Pancreas Transplantation for Treatment of Diabetes Mellitus

Sutherland, David E.R.; Gruessner, Rainer W.G.; Gruessner, Angelika C.

doi:10.1007/s002680020342

Cited by 121 publications

(76 citation statements)

References 63 publications

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confidence: 59%

“…comparable to that for whole pancreas transplantation [3], can be obtained. However, whereas one whole pancreas is sufficient to reverse hyperglycaemia [3,4], two or more pancreases are generally needed to achieve this when isolated islets are transplanted. Moreover, there seems to be a steady decline in the function of islet grafts, with very few patients remaining insulinindependent beyond 4 years after transplantation [5].…”

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confidence: 59%

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Improved vascular engraftment and function of autotransplanted pancreatic islets as a result of partial pancreatectomy in the mouse and rat

2007

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Aims/hypothesis The few patients subjected to autotransplantation of pancreatic islets after pancreatectomy usually become normoglycaemic after using islets from the resected organ only, whereas allogeneic recipients usually require at least two grafts to retain normoglycaemia. Previous experimental studies have demonstrated that islets transplanted to non-pancreatectomised recipients acquire a markedly decreased blood vessel density, which leads to a hypoxic microenvironment. The aim of the present study was to test the hypothesis that autotransplanted islets have better vascular engraftment and function as a result of the pancreatic surgery involved. Materials and methods In the present study, athymic mice and inbred rats were subjected to a 60% pancreatectomy and transplanted with human or rat islets, respectively, 4 days later. Control animals underwent sham surgery. Blood flow, oxygen tension, vascular density and endocrine volume in the islet grafts were measured 1 month after transplantation. Separate grafts were used for perfusion experiments and for assessment of beta cell proliferation and endocrine cellular apoptosis at different time periods after transplantation.Results Islet grafts in partially pancreatectomised recipients had an increased blood flow, oxygen tension, blood vessel density and endocrine mass 1 month post-transplantation compared with control animals. They also exhibited increased insulin release in perfusion experiments performed 1 month post-transplantation, and decreased cellular apoptosis early after transplantation. Conclusions/interpretation The present study shows that the pancreatectomy procedure itself has beneficial effects on the engraftment of transplanted human and rat islets. Our results provide an additional explanation, besides diminished immunological responses, of the much better outcome of islet autotransplantations compared with allogeneic transplantations in the clinic.

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confidence: 59%

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confidence: 59%

Improved vascular engraftment and function of autotransplanted pancreatic islets as a result of partial pancreatectomy in the mouse and rat

2007

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“…The indication for PTA was established after assessment of benefits and risks for each patient. In line with recommendations from other studies [18][19][20], in our centre we consider PTA for patients who have two or more overt diabetic complications and/or glucose hyperlability with hypoglycaemic unawareness and impaired quality of life. Contraindications include: age >60 years, active smoking, obesity (BMI >30 kg/m 2 ), left ventricular ejection fraction <40%, active malignancy or infection, and unstable psychological profile.…”

Section: Patients' Clinical Datamentioning

confidence: 79%

Pancreas transplant alone has beneficial effects on retinopathy in type 1 diabetic patients

et al. 2006

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Aims/hypothesis The effects of successful pancreas transplant alone (PTA) on chronic complications of diabetes, in particular diabetic retinopathy, remain disputed. We prospectively studied the course of diabetic retinopathy in PTA recipients and in non-transplanted (non-PTA) type 1 diabetic patients. Methods The PTA and non-PTA groups consisted respectively of 33 (follow-up: 30±11 months) and 35 patients (follow-up: 28±10 months). Best corrected visual acuity, slit lamp examination, intraocular pressure measurement, ophthalmoscopy, retinal photographs, and in selected cases angiography were performed. Diabetic retinopathy and its improvement/deterioration were assessed according to criteria proposed by the Eurodiab Study. Results At baseline, 9% of PTA and 6% of non-PTA patients had no diabetic retinopathy, 24 and 29% had non-proliferative diabetic retinopathy (NPDR), whereas 67 and 66% had laser-treated and/or proliferative diabetic retinopathy (LT/ PDR), respectively. No new case of diabetic retinopathy occurred in either group during follow-up. In the NPDR PTA group, 50% of patients improved by one grading, and 50% showed no change. In the LT/PDR PTA, stabilisation was observed in 86% of cases, whereas worsening of retinopathy occurred in 14% of patients. In the NPDR non-PTA group, diabetic retinopathy improved in 20% of patients, remained unchanged in 10%, and worsened in the remaining 70%. In the LT/PDR non-PTA group, retinopathy did not change in 43% and deteriorated in 57% of patients. Overall, the percentage of patients with improved or stabilised diabetic retinopathy was significantly higher in the PTA group. No differences were found between the two groups with regard to cataract lesions and intraocular pressure values. Conclusions/interpretation Despite a relatively short follow-up, our study shows that successful PTA can positively affect the course of diabetic retinopathy.

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“…To date, the only means of achieving such stringent control has been the restoration of beta cell mass through pancreas or islet transplantation, which results in near-perfect control of blood glucose levels without hypoglycaemic episodes that are associated with intensive insulin therapy [7,8]. Pancreas transplantation is currently far more successful in maintaining long-term reversal of hyperglycaemia than islet transplantation, which is still an emerging technology [9][10][11]. However, both approaches are limited by the shortage of available organs and the need for chronic immunosuppression.…”

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confidence: 99%

Evidence for the homeostatic regulation of induced beta cell mass expansion

et al. 2006

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Aims/hypothesis Diabetes results from an insufficient insulin-secreting beta cell mass. Restoration of beta cell mass through pharmaceutically induced endogenous beta cell mass expansion may revolutionise diabetes therapy. However, it remains to be determined whether the induced beta cell mass expansion is under homeostatic regulation. Methods Beta cell mass expansion rates were derived from three separate studies of continuous stimulation of islet neogenesis, including the partial duct obstruction of euglycaemic Syrian hamsters, administration of a pentadecapeptide with the same amino acid sequence as residues 104-118 of islet neogenesis-associated protein ) to euglycaemic Syrian hamsters, as well as to euglycaemic CD-1 mice. The incidence of islet neogenesis, average beta cell size, and beta cell replication and apoptotic rates were determined. Results Partial duct obstruction led to a õ2.5-fold increase in endocrine tissue at day 56 (p<0.05). From day 0 to day 7 the average rate of change of islet area was 12.7% per day, and this rate decreased to 5.3% per day from day 7 to day 42, and to 2.8% per day from day 42 to day 56. Administration of INGAP [104][105][106][107][108][109][110][111][112][113][114][115][116][117][118] to adult hamsters led to a 31% increase in total beta cell mass at day 30 (p=0.031).From day 0 to day 10 the average rate of beta cell mass expansion was 148 μg/day, whereas from day 10 to day 30 it decreased to 45 μg/day. INGAP 104-118 administration to adult CD-1 mice resulted in an approximately twofold increase in beta cell mass after 31 days (p=0.021). However, at day 90, there was no significant difference vs age-matched control mice (p=0.30), even though the neogenic beta cell mass was approximately fourfold greater (p=0.026). Beta cell replication was decreased by 56% (p<0.048), whereas beta cell apoptosis was fourfold greater (p<0.003) in 90-day INGAP 104-118 -treated mice compared with age-matched control mice. Conclusions/interpretation These data indicate that in the presence of ongoing islet neogenesis, homeostatic regulatory mechanisms intervene to regulate beta cell mass according to the prevailing metabolic requirements.

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Pancreas Transplantation for Treatment of Diabetes Mellitus

Cited by 121 publications

References 63 publications

Improved vascular engraftment and function of autotransplanted pancreatic islets as a result of partial pancreatectomy in the mouse and rat

Improved vascular engraftment and function of autotransplanted pancreatic islets as a result of partial pancreatectomy in the mouse and rat

Pancreas transplant alone has beneficial effects on retinopathy in type 1 diabetic patients

Evidence for the homeostatic regulation of induced beta cell mass expansion

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