Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous work has shown that the C57BL/6J (BL/6) mouse strain develops type 2 diabetes after being fed a high-fat, high-simple carbohydrate (HFHSC) diet. In contrast, the AJ mouse strain does not. The aim of the present study was to determine if differences in the insulin secretory characteristics of isolated perifused islets of these animals could help explain why the BL/6 mouse develops diet-induced diabetes. Insulin secretion was assessed as mean integrated area under the curve during 20 min of stimulation with 27.7 mM glucose or 5 mM lauric acid. We found that both glucose- and laurate-stimulated insulin secretions were significantly less in euglycemic BL/6 mice than in the euglycemic AJ mice. The defect in insulin response to glucose, but not laurate, in islets from the BL/6 mouse was exacerbated when the animals were fed the HFHSC diet. These data suggest that the BL/6 mouse has a defective insulin response to glucose, which is exacerbated by a diabetogenic diet.
Pancreas 1995 Aug
PMID:Defective glucose-stimulated insulin release from perifused islets of C57BL/6J mice. 747 81

Simultaneous pancreas-kidney (SPK) or pancreas-after-kidney (PAK) transplantation has been advocated as an alternative to kidney transplant alone (KTA) for type 1 diabetics with end-stage renal disease. Advocates of combined transplant assert that the procedure reduces, prevents, or mitigates secondary complications of diabetes and improves the quality of life (QOL) of recipients. The combined procedures may be accomplished with a relatively low mortality, but the morbidity significantly exceeds that of KTA. The published data did not provide unambiguous support for the contention that SPK or PAK improved or ameliorated the secondary diabetic complications of retinopathy, neuropathy, and nephropathy, and it cannot be reasonably concluded that such benefit is likely to result. The majority of studies of QOL subsequent to combined transplant had significant methodologic deficiencies which made generalizations problematic. Notwithstanding, improvements in objective measures, such as return to employment or school, reduction in medical care requirements, days spent in hospital, social or physical activity, etc, have not been demonstrated for combined transplant; improvements in subjective measures were inconsistently reported. The United Network for Organ Sharing (UNOS) registry indicated that SPK represents 83 percent, and PAK about 8 percent of all pancreas transplants in the United States. Pancreas graft survival data are limited; UNOS reported 3-year survival rates of approximately 65 percent following SPK, and 35 percent after PAK. Renal graft survival following SPK appears comparable to that reported for most cadaver KTA. However, selection of SPK in lieu of KTA with a living-related donor or HLA-matched cadaver kidney may result in significant reduction in expected renal graft survival, in the range of 40-70 percent to as much as 350 percent. A cost-effectiveness analysis (CEA) model compared SPK with KTA and continued insulin therapy. The model employed a wide range of reported charges/payments, and postulated that SPK would provide significant improvements in quality of life. Sensitivity analyses indicated that SPK was equal in cost effectiveness to KTA only in patients who incurred very high annual costs for the treatment of hyper- or hypoglycemia. The literature does not indicate that such patients comprise the majority of SPK recipients. Additional evidence is necessary to unequivocally demonstrate the risks, costs, and ultimate benefits of combined transplant. Such information should include detailed and unambiguous patient selection criteria, prospective comparative studies of the effects of SPK/PAK upon secondary complications and quality of life, and accurate cost data for the transplant procedures and required followup care.
 ...
PMID:Simultaneous pancreas-kidney and sequential pancreas-after-kidney transplantation. 749 5

Pancreas and kidney transplantation is performed in uremic IDDM patients to cure end-stage renal failure and diabetes. Seventy-two simultaneous kidney-pancreas transplantations were performed at our Institution between July 1985 and November 1994. All transplants were performed using heart-beating cadaver donors. The first 25 patients received 26 segmental pancreas according to Dubernard (KPS), whereas the last 46 patients received a whole, bladder-drained pancrea according to Sollinger (KPW). Mean pancreas cold and warm ischemia times were 294 +/- 14 and 44 +/- 2 minutes, respectively, in the KPS group and 660 +/- 37 and 40 +/- 8 minutes, respectively, in the KPW group. Twelve (48%) KPS patients and 19 (41%) KPW patients had postoperative pancreas surgical complications: vascular thrombosis led to graft failure in 5 KPS patients (20%) and 2 KPW patients (4%) (p = 0.01). Pancreatic fistula, hemorrhagic complications, and duodenum-bladder leakage were the surgical complications observed more frequently. Six KPS patients (24%) and 8 KPW patients (17%) underwent reintervention as a consequence of surgical complications. Fifteen KPS patients (60%) and 30 KPW patients (65%) experienced an acute kidney rejection episode, which was steroid-resistant in 14 KPW and 2 KPS patients. The actuarial survival rates for simultaneous kidney-pancreas recipients at one and 4 years were 92% and 84%, respectively, for KPS recipients, and 95% and 88%, respectively, for KPW patients. Kidney actuarial survival rates at one and 4 years were 96% and 76% respectively, for group KPS, and 93% and 89%, respectively, for KPW patients.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Simultaneous kidney and pancreas transplantation at the San Raffaele Scientific Institute: clinical experience and results. 754 47

The role of insulin resistance in the impaired glucose-stimulated insulin release of Zucker fatty rats was investigated using the insulin-sensitizing thiazolidinedione drug pioglitazone. Fatty rats had fasting hyperinsulinemia yet a blunted secretory response to intravenous glucose compared with lean age-matched controls. Islets from fatty rats secreted less insulin (based on islet DNA) in response to high glucose than islets from lean rats but secreted normal amounts of insulin when tolbutamide or alpha-ketoisocaproic acid (alpha-KIC) was the stimulus. Administering pioglitazone for 9 days diminished basal hyperinsulinemia and increased the insulin response to high glucose by fatty rats but not by lean controls. Pioglitazone pretreatment augmented the secretory response by isolated islets to high glucose, alpha-KIC, and tolbutamide. Augmentation of islet insulin release was not associated with reduced plasma glucose concentration, suggesting that altered glycemia was not involved. Pancreas and islet insulin content was greater in fatty rats than in lean controls and was decreased by pioglitazone; hence, insulin stores and glucose-stimulated insulin release did not correlate. Pioglitazone treatment did not affect the rate of islet glucose usage or ATP/ADP in the presence of 2.75 or 16 mmol/l glucose. These data indicate that ameliorating insulin resistance reverses defective glucose-stimulated insulin release by Zucker fa/fa rats. After pioglitazone administration, insulin secretion may be augmented by increased generation of a metabolic coupling factor from glucose or at a later step in the secretory process that is common to both glucose and nonglucose secretagogues.
Diabetes 1995 Aug
PMID:Insulin secretory defect in Zucker fa/fa rats is improved by ameliorating insulin resistance. 762 5

CD4 and CD8 T cells and macrophages have been implicated as cellular mediators of beta cell destruction in insulin-dependent diabetes mellitus (IDDM). The ratios of the two T cell subsets were, therefore, quantified in nonobese diabetic (NOD) mouse islets prior to IDDM, at the onset of the disease, and following onset by immunohistochemistry. The number of periislet-, intraislet-, and exocrine-located macrophages were also determined during these stages. At all time points studied (day 90, day 250, at diabetes onset, 4-6 weeks after diabetes), CD4 cells were 2.5 times higher than CD8 cells except at day 250, on which the CD4:CD8 ratio was 3.8. At days 90 and 250, islets were heavily infiltrated with both the T cell subsets associated with lower numbers of macrophages. At onset of the disease and after insulin treatment, although the CD4:CD8 ratios were similar, the absolute numbers of the two subsets were reduced-considerably. At these stages a majority of the islets was atrophied, some were still surrounded by T cells and macrophages and were enriched with glucagon cells. CD4 and CD8 cells were also observed in the exocrine region at the two stages. Macrophages located in the periislet areas were significantly higher in number than in the intraislet positions in all study groups (p = 0.001). They also showed a gradual decline from day 90 to clinical diabetes. Periislet-located macrophages were significantly higher at day 90 than after onset and in control Swiss mice (p < 0.05). The numbers of macrophages in the exocrine areas were similar in all groups of NOD mice. In control Swiss mice they were significantly lower in the periislet, intraislet, and exocrine regions.
Pancreas 1995 Jul
PMID:Immunohistochemical analyses of pancreatic macrophages and CD4 and CD8 T cell subsets prior to and following diabetes in the NOD mouse. 766 42

Protective effects of essential fatty acid deficiency (EFAD) on autoimmunity were shown in rodents. Our goal was to investigate the mechanisms of EFAD effects on autoimmune diabetes in nonobese diabetic (NOD) mice. Weanling female mice were randomized between a control diet group and an EFAD diet group, and the development of diabetes and immune response was determined over a 6-month period. The cumulative incidence of diabetes was significantly reduced in the EFAD group (20 vs 68.75% in the control group; p < 0.01), without affecting the insulitis process. Splenocyte reactivity to phytohemagglutinin and anti-CD3 antibody was significantly increased in EFAD-fed mice (p < 0.01). The EFAD group also exhibited a dramatic increase in baseline (29-fold) and antigen-presenting cell (APC)-stimulated (10-fold) T cell responses in syngeneic mixed leukocyte reaction. These responses were associated with a marked increase in splenocyte interleukin-4 (IL-4) production, a reduction in interferon-gamma production, and a down-regulation of CD45RB isoform expression. Macrophages in the EFAD group exerted a reduced suppressive effect on concanavalin A-induced splenocyte proliferation and were found to release increased amounts of tumor necrosis factor-alpha and IL-1 and reduced amounts of prostaglandin E2. These results clearly demonstrate that EFAD prevents diabetes in NOD mice. The data suggest an enhanced activity of Th2-like cells, as well as an effect on APC activity linked to alteration in eicosanoid metabolism.
Pancreas 1995 Jul
PMID:Essential fatty acid deficiency prevents autoimmune diabetes in nonobese diabetic mice through a positive impact on antigen-presenting cells and Th2 lymphocytes. 766 43

Viral infection is assumed to trigger or exacerbate autoimmune responses against pancreatic beta cells leading to the development of insulin-dependent diabetes mellitus (IDDM). We therefore examined by polymerase chain reaction the presence of two candidate viruses, cytomegalovirus and Epstein-Barr virus, in IDDM pancreases. Pancreas tissues were obtained by biopsy under laparoscopy from 16 recent-onset IDDM patients: age 17-53 years; disease duration 0-7 months; six had flu-like symptoms before onset. Frozen sections were made and subjected to DNA amplification. DNA samples were prepared from the frozen sections and polymerase chain reaction was performed using primers specific to cytomegalovirus, Epstein-Barr virus and control gene for HLA-DP. Cytomegalovirus- and Epstein-Barr virus-infected cells were used for positive control. Southern blot analysis could detect cytomegalovirus DNA from as few as 2 x 10(-1) cytomegalovirus-infected cells and Epstein-Barr virus DNA from two Epstein-Barr virus-infected cells. This highly sensitive analysis, however, could not detect cytomegalovirus or Epstein-Barr virus genomes in pancreases of recent-onset IDDM. A single copy human gene (HLA-DP) was amplified from all IDDM pancreases indicating that DNA amplification was performed without inhibition. We conclude that cytomegalovirus or Epstein-Barr virus genomes are unlikely to exist in pancreas biopsy specimens of recent-onset IDDM patients.
 ...
PMID:No detectable cytomegalovirus and Epstein-Barr virus genomes in the pancreas of recent-onset IDDM patients. 767 87

The Goto-Kakizaki (GK) rat represents a spontaneous animal model of non-insulin-dependent diabetes mellitus (NIDDM) characterized by impaired glucose-stimulated insulin release from the pancreatic beta cells. To study whether an alteration in their islet beta-cell numbers occurs in parallel with the impairment of insulin secretion in this model, the relative volume density of beta cells was determined by means of conventional point sampling in immunostained 4-microns-thick sections of the pancreata from 8-week-old GK rats. The pancreata of nondiabetic Wistar rats were used as control parenchyma. In the GK pancreata the majority of islets was found to have a normal structure; only a few of the islets demonstrated an irregular shape (starfish-shaped islets) with fibrosis. The relative volume of the total endocrine parenchyma was found to be 2.0 +/- 0.6% (mean +/- SEM) of the whole pancreatic parenchyma in GK rats. In the control rats the corresponding value was 2.3 +/- 0.5%. The islet beta-cell density was also similar in GK and control rat islets, amounting to 75.2 +/- 8.5 and 66.9 +/- 6.6%, respectively. Thus, the total relative volume of beta cells was 1.5 +/- 0.5% in GK rats and 1.6 +/- 0.4% in controls. In conclusion, the density of beta cells is preserved in the pancreata of the young, diabetic GK rats, suggesting the absence of a causal relationship between the relative pancreatic beta-cell volume and the impaired glucose-induced insulin secretion in this NIDDM animal model.
Pancreas 1995 Mar
PMID:Preserved beta-cell density in the endocrine pancreas of young, spontaneously diabetic Goto-Kakizaki (GK) rats. 771 39

Glutamic acid decarboxylase (GAD) is a candidate target autoantigen involved in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). The functional state of the beta cells has been suggested to play a pathogenic role in IDDM by altering beta-cell autoantigen expression. In this study, we investigated expression of GAD-65 and GAD-67 in isolated Sprague-Dawley rat islets cultured at different glucose concentrations. Using GAD isoform-specific antibodies in an immunoblot assay, we found that expression of both GAD-65 and GAD-67 in cultured islets was glucose dependent and that increased expression of both forms of GAD correlated with increased functional state of the beta cell. Our data indicate that the functional state of the beta cell influences islet cell expression of GAD. Thus, decreasing islet cell expression of GAD by suppressing beta cells activity may have a potential role in blunting the autoimmune destruction of pancreatic islet beta cells.
Pancreas 1994 Sep
PMID:Functional state of the beta cell affects expression of both forms of glutamic acid decarboxylase. 780 9

Endocrine cells of the pancreatic and bile duct system of the diabetic rat were characterized with reference to their influence on duct function. In streptozotocin-induced diabetic rats, the endocrine cells showed various changes in number and topographic distribution along the epithelial lining of the duct system. With the exception of insulin cells, which demonstrated a marked decrease, the number of duct endocrine cells generally increased in the duct system of the diabetic animal, particularly in the terminal portion of both the common hepatic and the accessory pancreatic ducts encompassed by the muscle sphincters. Among them, the cells secreting somatostatin, a potential peptide inducing contraction of the muscle sphincter, showed a remarkable increase in the opening portion of the common hepatic and the accessory pancreatic ducts of the diabetic animal. The duct cells producing glucagon and pancreatic polypeptide, the hormones exerting an inhibitory effect on exocrine secretion of duct and acinar cells, also increased significantly in the duct system of the diabetic animal. These results suggest that the duct endocrine cells are closely related, not only to functional properties of the duct system, but also to disorders of the pancreas and biliary tract in diabetes.
Pancreas 1994 Sep
PMID:Endocrine cells in the rat pancreatic and bile duct system: alteration in diabetes. 780 11


<< Previous 1 2 3 4 5 6 7 8 9 10