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Query: UMLS:C0011849 (diabetes)
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The BB/W strain of rats develop spontaneous insulin-dependent diabetes. Diabetic BB/W rats have a marked insulinopenia and greatly diminished levels of insulin in their pancreas. Using a radioimmunoassay for rat pancreatic polypeptide (PP), we have examined the content of PP in extracts of the total pancreas and also the regional PP concentration of the three pancreatic lobes. Radioimmunoassays for glucagon, somatostatin (SRIF) and insulin were also made on these extracts. Compared with nondiabetic BB/W rat pancreas, pancreatic extracts from severely diabetic BB/W rats contained 30% as much PP, 31% as much glucagon, 19% as much SRIF, and 0.5% as much insulin. The rat PP radioimmunoassay was used to determine the elution pattern of PP-like antigens in gel chromatography fractions and to measure in vitro secretion of PP from perifused pancreatic slices obtained from diabetic and nondiabetic animals. PP-like immunoreactivity was observed in two zones in the elution from the gel columns when extracts from normal or diabetic rats were chromatographed. The major zone of immunoreactivity eluting at the volume expected for intact monometric rat PP accounted for 67% of the PP-like immunoreactivity in the case of nondiabetic rats and greater than 80% of the PP-like immunoreactivity found in extracts from severely diabetic rats. The minor zone of PP-like immunoreactivity eluted at a volume similar to the position of tetradecapeptide SRIF contained the remainder of detected PP-like immunoreactivity. Tissue slices from diabetic rats secreted more PP and glucagon than slices from nondiabetic rats when slices were perifused with a medium containing leucine, carbachol, and cholecystokinin, even though diabetic pancreas has smaller amounts of PP, glucagon, SRIF, and insulin. Stimulated insulin secretion was virtually absent when tissue slices from diabetic rats were perifused. These results indicate that in the BB/W diabetic rat: (a) pancreatic glucagon, PP, and SRIF are moderately decreased and insulin levels are drastically reduced, (b) lower levels of degraded or low molecular weight form of immunoreactive PP occurs in the diabetic rat pancreas compared to the normal rat, (c) the diabetic pancreas secretes more PP and glucagon and much less insulin than pancreas from nondiabetic rats when perifused under stimulating conditions. The diabetes occurring in the BB/W appears to be a severe type I diabetes characterized by reduced content of insulin, glucagon, SRIF, and PP in the pancreas of these animals. However, secretion of glucagon and PP were not reduced in this in vitro system.
Pancreas 1990 Nov
PMID:Pancreatic polypeptide and other pancreatic hormones in spontaneously diabetic BB/W rats. 198 Jul 35

Pancreas grafts, when not rejected, can sustain an insulin-independent state in type I diabetic recipients for indefinite periods. To what extent the metabolic control achieved approaches that of normal individuals, the relationships between graft endocrine and exocrine function, the effect of reversible rejection episodes on subsequent graft function, and the correlation between the results of serial tests of graft function were determined by studies at 1 month, 1 year, and 2 years in a cohort of 39 recipients (29 females, 10 males; mean age (+/- SD), 33 +/- 5 years; mean duration of diabetes, 22 +/- 6 years) of bladder-drained pancreas transplants performed between November 1984 and December 1988. Fifteen patients received a pancreas transplant alone, 8 a pancreas after a kidney, and 16 a simultaneous pancreas/kidney transplant. Graft endocrine function was tested by a 24-hr metabolic profile of blood glucose levels before meals, at 1 and 2 hr after meals, and during the night (14 values in all), by intravenous and oral blood glucose tolerance tests, and by glycosylated hemoglobin levels (HA1 and HA1c). Graft exocrine function was assessed by urine amylase activity (U/hr). The results of the tests in the recipients were subjected to paired comparisons between timepoints and at each timepoint to the results of the same tests in 55 normal nondiabetic control individuals. The means of the mean 24-hr profile glucose (mg/dl) values were significantly lower (P less than 0.05) at 1 and 2 years posttransplant (116 +/- 27 and 115 +/- 15, respectively) than at 1 month (128 +/- 31) in the recipients, but the mean of the mean values in the normal controls (100 +/- 7) was even lower (P less than 0.05). Mean values of individual timepoints during the profile were significantly lower for 6 of the 14 values in the controls than in the recipients. The mean IVGTT K value of the normal controls (-1.9 +/- 0.4%) was significantly lower than the 1-month and 2-year values of the recipients (-1.5 +/- 0.5% and -1.3 +/- 0.6%, respectively), but the comparison with the 1-year value (-1.6 +/- 0.6%) was not significant. The mean glucose levels at zero minutes and between 120 and 300 min of the OGTTs were significantly lower at both 1 and 2 years than at 1 month in the recipients, and the values in the control group were also significantly lower than in the recipients at 1 month but not at 1 and 2 years.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Long-term metabolic function of pancreas transplants and influence of rejection episodes. 203 Dec 83

Pancreatic transplantation for the treatment of diabetes mellitus in man has proved increasingly successful. Between December 1966 and August 1990 2735 pancreas transplants from 141 institutions were reported to the International Pancreas Transplant Registry. For the period 1986 to 1989 the one year graft survival rate in 1,200 patients was almost 70%, a significant improvement over the preceding five years. The commonest techniques for the diversion of pancreatic secretions are bladder drainage, intestinal drainage and duct occlusion with synthetic polymers. The survival rate of pancreas grafts is significantly higher in recipients of simultaneous pancreas and kidney transplants than in recipients of pancreas transplants after kidney transplants and transplants of the pancreas alone. For this reason pancreas transplantation is mainly indicated as an adjunct to kidney transplantation, when the patient must be given immunosuppressive treatment in any case. A steady decline in the rate of technical failures and of serious adverse reactions as a result of immunosuppressive treatment will undoubtedly widen the present indications. In most recipients of a pancreas graft the blood glucose and hemoglobin A1c levels become normal or near normal. No convincing evidence of an ameliorating effect on microangiopathic and neuropathic complications has been obtained so far. On the other hand, it is established that pancreas transplantation may prevent the development of glomerular lesions in a simultaneously grafted kidney. Previously, transplantation of pancreas islets in man has not been successful. In 1990, however, in several insulin-dependent, diabetic subjects the intraportal transplantation of islets isolated from cadaver pancreas resulted in significant insulin production, and, in a few patients, it was possible to stop insulin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Update of pancreatic transplantation. 206 85

A clinical whole organ pancreas transplantation program for patients with insulin-dependent diabetes mellitus complicated by end-stage renal disease was initiated at Henry Ford Hospital in 1987. Five patients have received pancreatic allografts after a previous kidney transplant (phase 1), and six patients had simultaneous pancreas-kidney transplants (phase 2). Ten patients had functioning pancreatic grafts after surgery, and all of them had normal carbohydrate tolerance with appropriate plasma free insulin responses to an oral glucose tolerance test three months after transplantation. As long as 28 months postsurgery six patients remained free of insulin requirements; however, one patient rejected the pancreatic allograft, and three patients died because of cytomegalovirus pneumonia. Two of the latter patients had functioning pancreatic allografts at the time of their demise. These results compare favorably with those of the International Pancreas Transplant Registry which reflects the world experience. Pancreas transplantation is a unique experimental treatment with the potential of restoring euglycemia and improving the prognosis of insulin-dependent diabetic patients.
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PMID:Allogeneic whole pancreas transplantation in insulin-dependent diabetes mellitus. 208 53

Novel islet cell, duct cell, and acinar cell markers have been identified by monoclonal autoantibodies (Maab) derived from prediabetic BB rats. Spleen cells from two rats that both developed diabetes after splenectomy were fused with mouse myeloma cells. A cellular immunoradiometric assay for differential reactivity toward the surface of two closely related, insulin- and non-insulin-producing rat islet tumor cell lines was used to select and clone several IgM-producing hybridomas. The supernatants were finally characterized by two-color immunofluorescence with islet hormone antisera on frozen sections of human, monkey, and rat pancreas. Maab EB52 stained PP cells, but also few A cells on rat pancreas. Maab CA812 identified a subpopulation of islet D cells on rat, human and monkey pancreas. Although the CA812-reactive antigen and somatostatin were coexpressed in most D cells in adult rat pancreas, only a few islet D cells were stained in the newborn pancreas. The CA812-reactive antigen was not detected in somatostatin-producing cells in the duct epithelium. Maab H37 and IF5 selectively stained acinar cells in rat, human, and monkey pancreas, whereas Maab DA39 identified the rat ductal epithelium including the scattered endocrine cells of the ducts. In summary, B lymphocytes producing autoantibodies to pancreatic endocrine, exocrine, and ductal markers are present in prediabetic BB rats and can be detected by use of transformed pluripotent islet cells as target. Such B lymphocytes can be immortalized to produce monoclonal antibodies to study their role in insulin-dependent diabetes mellitus pathogenesis and to clarify the development of the pancreas.
Pancreas 1990 Sep
PMID:Novel islet, duct, and acinar cell markers defined by monoclonal autoantibodies from prediabetic BB rats. 212 46

Diabetic Lewis rats received pancreaticoduodenum allotransplants from Brown-Norway donors. Cyclosporine A (Cy-A) was used in a dose of 10 mg/kg/day for immunosuppression. These transplanted rats (n = 190) were compared with nondiabetic Lewis rats (n = 36), nondiabetic Lewis rats receiving 10 mg/kg/day Cy-A (n = 42), diabetic rats (n = 103), and diabetic rats receiving 10 mg/kg/day Cy-A (n = 45). The percentage area of periodic acid-Schiff (PAS) positive basement membrane (BM) of rectus muscle microvasculature was compared in each of the groups. It was found that the percentage area of PAS positive BM increased markedly over 15 months of uncontrolled diabetes. Cy-A did not have a significant effect on either normal or diabetic skeletal muscle vascular BM. Rats with established diabetes showed some reversal in the percentage area of PAS positive BM, when pancreas transplantation was performed at 9, 12, and 15 months of diabetes. Pancreas transplantation may appear beneficial even after the development of BM thickening of skeletal muscle vascular BM.
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PMID:Effect of pancreatic allografts on vascular basement membrane thickness in the diabetic rat. 214 81

To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive anodal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) micrograms/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) micrograms/L in control subjects (p less than 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) micrograms/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) micrograms/L in control subjects (p less than 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p less than 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.
Pancreas 1990 May
PMID:Immunoreactive trypsin(ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls. The Swedish Childhood Diabetes Group. 218 53

A series of 10 cases of chronic calcifying pancreatitis from central Tunisia are reported. The mean age at presentation was 23 years and the male to female ratio was 1.5. The main clinical manifestations of the disease were abdominal pain (eight cases), weight loss (four cases), and diarrhea (three cases). Diabetes was recorded in four cases. The etiological investigations yielded negative results in all the patients. It is concluded that central Tunisia should be added to the regions where juvenile chronic calcifying pancreatitis of the "tropical type" may be observed.
Pancreas 1990 May
PMID:Juvenile idiopathic chronic calcifying pancreatitis: report of 10 cases from central Tunisia. 218 58

In 14 nonobese patients after acute pancreatitis and with normal oral glucose tolerance, the response of insulin, C-peptide, and pancreatic glucagon after 100 g of oral glucose was assessed. The curves of insulin and C-peptide were significantly raised compared with those of controls, and no difference was found between the response of patients with a negative (n = 8) and a positive (n = 6) family history of type II diabetes. The curves of pancreatic glucagon did not differ from those found in controls. Our results indicate that a normal response to glucose after recovery from an attack of acute pancreatitis is maintained at the cost of increased insulin secretion.
Pancreas 1990 May
PMID:Endocrine pancreatic secretion in patients after acute pancreatitis. 218 59

A case of agenesis of the dorsal pancreas associated with diabetes mellitus and dilated biliary trees was reported. Preoperative diagnosis was made by endoscopic retrograde cholangiopancreatography and computed tomography. Laparotomy revealed a normal head of the pancreas but complete agenesis of the body and tail. Biopsy specimens removed from the head showed normal pancreatic tissue but only fat tissue from the presumed body and tail. This anomaly has rarely been reported in the literature. A thorough review of the literature was made and consideration of differential diagnosis was discussed.
Pancreas 1990 Jul
PMID:Complete agenesis of the dorsal pancreas--a case report and review of the literature. 219 69


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