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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A spontaneously developed endocrine-exocrine pancreatic dysfunction was observed in the aged males of an inbred strain of Wistar rats, WBN/Kob. Nonobese male WBN/Kob rats developed glycosuria and hyperglycemia at around 9 months of age. Cumulative incidence of diabetes in male rats was 43% (33 of 76) at 12 months of age and reached 90% at the age of 21 months. In contrast, female rats did not become diabetic. Urinary excretion of amylase in WBN/Kob rats was significantly increased in comparison with control Wistar rats. Moreover, the exocrine pancreatic function test was impaired in WBN/Kob rats. Pathological examination of pancreata revealed infiltration of inflammatory cells, hemorrhage, deposition of hemosiderin, and fibrinous exudation around pancreatic ducts and blood vessels at 3 months of age. A gradual increase of fibrous tissue into the exocrine tissue and islets was observed with advancing age. The extremely enlarged interlobular lymph nodes were also observed. At the age of 12 months, the fibrous tissue replaced extensive areas of the pancreas and involved islets. The amylase content of pancreata in WBN/Kob rats was markedly decreased in comparison with that in Wistar rats at 12 months of age. Islets composed of few endocrine cells were detected. Immunohistochemical staining for insulin and glucagon showed a decreased number of not only B cells but also A cells. Moreover, both the pancreatic insulin and glucagon contents were markedly decreased in WBN/Kob rats in comparison with Wistar rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Pancreas 1990 Jul
PMID:Diabetic strain (WBN/Kob) of rat characterized by endocrine-exocrine pancreatic impairment due to distinct fibrosis. 169 84

We assessed the heterogeneity in the islet cell cytoplasmic antibody (ICA) response of insulin-dependent diabetes mellitus (IDDM) patients via indirect immunofluorescence on frozen sections of human, bovine, and porcine pancreas. The three substrates detected comparable frequencies of ICA positives among the IDDM sera tested, whereas control sera were ICA negative on all three substrates. However, individual IDDM serum samples showed heterogeneity in ICA binding on the three pancreata. Of 28 sera tested on all three substrates, 22 were ICA positive on human pancreas, three were ICA positive on bovine pancreas, and two were ICA positive on porcine pancreas. Sensitivity of ICA epitopes to neuraminidase treatment and periodate oxidation suggests that glycoconjugates are recognized by serum ICA. Cholera toxin blocked ICA binding. However, the functional cholera toxin receptor ganglioside Gm1 is resistant to neuraminidase treatment and periodate oxidation. Therefore, it is unlikely that Gm1 is the ICA determinant. These data suggest that not all ICA antigens are equivalently expressed on islets from different pancreata and/or that each individual responds to a hierarchy of islet antigens such that restricted patterns of specific ICA binding are found.
Pancreas 1990 Nov
PMID:Heterogeneity in the specificity of the islet cell cytoplasmic antibody response in insulin-dependent diabetes mellitus. 170 23

Conflicting published data regarding the role of macrophages and other cell types during the early stages of diabetes mellitus led us to further study this problem. To this end we diabetized mice, using low doses of streptozocin (STZ), 40 mg/kg body wt/day/5 days, and processed their pancreatic tissue for immunocytochemistry and ultrastructural observations; immunohistochemistry was performed on days 5 and 18 after the first STZ injection, and islets were observed ultrastructurally on days 5, 9, 10, and 18. Animals were tested for fasting serum glucose, and isolated islets were assayed for insulin secretion capacity. Immunohistology demonstrated that expression of major histocompatability complex class 2 antigens is strongly induced by multiple, low dose STZ treatments prior to impaired insulin release, and that different types of cells within the islet are capable of expressing Ia molecules. Ultrastructurally we found (a) a small number of macrophages (most probably resident monocytes/macrophages) containing B-cell debris, that were located close to either damaged or intact B cells; (b) a large number of recruited macrophages in a vascular or perivascular position; and (c) macrophages recognizable in the exocrine portion, close to the islets, occasionally containing exocrine cell debris. This led us to believe that recruited macrophages play an important role in the early islet-infiltrating stage.
Pancreas 1991 Nov
PMID:Further morphological and biochemical observations on early low dose streptozocin diabetes in mice. 178 Mar 26

Evaluation of whole-organ pancreas transplantation in the therapy of IDDM has been difficult because of generally poor graft survival and significant complications in past experience. We report a technically successful simultaneous pancreas/kidney transplant program with patient and graft survival of 85% over 3 years of follow-up (mean 21 months) in 33 subjects with IDDM. Glucose metabolism was normalized without need for exogenous insulin immediately posttransplant in all but one recipient and remained normal in 85% of recipients. The outcome in pancreas/kidney recipients was compared with that in 18 insulin-dependent diabetic recipients of kidney transplant only performed in the same period. Quality of life was assessed with one general and one diabetes-specific questionnaire. General quality of life issues improved significantly in both pancreas/kidney and kidney recipients, but diabetes specific quality of life improved only in the pancreas/kidney recipients. Pancreas/kidney recipients required twice as long a period of hospitalization for the transplant and two times as many readmissions for a variety of complications. Only a minority of hospital admissions was strictly attributable to the pancreas graft. Of the five deaths in the pancreas/kidney recipients, two were attributable to the pancreas transplant. Pancreas transplantation in IDDM can now be accomplished with a high degree of success, resulting in normalized glucose metabolism and with overall mortality similar to kidney transplantation alone. Successful pancreas transplantation improves quality of life with respect to diabetes but this benefit is accomplished at a cost of increased hospital admissions and complications related to the transplanted pancreas. The effects of pancreas transplantation on the long-term complications of insulin-dependent diabetes remain unknown.
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PMID:Long-term metabolic and quality of life results with pancreatic/renal transplantation in insulin-dependent diabetes mellitus. 185 59

Pancreas transplantation is usually performed in patients with denovo type I diabetes, who have advanced secondary complications. We report a case in which whole pancreaticoduodenal transplantation, with enteric drainage, was performed to correct both endocrine and exocrine deficiencies in a patient with hyperlabile diabetes and steatorrhea, unresponsive to oral enzyme replacement therapy, following staged total pancreatectomy for idiopathic or familial chronic pancreatitis. The transplant was performed one year after completion of native pancreatectomy and immediately established an insulin-independent euglycemic state, with normal oral and intravenous glucose tolerance test results and correction of steatorrhea. Beginning one year posttransplant, the patient had intermittent episodes of steatorrhea, associated with mild elevation of blood sugar levels, which were presumed to be due to rejection and, indeed, responded to antirejection treatment with antilymphocyte globulin and temporary increases in steroids dosages. At 20 months posttransplant, steatorrhea did not respond to antirejection treatment and an acute abdomen developed. Laparotomy revealed a perforated graft duodenum, which was resected; pathology showed transmural necrosis secondary to chronic rejection. The pancreas graft itself was left in situ, disconnected from the intestinal tract. The patient remained normoglycemic after graft duodenectomy but resumed oral enzyme replacement therapy in an attempt to combat recurrence of severe steatorrhea. However, his overall situation remained improved compared to pretransplant, since the exocrine deficiency was tolerable in the absence of a diabetic state. Ten months postgraft duodenectomy (38 months posttransplant), elevations in blood sugar levels were treated with another course of antirejection treatment and levels temporarily declined. At 14 months postgraft duodenectomy (42 months posttransplant), graft endocrine function again declined and exogenous insulin was resumed. Six months later, four years after the original transplant, a new enteric-drained pancreaticoduodenal graft was placed, once again resulting in an insulin-independent, steatorrheafree state. With improvements in immunosuppression, pancreas transplantation could be offered to selected patients with hyperlabile diabetes, following total pancreatectomy for benign disease; if the enteric drainage technique is used, in the absence of rejection, exocrine deficiency could be corrected as well.
Pancreas 1991 Jul
PMID:Pancreaticoduodenal transplantation with enteric drainage following native total pancreatectomy for chronic pancreatitis: a case report. 187 4

Pancreas transplantation, when successful, is a reproducibly effective method to normalize glycemia without the use of exogenous insulin treatment in patients with diabetes mellitus. Success rates for combined pancreas and kidney transplantation are approximately 70%, and patient survival rates are approximately 90% 1 yr postoperatively. Metabolic benefits of this procedure include normalization of levels of fasting plasma glucose and HbA1C. Glucose-induced insulin secretion and intravenous glucose tolerance are normalized. Improvements are also observed in glucose recovery after insulin-induced hypoglycemia and in glucagon secretion during hypoglycemia. Pancreas transplantation is also associated with normalization of kidney structure and both motor and sensory nerve function. However, no benefits have been observed with regard to pancreatic polypeptide secretion, kidney function, and the retinal pathology of diabetes mellitus. Pancreas transplantation has reached a point in its history where the operative technique and its ancillary medical therapy have been optimized. Improvement in the rates of success, morbidity, and mortality will probably depend on improvement in immunosuppressive drugs and the physical condition of the recipients themselves. The time is at hand when we need to carefully consider whether it is ethical and advisable to make pancreas transplantation available to individuals who have fewer chronic complications of diabetes mellitus. Future studies of pancreas transplantation must incorporate more rigid experimental controls than have been used in the past to better assess the relative merits of this procedure.
Diabetes 1991 Sep
PMID:Pancreas transplantation in humans with diabetes mellitus. 193 15

We have examined the possibility that selenium deficiency may underlie one or more of the following peculiarities of chronic pancreatitis in tropical as compared to temperate zones: much higher prevalence, propensity for pancreatic calculi, and high frequency of diabetes. Selenium was measured by graphite furnace atomic absorption spectrometry in sera from 20 healthy volunteers, 36 patients with chronic pancreatitis (calcific 35, diabetic 32), and 23 patients with primary forms of diabetes, from Madras, South India; results were compared with data from 41 controls and 37 patients with chronic pancreatitis (calcific 13, diabetes 8) from Manchester, North West, England. We conclude that (a) bioavailability of selenium is equally high in each geographic area; (b) decrement in serum selenium (p less than 0.001) is of a similar order in Manchester and Madras patients, which denies a connection with calculi formation or pancreatic exocrine failure (since the incidence of these two problems was substantially higher in the Madras series); and (c) selenium levels do not account for accelerated course to diabetes in tropical chronic pancreatitis.
Pancreas 1991 Sep
PMID:Selenium and diabetes in the tropics. 194 9

A new kit for radioimmunoassay of serum phospholipase A2 (PLA2) with monoclonal antibody (S-0932, Shionogi, Osaka, Japan) was used to examine PLA2 levels in patients with various diseases. Patients with acute pancreatitis showed significantly increased serum PLA2 levels. In patients with chronic pancreatitis, significant correlations were observed between the levels of factors evaluated by the secretin test and serum PLA2 levels. In patients with pancreatic cancer, serum PLA2 levels varied with disease severity. Serum PLA2 concentrations were within the normal range in patients with other malignant tumors, diabetes mellitus, and chronic liver diseases but were increased in patients with chronic renal failure. S-Sepharose column analysis of sera showed a small peak of pro-PLA2 and a large peak of PLA2 in sera from patients with severe acute pancreatitis, but a large peak of pro-PLA2 in healthy controls and patients with other diseases. On G-100 gel filtration, high-molecular-weight PLA2 immunoreactivity was detected in sera of patients with chronic renal failure, whereas a single peak of PLA2 immunoreactivity coinciding with that of standard PLA2 was detected in sera of patients with acute pancreatitis. These results suggest that (a) measurement of serum PLA2 is clinically useful for diagnosis and monitoring of pancreatitis, (b) active PLA2 in the circulation is dominant in severe acute pancreatitis, and (c) the kidney may be the main site of PLA2 degradation or excretion.
Pancreas 1991 Sep
PMID:Clinical usefulness of serum phospholipase A2 determination in patients with pancreatic diseases. 194 16

We have investigated the influence of non-insulin-dependent diabetes on the regulation of somatostatin secretion from the pancreatic D cell. These results were compared with the concomittantly measured secretory responses from A and B cells. Rats were rendered non-insulin-dependent diabetic by neonatal injection of streptozotocin (STZ). Secretion was studied in perfused pancreas at 6-10 weeks of age. At this age, STZ rats were mildly hyperglycemic, their nonfasting blood glucose being 9.0 +/- 0.8 vs. 5.6 +/- 0.2 mM in control rats. In perfused pancreas from the latter rats, high glucose, i.e., 16.7 mM, stimulated somatostatin secretion but completely failed to do so in STZ rats. Arginine (in the presence of low glucose, i.e., 3.3 mM) moderately stimulated somatostatin secretion in controls but fourfold more in STZ rats. Preperfusion with high glucose markedly potentiated subsequent arginine-induced somatostatin secretion in controls but failed to do so in STZ rats. Basal glucagon release was inhibited by ambient high glucose in control and STZ rats alike. Arginine-induced glucagon release was profoundly inhibited both by ambient and previous exposure to glucose in controls but only slightly and nonsignificantly in STZ rats. The insulin response to high glucose in controls was reduced by 90% in STZ. The insulin response to arginine (in the presence of low glucose) was 3.3-fold enhanced in STZ. Ambient and previous high glucose markedly enhanced arginine-induced insulin secretion in controls but only moderately so in STZ rats. We conclude that already mild hyperglycemia is associated with marked D-cell insensitivity to glucose that is qualitatively similar to A- and B-cell insensitivity.
Pancreas 1990 May
PMID:Abnormal regulation by glucose of somatostatin secretion in the perfused pancreas of NIDDM rats. 197 41

This study describes the sequential morphological changes in pancreatic islets from 1-, 6-, and 18-month-old male eSS rats, as compared to aged-matched control animals. Spontaneous diabetes mellitus was confirmed in 6- and 18-month-old eSS rats after an oral glucose tolerance test. Light microscopic immunocytochemical and morphometric techniques were used to study islet-cell populations. The pancreas was normal, and the morphometric methods did not reveal significant changes in islets from 1-month-old rats. However, 6-month-old eSS animals showed disruption of islet architecture and fibrosis in the stroma. The volume density (Vvi) of endocrine tissue and the Vvi and percentage of B cells were increased, whereas the Vvi of exocrine tissue and the Vvi and percentage of A cells were diminished. Eighteen-month-old eSS rats also exhibited conspicuous islet lesions. Nevertheless, the Vvi of endocrine tissue and the Vvi and percentage of B cells were diminished, while the Vvi of exocrine tissue and the Vvi and percentage of D cells were increased. Our results provide further quantitative evidence for the sequential morphological events occurring in the pancreatic islets of a useful animal model of diabetes mellitus.
Pancreas 1990 Sep
PMID:Sequential morphological changes in pancreatic islets of spontaneously diabetic rats. 197 14


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