of exendin-4 for 72 h, or fresh islets, were transplanted to diabetic mice. In both sets of experiments, blood glucose levels were monitored. Results: Compared with cultured islets, fresh islets were more effective at reversing hyperglycaemia in mice. The treatment of the recipient mice with exendin-4 did not have beneficial effects on glucose homeostasis. However, when islets are cultured, exendin-4 treatment increases the rate of reversal of hyperglycaemia, but not to the degree of fresh islets. Conclusions/ interpretation: Fresh islets are more effective than cultured islets at reversing hyperglycaemia. Exendin-4 has beneficial effects on islet transplantation.

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“…Pancreata were homogenized using acid-alcohol as previously described 15 and insulin levels measured by radioimmunoassay at Linco Diagnostic Services (St. Louis, MO, U.S.A.).…”

Section: Assessment Of Insulin Contentmentioning

confidence: 99%

Glial Cell Line-Derived Neurotrophic Factor Increases β-Cell Mass and Improves Glucose Tolerance

et al. 2008

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Beta cell mass and growth after syngeneic islet cell transplantation in normal and streptozocin diabetic C57BL/6 mice.

Abstract: In islet transplantation, nonimmunological factors such as limited growth capacity or increased death rate could reduce the beta cell mass in the graft and lead to failure of the transplant.

Cited by 189 publications

References 38 publications

Islet Autotransplantation After Left Pancreatectomy for Non-Enucleable Insulinoma

Islet Autotransplantation After Left Pancreatectomy for Non-Enucleable Insulinoma

Islet transplantation outcomes in mice are better with fresh islets and exendin-4 treatment

Glial Cell Line-Derived Neurotrophic Factor Increases β-Cell Mass and Improves Glucose Tolerance

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