The expression of Gal -(1,3)Gal ( Gal) on porcine islet cells remains controversial. Several groups have reported that porcine islet endocrine cells do not express Gal while we have shown in neonatal porcine islets (NPI) that cells do express this antigen. We hypothesize that endocrine cells expressing Gal on NPI are less mature cells that may have originated from ductal cells and that expression of this antigen disappears as they develop into fully mature cells. Thus, we further examined Gal expression on various porcine islet cell preparations and correlated this with the proportion of cytokeratin 7 (CK7)-positive ductal cells. In vitro and in vivo expression of Gal and CK7 was significantly (P<0·05) higher in less mature NPI cells compared with matured NPI and adult porcine islet cells while the reverse was observed in the proportion of cells. Moreover, a significantly higher proportion of CK7-positive cells was detected in the Gal-expressing population compared with non-expressing cells. In contrast, a higher proportion of cells was observed in the Galnegative population compared with the Gal-positive population. These data showed a reduced expression of Gal and CK7 as porcine islet cells mature into cells suggesting a possible role for Gal in the maturation of pancreatic endocrine cells.
The intraportal injection of human pancreatic islets has been indicated as a possible alternative to the pancreas transplant in insulin-dependent diabetic patients. Aim of the present work was to study the effect of intraportal injection of purified human islets on: ( a ) the basal hepatic glucose production; ( b ) the whole body glucose homeostasis and insulin action; and ( c ) the regulation of insulin secretion in insulin-dependent diabetes mellitus patients bearing a kidney transplant. 15 recipients of purified islets from cadaver donors (intraportal injection) were studied by means of the infusion of labeled glucose to quantify the hepatic glucose production. Islet transplanted patients were subdivided in two groups based on graft function and underwent:
This review provides the results of a recent analysis of the Islet Transplant Registry on clinical adult islet transplants performed worldwide through June 30, 1992. Between December 12, 1893 and June 30, 1992, 167 adult islet transplants were performed at 25 institutions worldwide, including 104 at 9 institutions in North America, 62 at 15 institutions in Europe, and 1 elsewhere. The total number of diabetic patients reported to be insulin independent after adult islet allotransplantation through June 30, 1992, was 19. In an analysis by era, the percentage of patients that showed positive basal C-peptide levels (i.e., > or = 1 ng/mL at > or = 1 mo) posttransplant, and that became insulin independent (> 1 wk) in the 1985-1989 era (n = 35 cases) were 20% and 6%, and in the 1990-1992 era (n = 69 cases) were 64% and 20%, respectively, and thus have improved significantly (p < 0.001 and p < 0.05). For the 1990-1992 period, the percentage of patients who showed positive basal C-peptide levels post-transplant, and who became insulin independent in the single donor pancreas group (n = 31 cases) were 52% and 13%, and in the multiple donor pancreata group (n = 36 cases) were 75% and 28%, respectively. Islet graft function rates were nearly identical for grafts prepared from pancreata stored < or = 6 h (n = 27) and > 6 < or = 12 h (n = 29), so that 67% and 72% showed positive basal C-peptide levels, and 30% and 21% of the recipients became insulin independent, respectively. No single patient showed islet graft function sufficient to allow withdrawal from insulin, if the pancreata have been stored for more than 12 h. In regard to recipient category for the six groups, namely IAK (islet after kidney), SIK (simultaneous islet kidney transplantation), SIL (simultaneous islet liver transplantation), SIL(C) (simultaneous islet liver transplantation after cluster operation), SIKL (simultaneous islet kidney liver transplantation), and SIH-L (simultaneous islet heart-lung transplantation), the number of patients who showed positive basal C-peptide levels post-transplant was 11 (58%), 17 (57%), 5 (83%), 8 (80%), 1 (50%), and 0 (0%), and the number of insulin independent patients was 4 (21%), 4 (13%), 0 (0%), 6 (60%), 0 (0%), and 0 (0%), respectively. Comparing the two largest recipient categories, namely IAK and SIK, no difference in the outcome of these transplants was apparent.(ABSTRACT TRUNCATED AT 400 WORDS)
The realization that conventional treatment of insulin dependent diabetes mellitus (IDDM) with diet and insulin injections is apparently insufficient to prevent and even stabilize the secondary complications of diabetes generated interest in endocrine pancreas replacement therapy with the hope that normoglycemia achieved by the replacement of normal functioning islets may prevent, stop or even reverse late diabetic complications.Endocrine pancreas replacement has been attempted by either transplantation of vascularized pancreatic grafts or by transplantation of isolated islets of Langerhans as free grafts. Present situation in pancreas organ transplantationAlthough the clinical experience with islet transplantation is emphasized in this report, a brief overview on what can be achieved by pancreas transplantation will be given in advance. During the last years there has been substantial progress in the field of vascularized pancreatic transplantation, and the results now begin to approach those obtained with other vascularized organ grafts {Sutherland ). In an analysis of 1001 pancreas transplants reported to the International Pancreas Transplant Registry since 1966, 1-year actuarial graft function (insulin independent) and recipient survival rates were 35% and 75% respectively and in an analysis of the periods from 1966 to 1977 (n=64), 1978 to 1982 (n=201), 1983 to 1984 (n=298), and 1985 to 1986 (n=438), 1-year actuarial graft function rates were 3%, 21%, 39%, and 44%. Of the 329 grafts that were functioning at the time of analysis, 169 were less than 1 year posttransplant, whereas 160 were more than 1 year posttransplant, including 16 that were more than 4 years, the longest being 8.2 years (Sutherland and Moudry 1987b).With regard to the disappointing 4-year pancreas function rate the question arises as to whether the inevitable risk of vascularized pancreas transplantation can be justified. Beneficial influence on complications such as retinopathy, neuropathy, and peripheral vascular disease in patients with a successful pancreas transplant has not been convincingly demonstrated (Gray and Morris 1987). A recent study of the Minnesota group (Ramsay et al. 1988) provides evidence that pancreas transplantation and subsequent normoglycemia over 24 months in patients with type 1 diabetes of long duration (mean, 21 years) neither reverses nor prevents the progression of diabetic retinopathy. Solders et al. (1987) have presented data indicating that diabetic neuropathy is not reversed by successful pancreas and renal transplantation.Furthermore, it has not yet been proven that patient survival rate and quality of life are significantly better after simultaneous pancreas and kidney transplantation in recipients with end-stage diabetic nephropathy (ESDN) than in those ESDN-patients with kidney grafts alone. Interest in application of pancreas transplantation to nonuremic, non-kidney-transplant recipients is increasing, because preliminary evidence (Ramsay et al. 1988) suggests that a salubrious effect on late compli...
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