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

In screening a rat pancreatic islet cDNA library by differential hybridization for transcripts increased by glucose, the H chain of ferritin, an iron storage protein, was identified. An ELISA for rat ferritin showed that the insulin cell contains a surprisingly high amount of ferritin comparable to that of iron storage tissues. Most of the ferritin was located in the beta cell, as judged from colocalization of ferritin and insulin by immunohistochemical staining of the pancreas. Islets maintained for 24 h in culture medium containing 20 mM glucose are capable of releasing insulin in response to stimulation with glucose, but islets maintained at 1 mM glucose are incapacitated in response to glucose (see ref 1). Immunoassayable ferritin was threefold higher in 20 mM glucose islets than in 1 mM glucose islets and the glucose-stimulated increase in H ferritin mRNA was confirmed by probing Northern blots of islet RNA with authentic H and L chain cDNAs. This showed that H ferritin mRNA was four- to eightfold higher in 20 mM-glucose islets than in 1 mM glucose islets, whereas L ferritin mRNA was decreased 75-90% in 20 mM glucose islets relative to 1 mM glucose islets. The physiological reason for the abundance of (apo)ferritin in the beta cell is not readily apparent because the islet contains very little iron. Whether or not ferritin is used to handle another metal such as zinc, which is plentiful in the beta cell, is unknown. Another potential reason for ferritin in the beta cell is that ferritin has antioxidant properties and the beta cell is particularly sensitive to oxygen radicals. Regardless of its physiologic purpose, the high amount of ferritin can explain why iron is preferentially retained in the insulin cell and causes diabetes in diseases of iron overloading.
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PMID:Large amount of (apo)ferritin in the pancreatic insulin cell and its stimulation by glucose. 805 Jun 78

During the period 1986-93 22 patients were diagnosed as having primary hemochromatosis. Only 11 of them had elevated aminotransferases. Transferrin saturation was higher > 63% in 17 (77%) and serum-ferritin was higher in all the patients. (257 mumol/l to 6,500 mumol/l). A percutaneous liver biopsy was performed in 20 patients, all of whom showed a characteristic grading from 2 + to 4+ using Perls' stain. Two males had cirrhosis with simultaneous hepatocellular carcinoma, and another two had cirrhosis. One patient had diabetes mellitus type I. We conclude that fasting serum-iron and transferrin should be determined in all subjects over 40 years of age and in patients with chronic elevation of liver enzymes. If transferrin saturation is higher than 50% in females and 60% in males, serum ferritin should be determined. A percutaneous liver biopsy should be performed if both values are higher than normal. Screening of siblings is important because of the autosomal recessive pattern of inheritance.
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PMID:[Clinical experience with early hemochromatosis]. 807 82

Erythropoietin (EPO) given subcutaneously (SC) once per week has been successful in the treatment of anemia in continuous ambulatory peritoneal dialysis (CAPD) patients. We have identified a population of CAPD patients that requires EPO administration once per week or less often. To determine if specific variables could be identified that would predict which CAPD patients would require infrequent EPO dosing, we reviewed the charts of all our CAPD patients who were receiving EPO as of 1 June 1992. Patients had to have been on CAPD for 3 months and EPO for 3 months to be considered for analysis. We identified 12 patients who required EPO once per week or less frequently (infrequent EPO) and 9 patients who required EPO more than once per week (frequent EPO). Parameters that were analyzed included age, gender, race, time on CAPD, history of gastrointestinal bleeding, exit-site infection or peritonitis in the last 60 days, diabetes, amount of dialysate instilled per day, and the number of exchanges per day. Laboratory data that were analyzed included hemoglobin, hematocrit, serum iron, total iron-binding capacity, ferritin, blood urea nitrogen (BUN), creatinine, BUN/creatinine ratio, albumin, total protein, parathyroid hormone, and aluminum. Categorical data were analyzed via chi-square, and numerical data were analyzed via the t-test. The infrequent EPO group required only 35% as much EPO as the frequent group to maintain hemoglobin and hematocrit, which were significantly greater. The only parameter that was different between the two groups was age (infrequent EPO 42 +/- 13.2 vs frequent EPO 55.8 +/- 11.9 years, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Infrequent dosing of subcutaneous erythropoietin for the treatment of anemia in patients on CAPD. 810 57

An elevated serum ferritin concentration recently has been shown to be associated with coronary artery disease and its risk factors, including blood glucose concentration. The purpose of this study is to establish the prevalence of elevated levels of serum ferritin in patients with non-insulin-dependent diabetes mellitus (NIDDM) without hemochromatosis and to determine whether or not deferoxamine is of therapeutic value in treating such patients. The level of serum ferritin was measured in consecutive eligible patients with NIDDM seen at routine outpatient visits. Five patients with an elevated serum ferritin were treated with deferoxamine, 1 g intramuscularly, twice a week for 12 weeks. The level of serum ferritin was measured every 4 weeks, and the level of glycosylated hemoglobin was measured at baseline, at the end of the treatment, and 12 weeks after treatment was completed. The level of serum ferritin was elevated in 34 of 102 (33%) patients with NIDDM. The level of serum ferritin remained elevated in 30 of 32 (94%) of these patients on repeat testing. In three of the five patients treated with deferoxamine, the level of serum ferritin was normalized, but no patient had an appreciable change in dosage of medication for diabetes or glycemic control. Non-insulin-dependent diabetes is a condition frequently associated with elevated levels of serum ferritin. Treatment with deferoxamine intramuscularly was not effective in improving control of glucose in our patient group.
J Diabetes Complications
PMID:Non-insulin-dependent diabetes mellitus and elevated serum ferritin level. 821 68

Neurophysiologic investigations were performed in 34 Chinese patients with beta-thalassemia major maintained on long-term desferrioxamine treatment to look for subclinical toxicity in the auditory, visual, peripheral, or central neural pathways. In the auditory pathway study, four patients (12%) had mild sensorineural hearing impairment. Two patients (6%) had increased P 100 latencies in the visual evoked potential study, and nine patients (26%) had abnormal electroretinogram results. All had normal electrooculograms. Ophthalmoscopic examination was abnormal in three patients (9%), and three (9%) had a visual field defect. In the peripheral or central nervous pathways, seven patients (21%) had sensory neuropathy, of which three cases were probably related to diabetes mellitus. All had normal motor conduction velocities. Four patients (12%) had increased cortical latencies of median or posterior tibial somatosensory evoked potential. Abnormalities in multiple neural pathways were seen in four patients (12%). There was a significant association between subclinical toxicity to the peripheral or central nervous systems and serum ferritin level (P < .03) and the presence of diabetes mellitus (P < .002). There was no significant relationship between the age, dosage, or duration of desferrioxamine used and the increased risk of neurotoxicity to the auditory, visual, peripheral, or central nervous systems. There was also no association between the risk of neurotoxicity and the serum zinc, copper, or fructosamine levels.
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PMID:Neurophysiologic study of beta-thalassemia patients. 822 27

Iron overload is a major cause of morbidity and mortality in thalassemia major patients. All chronic liver diseases may be associated with such endocrine symptoms as diabetes mellitus, testicular failure or hypothyroidism. We studied 15 thalassemic patients (12 men and 3 women; age range: 10-50 years, mean: 22.5 years). All patients received blood transfusions, but only some were treated with iron chelation. Seven patients were splenectomized. MRI was performed with an 0.5 T superconducting magnet, using SE T1- and T2-weighted and IR sequences. We used these data with Bloch's equation to calculate T1 and T2 values. Quantitative analysis was made by calculating signal intensity and relaxation times in 8 hepatic regions of interest: marked reduction in hepatic signal intensity and a negative relationship between T1 and serum ferritin (r = 0.646, p < 0.01) and between T2 and serum ferritin (r = 0.688, p < 0.01) were observed. Moreover, a negative relationship was found between hepatic signal intensity and aspartic aminotransferase (r = 0.524, p < 0.05). Our results confirm the value of MRI in the diagnosis and evaluation of hepatic iron overload but an accurate quantitative analysis can be made only when hepatic iron levels are between 1 and 2 mg/g of liver. Even though it is below statistical significance, the negative relationship between signal intensity and aspartic aminotransferase suggests that hepatic hemochromatosis can influence pituitary-thyroid axis and interfere with peripheral hormone metabolism.
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PMID:[Secondary hepatic hemochromatosis: diagnosis and quantification with 0.5 T magnetic resonance. Value and limitations]. 829 5

With respect to the inverse association of serum ferritin level (SFL) with the risk of gastric cancer (GC) observed in some recent epidemiologic studies, possible mediation by achlorhydria as well as atrophic gastritis (AG), both of which are strongly associated with GC risk at not only the individual but also the population level, was examined in a cross-sectional study of 634 men aged 40 to 49 years randomly selected from 5 populations in Okinawa, Iwate, Nagano, Akita and Tokyo. AG and achlorhydria were serologically diagnosed based on the criteria of pepsinogen (Pep) I level < 70 ng/ml and Pep I/Pep II ratio < 3.0, as described previously, and a serum gastrin level of over 140 pg/ml, respectively. In the results, while the mean SFL for all the subjects differed significantly by area, similar areal differences in SFL were also found even when only the non-AG cases were considered. However, both of the above differences were eliminated with the exception of those between Okinawa and each of the other 4 areas, when adjustments were made for medical histories of diabetes mellitus, ulcers and liver disease, body mass index and gamma-glutamyltranspeptidase level. Therefore, no correlation among the 5 areas was observed between the adjusted areal mean SFLs and GC mortality in either case.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does high gastric cancer risk associated with low serum ferritin level reflect achlorhydria? An examination via cross-sectional study. 840 48

Deferoxamine has been proposed as a potentially important therapy for individuals with NIDDM and mild elevations in serum ferritin. Previously, iron chelation therapy with intravenous deferoxamine over a 5-13-wk period has been reported to normalize serum ferritin and markedly improve glycemic control. To confirm these results and to study potential beneficial effects of deferoxamine on insulin secretion, 9 individuals with NIDDM and elevated serum ferritin levels were treated twice weekly with deferoxamine infusion, following a previously described protocol. Although 8 of 9 subjects achieved normal or near-normal serum ferritin values after deferoxamine therapy, we found little evidence that it produced beneficial effects on glycemic control. Fasting glucose levels pre- and post-deferoxamine therapy were unchanged (11.6 +/- 1.2 and 11.3 +/- 1.5 mM, respectively, P = 0.80). GHb levels declined slightly after deferoxamine therapy (9.3 +/- 0.7 vs. 8.8 +/- 0.7%, P < 0.05); however, this effect was small and was not associated with elimination of or even substantial reduction in insulin or oral hypoglycemic therapy. Deferoxamine therapy did not significantly alter fasting insulin or C-peptide levels, nor stimulated insulin or C-peptide responses to intravenous arginine or glucose. During follow-up studies 1.5-8 mo after deferoxamine therapy, serum ferritin levels again were elevated in 5 of 8 subjects who showed an initial response. Thus, although deferoxamine therapy reduced serum ferritin levels in our subjects, we were unable to confirm a previous report that this effect was associated with any meaningful improvement in glycemic control or insulin secretion.
Diabetes 1993 Apr
PMID:No effect of deferoxamine therapy on glucose homeostasis and insulin secretion in individuals with NIDDM and elevated serum ferritin. 845 4

We report a case of aplastic anemia complicated with secondary hemochromatosis after allogenic bone marrow transplantation (BMT). A 29-year-old man was diagnosed as having aplastic anemia at the age of 8. At the age of 28, BMT was performed from his HLA-identical sister. Total volume of blood transfusion before BMT was about 28,000 ml, and in three months after BMT was 8,000 ml. The transplantation was successful, but one month after BMT, dry eyes, skin pigmentation and hepatomegaly appeared. Serum bile duct enzymes and ferritin also increased remarkably. Moreover after thirteen months, glucose tolerance impaired seriously. Abdominal computed tomography (CT) revealed atrophic pancreas and an increased CT density in the liver and the tail of the pancreas. A large amount of iron deposition were also found in liver and stomach biopsy specimens. We concluded that diabetes mellitus was due to secondary hemochtomatosis in the present case. There is a possibility that tissue damage due to iron deposits may have been accelerated through BMT in this patient with a history of many blood transfusions.
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PMID:[Aplastic anemia complicated with secondary hemochromatosis after allogenic bone marrow transplantation]. 853 29

In the search for diabetes genes, the combined approaches of positional cloning with random markers and subsequent evaluation of candidate genes mapping to areas of interest will be increasingly used. For islet candidate genes of unknown function, expressed trinucleotide (triplet) repeats represent a unique subset. It is unlikely that abnormal expansion of expressed islet triplet repeats would be a major cause of diabetes, yet the triplet repeats are frequently polymorphic and can thus be used to map the genes in the human genome. In this study, a human islet cDNA library was screened with (CGG)7 and (CAG)7, and 23 triplet repeats were isolated. Sequencing revealed four known and six novel islet genes containing 4-15 triplet repeats. The four known cDNAs included ferritin, the major iron-binding protein in cells; HSGSA2R, a full-length clone of the alpha-subunit of the G-regulatory protein; HUMSATB1A, a DNA-binding protein expressed predominantly in thymus; and HUMPPA-PRO, a ribosomal protein. The triplet repeats in ferritin and HUMPPAPRO were found to be monomorphic. Characterization of the six unique novel expressed islet triplet cDNAs revealed that they were 0.6-1.5 kb in size, contained 4-15 triplet repeats, and were expressed in islets and all other tissues examined. Four of the novel clones, CGG-isl 10, CGG-isl 11, CAG-isl 6, and CAG-isl 7, were mapped to human chromosomes 19, 16, 12, and 3, respectively, via somatic cell hybrids. One islet cDNA, CAG-isl 7, contained a repeat that was highly polymorphic, with 14 alleles (4-18 triplets) in African-Americans (heterozygosity = 0.86) and 6 alleles (heterozygosity = 0.77) in whites. Northern analysis indicated that the mRNA was abundant in pancreatic islets. A putative full-length clone contained an open reading frame encoding 213 amino acids with a variable number of alanines (4-18) within the COOH-terminal. The gene was uniquely mapped with odds > 1,000:1 on chromosome 3p in Centre d'Etude du Polymorphisme Humain pedigrees. There were no differences in CAG-isl 7 allele frequencies between African-American patients with NIDDM (n = 108) and control subjects (n = 116), nor was expansion above 18 repeats noted. Linkage analysis in 14 nonglucokinase maturity-onset diabetes of the young pedigrees showed a cumulative logarithm of odds score of -33.19 at theta = 0.00. Abnormal expansion was not observed in 20 IDDM patients with one NIDDM parent. While these data suggest no major role for CAG-isl 7 in diabetes, at least four of the six novel islet triplet genes are coexpressed in pancreatic islets and neural tissue, and these genes can now be considered as candidates for diabetes and/or neuropsychiatric diseases.
Diabetes 1996 Feb
PMID:Identification of trinucleotide repeat-containing genes in human pancreatic islets. 854 59


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