Insulin independence after living-donor distal pancreatectomy and islet allotransplantation

Matsumoto, Shinichi; Okitsu, Teru; Iwanaga, Yasuhiro; Noguchi, Hirofumi; Nagata, Hideo; Yonekawa, Yukihide; Yamada, Yoshio; Fukuda, Kazuhito; Tsukiyama, Katsushi; Suzuki, Haruhiko; Kawasaki, Yukiko; Shimodaira, Makiko; Matsuoka, Kiwamu; Shibata, Toshiya; Kasai, Yasunari; Maekawa, Taira; Shapiro, AM James; Tanaka, Kōichi

doi:10.1016/s0140-6736(05)66383-0

Cited by 208 publications

(142 citation statements)

References 9 publications

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“…While the aetiology of fulminant type 1 diabetes is not clear, substantial regeneration of pancreatic beta cells was found to be impossible in this subtype, as well as in conventional type 1A diabetes [19]. Early progression of diabetic complications and long-standing unstable blood glucose control might necessitate a more aggressive intervention, such as islet-transplantation from living donors [25], in fulminant type 1 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Fulminant type 1 diabetes as a high risk group for diabetic microangiopathy—a nationwide 5-year-study in Japan

et al. 2007

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Aims/hypothesis The aim of the present study was to assess the development of microangiopathy in patients with fulminant type 1 diabetes, a novel subtype of type 1B diabetes. Materials and methods In a nationwide survey, we followed 41 patients with fulminant type 1 diabetes and 76 age-and sex-matched patients with type 1A diabetes for 5 years. The following data were recorded every 12 months after the onset of diabetes: seven-point blood glucose concentrations, HbA 1c level, urinary albumin excretion, serum C-peptide level, blood pressure, daily dosages of insulin, frequency of severe hypoglycaemic episodes, and neurological and fundoscopic examination. ResultsThe 5-year cumulative incidence of microangiopathy was 24.4% in fulminant type 1 diabetes and 2.6% in type 1A diabetes. In longitudinal studies using the KaplanMeier method, the cumulative incidence of each form of microangiopathy was significantly higher in fulminant type 1 diabetes than in type 1A diabetes; retinopathy was 9.8% vs 0% (p=0.014), nephropathy 12.2% vs 2.6% (p=0.015) and neuropathy 12.2% vs 1.3% (p=0.010), respectively. Mean HbA 1c levels were similar in the fulminant and type 1A diabetes groups during the follow-up periods. However, the mean M-value, mean insulin dosages and the frequency of severe hypoglycaemic episodes were significantly higher, and the mean postprandial C-peptide level was significantly lower in the fulminant type 1 diabetes group.

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Section: Discussionmentioning

confidence: 99%

Fulminant type 1 diabetes as a high risk group for diabetic microangiopathy—a nationwide 5-year-study in Japan

et al. 2007

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“…Endogenous secretion of insulin to near physiological levels can be restored by intraportal infusion of pancreatic islets derived from brain-dead or, as recently described, living donors [2]. Unfortunately, the variability of human islet isolation outcome remains an exasperating and expensive issue in clinical islet transplantation [1].…”

Section: Introductionmentioning

confidence: 99%

Acute insulin response of donors is correlated with pancreatic islet isolation outcome in the pig

et al. 2005

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Aims/hypothesis: Unpredictability of islet isolation outcome remains a frustrating and costly issue in the clinical implementation of islet transplantation. The aim of this experimental study was to test the hypothesis that the donor's insulin secretory reserve, an in vivo surrogate of functional pancreatic mass, is correlated with the outcome of islet isolation. Methods: Insulin secretory reserve was evaluated in 28 healthy adult minipigs prior to pancreatectomy and islet isolation. Blood glucose and insulinaemia were measured before and 1, 3, 5, 10, 15, 30, 60 and 90 min after glucose infusion. Following total pancreatectomy, islet isolation was performed according to Ricordi's semi-automated method, and the total number of islets obtained was determined. Fasting blood glucose, insulinaemia, acute insulin response (AIR), maximal insulinaemia and the glucose decay constant (K G ) were calculated, and possible associations with the outcome of islet isolation were assessed. Results: AIR and maximal insulinaemia after glucose injection were correlated with the outcome of islet isolation (p<0.01). Mean values for AIR and maximal insulinaemia were significantly different between animals in which islet isolation was successful (n=11) vs those in which it was unsuccessful (n=17) (77.6±13.7 μU/ml vs 42.3±7.8 μU/ml, p<0.05; 144.7± 21.6 μU/ml vs 71.9±10.4 μU/ml, p<0.05, respectively). Conclusions/interpretation: This study suggests that the donor's pancreatic endocrine mass, as estimated by AIR, is a major determinant of the outcome of islet isolation in large mammals. Our results may explain the frustrating variability of human islet isolation outcome and could lead to a new approach for optimising the selection of brain-dead and/or living pancreas donors.

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“…Application of the Edmonton protocol has markedly improved the outcome for pancreatic islet transplantation as a therapeutic strategy for type 1 diabetes [1][2][3]. However, the insulin independence rate after islet transplantation from one donor pancreas remains low.…”

Section: Introductionmentioning

confidence: 99%

Activation of c-Jun NH2-terminal kinase (JNK) pathway during islet transplantation and prevention of islet graft loss by intraportal injection of JNK inhibitor

Noguchi

Nakai

Ueda³

et al. 2007

Diabetologia

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Aims/hypothesis Although application of the Edmonton protocol has markedly improved the outcome for pancreatic islet transplantation, the insulin independence rate after islet transplantation from one donor pancreas has remained low. During the isolation process and subsequent clinical transplantation, islets are subjected to severe adverse conditions that impair survival and ultimately contribute to graft failure. The aim of this study was to map the c-Jun NH 2 -terminal kinase (JNK) pathway that mediates islet loss during islet transplantation and to clarify whether intraportal injection with JNK inhibitor during islet transplantation can prevent islet graft loss. Methods We measured JNK activity in the liver, fat and muscle of diabetic mice and in the liver immediately after islet transplantation. We examined the effect of intraportal injection of JNK inhibitory peptide at islet transplantation. Results JNK activity became progressively higher at least until 24 h after transplantation. The cell-permeable peptide of JNK inhibitor was delivered not only in the liver but also in other insulin target organs, preventing JNK activation in the liver at least until 24 h after transplantation and reducing JNK activity in these insulin target organs. Moreover, the peptide inhibitor prevented islet graft loss immediately after transplantation and improved islet transplant outcome. Conclusions/interpretation These findings suggest that control of the JNK pathway is extremely important in islet transplantation and that intraportal injection of JNK inhibitor during islet transplantation (addition of JNK inhibitor to transplant media) could prevent the impairment of islet cells, leading to improved outcome for pancreatic islet transplantation.

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Insulin independence after living-donor distal pancreatectomy and islet allotransplantation

Cited by 208 publications

References 9 publications

Fulminant type 1 diabetes as a high risk group for diabetic microangiopathy—a nationwide 5-year-study in Japan

Fulminant type 1 diabetes as a high risk group for diabetic microangiopathy—a nationwide 5-year-study in Japan

Acute insulin response of donors is correlated with pancreatic islet isolation outcome in the pig

Activation of c-Jun NH2-terminal kinase (JNK) pathway during islet transplantation and prevention of islet graft loss by intraportal injection of JNK inhibitor

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