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)

Diabetes, with only mild ketosis, was induced in male rats by a single injection of streptozotocin. After 12 weeks the specific activities of enzymes concerned with the metabolism of inositol and of inositol lipids were measured in various tissues. Inositol 1-phosphate synthase (EC 5.5.1.4) was most active in testis and the activity was significantly less in diabetic rats than in controls on a similar diet. Inositol oxygenase (EC 1.13.99.1), which converts myo-inositol into glucuronic acid, was also less active in kidney from diabetic animals. CDP-diacylglycerol-inositol phosphatidyltransferase (EC 2.7.8.11) and phosphatidylinositol 4-phosphate kinase (EC 2.7.1.68) showed decreased specific activities in brain and sciatic nerve of diabetic rats. By contrast the diabetic state did not affect the specific activities of phosphatidylinositol kinase (EC 2.7.1.67) or phosphatidylinositol 4,5-bisphosphate phosphatase (EC 3.1.3.36) in these tissues. The results are discussed in relation to diabetic neuropathy.
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PMID:Enzymes of myo-inositol and inositol lipid metabolism in rats with streptozotocin-induced diabetes. 22 62

The clinical role of insulin-antibody formation, with reference to the monocomponent insulin treatment (MC), is discussed in a series of diabetological conditions. On the basis of a five-year-experience, personal results with a MC Lente treatment are presented in 32 cases of juvenile diabetes subdivided as follows: 3 cases with insulin allergy, 5 cases with insulin lipoatrophy, 13 cases with high insulin requirement, 4 cases with brittle diabetes, 7 cases with diabetic microangiopathy (retinal and, or renal). The circulating antibody level was estimated by IgG-Insulin-Binding Capacity (IB), according to Christiansen. After transfer from conventional to MC insulin treatment it was observed: -- disappearance of allergy and total remission of lipoatrophy, in parallel with a reduction of IB titer; -- decrease in insulin requirement and stabilisation of labile diabetic control, not always in concomitance with IB reduction; -- deterioration of advanced diabetic retinopathy and, or nephropathy in spite of IB reduction. It is concluded that MC insulin constitutes a major tool in the treatment of the above mentioned diabetic conditions, except for advanced microangiopathy. Thus a MC insulin treatment should be started, as a rule, in newly diagnosed diabetics, to possibly prevent such complications. However further development of insulin purification techniques, with removal of residual pro-insulin antigenic sites, is to be considered.
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PMID:[Long-term clinical results with monocomponent insulin (MC lente) in infantile and juvenile diabetes]. 102 49

Amniotic fluid (AF) creatinine concentrations, determined in 353 samples from 167 pregnancies complicated by maternal diabetes, are similar to those found at comparable gestation in uncomplicated pregnancy. Added maternal vascular disease significantly raises AF creatinine to such a degree that overestimation of fetal (renal) maturity is a clinical hazard if based solely on this parameter. Relative concentrations of creatinine in AF and maternal plasma (AF/MP ratio) are related to gestational age. Failure of AF creatinine to rise consistently on successive serial samples accompanies an increased risk of perinatal death in the pregnancy complicated by diabetes, four of five deaths in the present series following declines in this measurement.
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PMID:Amniotic fluid creatinine in pregnancies complicated by diabetes. 113 Apr 43

In the malformation analysis of 445 patients ascertained only for a sacrococcygeal malformation, a new phenotype, the sacrococcygeal dysgenesis association (SDA), was delineated in 34%. In addition, sirenomelia patients were found in 12%, the VATER association in 27%, and 27% could not be classified. Heterogeneity in the patients with sacrococcygeal malformations was identified by the differences found in their associated malformations. SDA patients have a relatively small average number (3.3) of anomalies per patient as compared with 9.3 in sirenomelia and 6.2 in VATER patients. SDA abnormalities occurred to a significant degree only in 6 of 20 designated malformation categories (vertebral, rib, pelvic, lower limb, central nervous system [CNS], renal) in contrast to 17 in VATER and 18 in sirenomelia patients. The SDA vertebral malformation pattern also differed from that of VATER/sirenomelia patients as did the high sacrococcygeal agenesis:dysgenesis ratio and low thoracolumbar vertebrae and/or rib hypersegmentations. Most significantly, SDA patients had a large number of CNS anomalies and CNS-related dysfunctions of the urinary and distal intestinal tracts but no anatomic urinary or intestinal tract malformations. This contrasted sharply with the markedly increased occurrences of anatomic abnormalities in these body regions of the sirenomelia and VATER patients. Demographic data such as patient survival, twinning and, particularly, the high (28%) incidence of maternal diabetes in the SDA further support its differentiation from VATER/sirenomelia patients.
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PMID:Sacrococcygeal dysgenesis association. 178 25

Hyperglycemic diabetics are prone to unusual or especially severe infections; at the cellular level, diabetic polymorphonuclear leukocytes (PMNs) show defects in several antimicrobial functions. However, the basis for these defects is unknown, and they may not be fully ascribable to hyperglycemia, hypoinsulinemia or acidosis alone. Recently, it has been shown that several important PMN functions may be mediated (at least in part) by metabolites of arachidonic acid synthesized via the lipoxygenase pathway, especially arachidonate hydroperoxides and leukotriene (LT) B4. We speculate that synthesis of these mediators may be deficient in severely hyperglycemic diabetics (fasting plasma glucose greater than 250-300 mg/dl) due to deficiencies of substrate (arachidonic acid) synthesis and release. Such defects might be expected since, in animal studies, severe insulin lack and glucagon excess inhibit the desaturation of precursor fatty acids to arachidonic acid. On the other hand, whereas low levels of lipid peroxides or their derivatives may be required in certain cells for normal function, excessive levels of such compounds also are detrimental to cellular function and could play a role as well in the complications of milder or partially treated diabetics who manifest high basal insulin levels. For example, cells which may be particularly sensitive to an excess of peroxides include islet beta cells, PMNs and possibly vascular endothelial cells (all of which appear to be deficient in glutathione peroxidase). These observations suggest a role for accumulation of lipid peroxides in the impaired insulin secretion, defective PMN function and possibly endothelial death and increased vascular (retinal, endothelial, and renal) permeability of some milder diabetics. The available data are compatible with the speculation that in partially treated or lesser degrees of hyperglycemia, increased arachidonate synthesis and excessive lipid peroxidation may be present. Although it remains to be established that all of the results from experimentally-induced diabetics can be extrapolated to humans, these findings suggest that the cell damage attendant upon peroxide generation might be susceptible to prophylactic treatment with anti-oxidants such as alpha-tocopherol or ascorbic acid. In the more severe or later stages of hyperglycemia, a deficiency of lipoxygenase-derived products may supervene; dietary modifications designed to increase essential fatty acid availability might present a unique ancillary therapeutic approach at this stage of diabetes.
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PMID:Altered arachidonic acid synthesis and lipid peroxidation in diabetes mellitus: possible roles in leukocyte dysfunction and other cellular defects. 642 13

Numerous studies have shown that effective control of elevated blood pressure has greatly reduced the risk of stroke and, to a lesser extent, the risk of coronary artery disease. Although the relationship between diastolic blood pressure and both stroke and coronary disease is significant, systolic blood pressure correlates more strongly with stroke, congestive heart failure, coronary artery disease, declining renal function, and left ventricular hypertrophy. Studies have also shown that the presence of a wide pulse pressure (>/=60-70 mm Hg) also has an independent and major impact on coronary disease mortality and is strongly correlated with increased risk for cardiovascular disease. Because many hypertensives have end-organ damage (cardiac, central nervous system, renal), and the majority also have a comorbid condition such as diabetes and hyperlipidemia, which also increases cardiovascular risk, it is necessary to view the risks and comorbidity of hypertension and antihypertensive therapy in light of these problems. Despite evidence that antihypertensive therapy reduces the risk of stroke and coronary events, and despite the availability of effective agents, roughly half of the hypertensives in the United States remain untreated and only 24% have blood pressure <140 mm Hg systolic and 90 mm Hg diastolic. To ensure that hypertensive patients receive adequate therapy, physicians should treat patients aggressively and appropriately, avoiding antihypertensive drugs that adversely affect comorbid conditions and selecting those that also exert favorable therapeutic effects on these conditions.
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PMID:Blood pressure control. 890 Mar 37

Tacrolimus (FK 506) has been evaluated as immunosuppressive therapy in patients with a variety of solid organ and other transplants. Extensive data have now confirmed its efficacy as primary or rescue therapy in renal and hepatic transplantation. In prospective and historically controlled studies of primary therapy, tacrolimus generally demonstrated greater efficacy than the conventional formulation of cyclosporin for preventing episodes of acute rejection and allowed reduction of corticosteroid use. Chronic rejection rates were also significantly lower with tacrolimus in a large randomised liver transplantation trial. However, patient and graft survival rates were similar in both treatment groups (although numerically larger in adults with liver transplants). In children, rejection rates and corticosteroid requirements were usually lower with tacrolimus and patient and graft survival were generally similar with the 2 immunosuppressants. The finding of reduced corticosteroid requirements with tacrolimus may be of particular benefit in prepubertal children, who are still growing. A small amount of evidence has also accumulated regarding the use of tacrolimus as primary therapy in patients who have undergone bone marrow or heart and/or lung transplantation. Data are not conclusive, particularly in children, but tacrolimus appears to be useful for treating patients who have undergone these organ transplantations and may be associated with a lower incidence of obliterative bronchiolitis than cyclosporin in the latter group. Potential efficacy has also been shown in a limited number of patients with pancreas or pancreas-kidney, pancreatic islet and intestinal or multivisceral transplants, and in children who have undergone heart or heart-lung transplantation. Tacrolimus also has a use as rescue therapy in bone marrow, heart, lung and pancreatic transplantation, but data are currently insufficient for conclusions to be made. However, these results support the need for further study in these populations. Adverse effects occurring during tacrolimus therapy are generally of the type common to all immunosuppressive regimens. However, diabetes mellitus, neurotoxicity and nephrotoxicity are more common in tacrolimus than cyclosporin recipients. Hyperlipidaemia, hypertension, hirsutism and gingival hyperplasia are more common with cyclosporin. In 2 large multicentre clinical trials (US liver and European renal), tacrolimus was discontinued more frequently during the first year because of adverse events. However, the tolerability of tacrolimus appears related to dosage, improving as the dose is reduced. Tacrolimus should be considered an effective primary immunosuppressant in renal and hepatic transplantation. The drug is also a useful agent for rescue therapy in patients experiencing rejection or poor tolerability to cyclosporin. Thus, tacrolimus provides the clinician with an effective option for patients requiring immunosuppression and, with a different tolerability and efficacy profile to cyclosporin, it will better allow the tailoring of therapy to meet the needs of individual patients.
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PMID:Tacrolimus. An update of its pharmacology and clinical efficacy in the management of organ transplantation. 942 97

Impaired glucose tolerance (IGT) is a state in which there is postprandial hyperglycemia (> 7.8 mmol/L, or 140 mg/dL) with minimal elevations of fasting plasma glucose (> 5.5 < 7.8 mmol/L, > 100 < 140 mg/dL). This condition generally precedes the development of diabetes mellitus (DM) by several years. However, in IGT many of the metabolic abnormalities of DM are already present and provide insight into the pathogenesis of DM. Impaired early insulin release is the most consistent defect almost universally observed. Insulin resistance, attributable mainly to obesity, decreased physical fitness, or glucose toxicity, is also often present. The main reason that postprandial hyperglycemia occurs in IGT is impaired suppression of endogenous (hepatic and renal) glucose release; this can be largely explained by impaired early insulin release and impaired suppression of glucagon release. Postprandial glucose disposal is normal or increased, the result of hyperglycemia and delayed hyperinsulinemia. Postabsorptive (fasting) rates of glucose release and disposal and circulating levels of free fatty acids, glycerol, ketone bodies, lactate, and alanine are generally normal.
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PMID:Metabolic abnormalities in impaired glucose tolerance. 943 58

The present studies were undertaken to determine whether people with type 2 diabetes are resistant to the effects of glucose as well as insulin. Diabetic and nondiabetic subjects were studied on three occasions. Hormone secretion was inhibited with somatostatin. Insulin concentrations were kept at "basal" levels (referred to as low insulin infusion) from 0 to 180 min then increased to approximately 200 pmol/l from 181 to 360 min (referred to as high insulin infusion). Glucose concentrations were clamped at either approximately 95, approximately 130, or approximately 165 mg/dl on each occasion. In the presence of basal insulin concentrations, a progressive increase in glucose from 95 to 130 to 165 mg/dl was accompanied by a comparable and progressive decrease (P = 0.001 to 0.003 by analysis of variance [ANOVA]) in endogenous glucose production (measured with [6-(3)H]glucose) and total glucose output (measured with [2-(3)H]glucose) and incorporation of 14CO2 into glucose (an index of gluconeogenesis) in both diabetic and nondiabetic subjects, indicating normal hepatic (and perhaps renal) response to glucose. In the nondiabetic subjects, an increase in glucose concentration from 95 to 130 to 165 mg/dl resulted in a progressive increase in glucose disappearance during both the low (19.9 +/- 1.8 to 23.6 +/- 1.8 to 25.4 +/- 1.6 micromol x kg(-1) x min(-1); P = 0.003 by ANOVA) and high (36.4 +/- 3.1 to 47.6 +/- 4.5 to 61.1 +/- 7.0 micromol x kg(-1) x min(-1); P = 0.001 by ANOVA) insulin infusions. In contrast, in the diabetic subjects, whereas an increase in glucose from 95 to 130 mg/dl resulted in an increase in glucose disappearance during both the low (P = 0.001) and high (P = 0.01) dose insulin infusions, a further increase in glucose concentration to 165 mg/dl had no further effect (P = 0.41 and 0.38) on disappearance at either insulin dose (low: 14.2 +/- 0.8 to 18.2 +/- 1.1 to 18.7 +/- 2.4 micromol x kg(-1) x min(-1); high: 21.0 +/- 3.2 to 33.9 +/- 6.4 to 32.5 +/- 8.0 micromol x kg(-1) x min(-1) for 95, 130, and 165 mg/dl, respectively). We conclude that whereas glucose-induced stimulation of its own uptake is abnormal in type 2 diabetes, glucose-induced suppression of endogenous glucose production and output is not. The abnormality in uptake occurs in the presence of both basal and high insulin concentrations and is evident at glucose concentrations above but not below 130 mg/dl, implying a defect in a glucose-responsive step.
Diabetes 1998 Nov
PMID:Normal glucose-induced suppression of glucose production but impaired stimulation of glucose disposal in type 2 diabetes: evidence for a concentration-dependent defect in uptake. 979 43

Aldose reductase (ALR2), a NADPH-dependent aldo-keto reductase (AKR), is widely distributed in mammalian tissues and has been implicated in complications of diabetes, including diabetic nephropathy. To identify a renal-specific reductase belonging to the AKR family, representational difference analyses of cDNA from diabetic mouse kidney were performed. A full-length cDNA with an ORF of 855 nt and yielding a approximately 1.5-kb mRNA transcript was isolated from a mouse kidney library. Human and rat homologues also were isolated, and they had approximately 91% and approximately 97% amino acid identity with mouse protein. In vitro translation of the cDNA yielded a protein product of approximately 33 kDa. Northern and Western blot analyses, using the cDNA and antirecombinant protein antibody, revealed its expression exclusively confined to the kidney. Like ALR2, the expression was up-regulated in diabetic kidneys. Its mRNA and protein expression was restricted to renal proximal tubules. The gene neither codistributed with Tamm-Horsfall protein nor aquaporin-2. The deduced protein sequence revealed an AKR-3 motif located near the N terminus, unlike the other AKR family members where it is confined to the C terminus. Fluorescence quenching and reactive blue agarose chromatography studies revealed that it binds to NADPH with high affinity (K(dNADPH) = 66.9 +/- 2.3 nM). This binding domain is a tetrapeptide (Met-Ala-Lys-Ser) located within the AKR-3 motif that is similar to the other AKR members. The identified protein is designated as RSOR because it is renal-specific with properties of an oxido-reductase, and like ALR2 it may be relevant in the renal complications of diabetes mellitus.
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PMID:Identification of a renal-specific oxido-reductase in newborn diabetic mice. 1094 87


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