Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iloprost is a chemically stable analogue of prostacyclin, with similar vasodilator and anti-platelet actions. Platelet sensitivity to the inhibitory action of Iloprost has been tested in vitro. Platelet-rich plasma from six healthy subjects and from six patients with type 1 diabetes mellitus was incubated with different concentrations of Iloprost, and then stimulated with ADP (at threshold aggregating concentration) and collagen 4 micrograms/ml. The half-maximal inhibitory concentration (IC50) of Iloprost was calculated and no differences were found between patients and controls. The results of this study suggest that diabetic patients without complications do not differ from healthy subjects in their platelet sensitivity to Iloprost.
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PMID:Platelet sensitivity in vitro to the prostacyclin analogue iloprost in diabetic patients. 248 Mar 23

The role of metformin on platelet aggregation was studied in subjects affected by relatively well controlled type 1 diabetes. 1700 mg of metformin were added to their usual daily treatment; nothing else was changed. Patients were trained to monitor their own glycaemia and presence of degenerative retinopathy was proved. Before the administration of metformin and on day 21, the platelet induced by 1.25, 2.5 and 5 mumol of ADP and by collagen was studied. Fibrinogen, cholesterol, triglycerides, glycosylated haemoglobin and mean blood glucose levels did not show any significant modification after treatment but the maximum aggregation induced by ADP was significantly decreased; the inhibition of aggregation was particularly sensitive for low doses of ADP. No significant correlation was found between the variations in metabolism data and the reduction of the amplitude of platelet aggregation. Metformin, added to the usual treatment undergone by a diabetic treated with insulin, seems to affect platelet aggregation independently of other metabolic factors.
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PMID:Study of the effect of metformin on platelet aggregation in insulin-dependent diabetics. 270 18

Platelet aggregate ratios (PAR) were determined, and threshold concentrations (ED50) of epinephrine, adenosine diphosphate (ADP), and collagen were estimated by platelet aggregometry in 88 IDDM and 52 NIDDM patients without hyperlipidaemia or azotaemia, and in 106 healthy volunteers to revise the question of hyperaggregability in diabetes. ED50-s showed a tendency for negative correlation with age, significant in female but not in male controls. Similar trends were obtained in IDDM and NIDDM females, but were not in IDDM and NIDDM males. The ED50-s of different aggregating agents positively correlated with each other. ED50-s were higher in men than in women in both controls and IDDM patients. Similar but minor differences were observed between women and men in NIDDM. IDDM patients had significantly lower PAR and collagen ED50, and a tendency for epinephrine and ADP to be lower as compared to the sex- and age-matched controls. The differences of PAR were the same, while those of ED50-s were diminished in older NIDDM patients compared to the matched controls. It is concluded, that the previously observed general hyperaggregability in diabetic patients may have partly resulted from sex- and age differences. Threshold concentrations should be compared to sex- and age-matched controls.
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PMID:Sex- and age-dependence of platelet aggregation in diabetes mellitus. 341 60

We studied 24 skin biopsies of the hand in 24 IDDM patients followed at the National Institute of Endocrinology (NIE). Biopsies of 7 healthy individuals were used as controls. The diabetics were divided into two groups, with limited joint mobility (LJM) and without LJM. We compared the different structural components of the skin, and their changes; we used quantitative, semi-quantitative and qualitative methods. We found that patients with LJM had a greater levelling, less rete pegs and dermal papillae (p less than 0.05), increased alteration of the mucopolysaccharides distribution (p less than 0.005), higher frequency of alterations of the elastic fibers (p less than 0.05) and collagen (p less than 0.005), vessel enlargement (p less than 0.025) acquiring cord shape, and reduction of the vessel lumen (p less than 0.005) in comparison with patients without LJM and controls. This could be a consequence of the chronic hyperglycemia from childhood that affects the structure, architecture and function of collagen fibers. Genetic and immunologic studies could help to elucidate the mechanisms of this alteration.
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PMID:Histological and histochemical skin changes in insulin-dependent diabetic patients with and without limited joint mobility. 363 May 33

Patients with insulin dependent diabetes mellitus (IDDM) and limited joint mobility (LJM) were studied to determine if altered respiratory mechanics were another manifestation of a generalized disturbance in collagen metabolism. Lung volumes and maximal expiratory flow volume curves were measured in 23 patients with IDDM. Patients were divided into 2 groups: (1) 11 without LJM, and (2) 12 with severe LJM. The groups were matched for age, sex, and glycemic control but not for duration of IDDM. In patients with severe LJM, forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were significantly decreased (p less than 0.05). Total lung capacity (TLC), thoracic gas volume (TGV) at functional residual capacity (FRC) and residual volume (RV) were also significantly lower (p less than 0.05) in the severe LJM group. There was no evidence of air-flow obstruction in either group. Our results demonstrate an association between severe LJM and a significant decrease in lung volumes. This could be due to decreased lung compliance or restriction of chest wall expansion.
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PMID:Pulmonary function in insulin-dependent diabetes mellitus with limited joint mobility. 649 71

We examined type IV collagen distribution and density in human diabetic kidneys by quantitative immunogold electron microscopy. We studied normal kidney transplant donors and "slow-track" and "fast-track" insulin dependent diabetic (IDDM) patients. The "slow-track" patients had IDDM for > or = 20 years and mesangial volume fraction (VvMes/glom) of < or = 0.32. The "fast-track" patients had IDDM for < or = 20 years and VvMes/glom > or = 0.37. Renal biopsies were embedded in Lowicryl, reacted with polyclonal anti-type IV collagen (in the distribution of the classical alpha 1(IV) and alpha 2(IV) collagen chains) and monoclonal anti-alpha 4(IV) collagen chain antibody followed by gold conjugated secondary antibody. We found, by morphometric techniques, a decrease in the immunogold densities of anti-type IV collagen in the subendothelial zone of the GBM in the "fast-track" IDDM patients. There was a trend towards a decrease in mesangial matrix (MM) particle density in the "fast-track" (P = 0.07) but not in the "slow-track" patients. However, because of the marked increase in MM in the "fast-track" patients, the per glomerulus estimated quantity of these antigens in MM was increased. In contrast, the density of alpha 4(IV) collagen chain was increased in the epithelial zone of the GBM in the "fast-track" IDDM patients. It is not known whether these changes in glomerular type IV collagen represent markers of advanced diabetic lesions or whether these changes might be detected earlier in diabetic patients destined for the later development of serious lesions.
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PMID:Glomerular distribution of type IV collagen in diabetes by high resolution quantitative immunochemistry. 816 29

Several obstacles have hindered the successful transplantation of islets of Langerhans to human patients in efforts to cure type I diabetes mellitus. One problem is the necessity for short- and long-term storage of islets after isolation and before transplantation. Current long-term storage methods, such as incubation in a physiological medium and cryopreservation, are suboptimal, resulting in significant loss of viable islet mass or function. Better storage methods are needed. In this study we examined the long-term storage of rat islets in macrobeads composed of agarose and collagen. Islets isolated from Wistar-Furth rats were placed into macrobeads (1000 islets/macrobead) and maintained in culture for periods of up to 189 days at 37 degrees C. Insulin released from the cultured macrobeads remained constant for periods of at least 154 days. In one group, insulin release was 1050 mU/24 hr/4 beads on day 3 and 1040 mU/24 hr/4 beads on day 154. In another group, insuling release was 1305 Xenotransplantation of Wistar Furth islet macrobeads, stored for 10 to 112 days at 37 degrees C, degrees C into 42 B6AF/1 mice with streptozotocin-induced diabetes resulted in a return to euglycemia in the recipients within 24 hr. Thereafter, euglycemia was maintained for more than 100 days in 32/42 of the recipients, and removal of the macrobeads caused a return to hyperglycemia within 48 hr in all animals. In addition, a group of 7 mice receiving macrobeads containing 1000 islets stored for 84 days had normal glucose tolerance tests (compared with those of 7 nontreated, nontransplanted mice with streptozotocin-induced diabetes and 7 normal mice), demonstrating that the islets in the macrobeads were functioning as they would in an intact pancreas. Finally, 5 macrobeads transplanted after initial storage of 112 days, removed from the first recipient after 100 days or more, stored again for 4 days in vitro, and retransplanted into 5 other diabetic mice also restored and maintained euglycemia for at least 45 days. Our results indicate that collagen-agarose macrobeads are capable of preserving rat pancreatic islets for extended periods without loss of in vitro insulin release capability or ability to achieve and maintain euglycemia in vivo. As such they should be useful for human islet transplantation efforts.
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PMID:Long-term preservation of islets of Langerhans in hydrophilic macrobeads. 861 Mar 76

Extracellular matrix plays an important role in many physiological functions and its abnormalities are thought to play a key role in the pathogenesis of diabetic complications. In this paper we used the techniques of electron microscopy, immunostaining and X-ray diffraction to document some of the early events in the changes of extracellular matrix in a model of insulin dependent diabetes in baboons. Our results show that thickening of basement membrane and enlargement of mesangium are demonstrable in the glomeruli of prepubertal diabetic baboons within 2 years from the onset of diabetes. Concomitant with this was the accumulation of type IV collagen and laminin in the mesangium. By contrast, even the very sensitive technique of X-ray diffraction failed to demonstrate changes in the equatorial direction of collagen molecules of the skin and tendon. We conclude that changes of glomerular extracellular matrix are demonstrable early in insulin dependent diabetes even in prepubertal baboons. These can be used as endpoints in evaluating the efficacy of pharmacological agents such as aminoguanidine in preventing diabetic complications.
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PMID:Changes of extracellular matrix in a baboon (Papio hamadryas) model of insulin dependent diabetes: studies using electron microscopy and X-ray diffraction techniques. 903 7

In insulin-dependent (Type 1) diabetes mellitus (IDDM) the development of nephropathy is partly due to genetic susceptibility. Previously one study has demonstrated a relationship between a HindIII restriction polymorphism of the collagen IV alpha 1-chain gene and diabetic nephropathy. The aim of the present study was to evaluate such as association in a case-control study including 207 Danish IDDM patients: 116 with nephropathy (urinary albumin excretion rate (AER) > 300 mg 24 h-1) and 91 without nephropathy (AER < 30 mg 24 h-1). Using genomic DNA, HindIII restriction fragment length analysis revealed a bi allele polymorphism visualized by southern hybridization with a cDNA probe recognizing the collagen IV alpha 1-chain gene. No differences in genotype frequencies or allele frequencies were demonstrated comparing patients with and without nephropathy: p = 0.39 and p = 0.96, respectively. Neither were there any difference in genotype frequencies or allele frequencies when the patients were stratified according to the presence of proliferative retinopathy: p = 0.44 and p = 0.84, respectively. Pooling the diabetic groups revealed genotype frequencies and allele frequencies comparable to those found in 57 healthy unrelated Danish individuals. We conclude that in a Danish IDDM population a HindIII restriction polymorphism of the collagen IV alpha 1-chain gene is not associated with diabetic nephropathy, diabetic retinopathy or with diabetes per se.
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PMID:Genetic variation of a collagen IV alpha 1-chain gene polymorphism in Danish insulin-dependent diabetes mellitus (IDDM) patients: lack of association to nephropathy and proliferative retinopathy. 904 92

To characterize the molecular mechanism of cardiac and renal complications in non-insulin-dependent diabetes mellitus (NIDDM), we examined the gene expression of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a new animal model for human NIDDM, at the ages of 14 weeks (prediabetic stage), 30 weeks (NIDDM stage), and 54 weeks (IDDM stage). Tissue mRNA levels were measured by Northern blot analysis. In 14-week-old OLETF rats, cardiac mRNAs for transforming growth factor-beta1 (TGF-beta1) and extracellular matrix, including collagen types I, III, and IV and laminin, were significantly increased compared with control rats (Long-Evans Tokushima Otsuka rats). Cardiac beta-myosin heavy chain (MHC) mRNA of OLETF was increased at 30 and 54 weeks of age, whereas alpha-MHC mRNA of OLETF was inversely decreased at 54 weeks. Marked perivascular fibrosis was seen in the hearts of OLETF rats from 30 weeks of age. In the kidney of OLETF rats, glomerular TGF-beta1 expression was temporally increased at 30 weeks of age, followed by glomerulosclerosis characterized by mesangial proliferation, thickening of the basement membrane, and nodular lesions. Blood pressure of OLETF rats remained higher than that of control rats from the prediabetic stage to the IDDM stage. Thus, in OLETF rats, cardiac fibrosis-related gene expressions were already enhanced at the prediabetic stage, which supports the involvement of these gene expressions in cardiac perivascular fibrosis. The antithetical change in beta- and alpha-MHC expressions seems to participate in the decreased cardiac contractility seen in diabetes. Furthermore, TGF-beta1 may also contribute to glomerulosclerosis of OLETF rats. OLETF rats seem to be a useful model to study the mechanism of hypertension and cardiac and renal complications in NIDDM.
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PMID:Characteristics of diabetes, blood pressure, and cardiac and renal complications in Otsuka Long-Evans Tokushima Fatty rats. 905 88


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