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)

The aim of this study was to assess bone status in 220 subjects with end-stage renal failure (ESRF) (146 men, mean age 53.0 +/- 13.9 years and 74 women, mean age 48.1 +/- 14.3 years). The duration of hemodialysis (durHD) and duration of renal insufficiency (durRI) were, in men, 2.6 +/- 3.8 years and 7.7 +/- 8.0 years, and, in women, 2.8 +/- 3.4 years and 9.1 +/- 7.6 years, respectively. ESRF was caused by the following reasons: chronic glomerulonephritis in 92 patients, diabetes in 52, chronic pyelonephritis in 37, polycystic kidney disease in 19, amyloidosis in 5, hypertension in 4 and unknown cause in 11. The control group consisted of 1615 normal healthy subjects (1216 women, mean age 48.1 +/- 12.1 years and 399 men, mean age 52.9 +/- 14.8 years). Mean age did not differ between patients and controls. Skeletal status was evaluated by quantitative ultrasound (US) measurements at the hand phalanges using DBM 1200 (IGEA, Italy) which measures amplitude-dependent speed of sound (Ad-SoS, m/s). The mean value of Ad-SoS in male patients was 1981 +/- 88 m/s, T-score -l2.03 +/- 1.26, Z-score -0.53 +/- 1.7 and, in female patients, 1967 +/- 96 m/s, -2.23 +/- 1.37, -1.41 +/- 1.56, respectively. Respective values in male controls were 2008 +/- 81 m/s, -1.66 +/- 1.16, -0.01 +/- 0.98 and, in female controls, 2026 +/- 81 m/s, -1.4 +/- 1.15, -0.74 +/- 0.86, and were significantly higher than in male (p < 0.001) and female (p < 0.0000001) patients. A correlation analysis of Ad-SoS with durHD and durRI showed that only in males did both factors significantly influence parameters measured (r = -0.26, p < 0.01). Multiple stepwise regression analysis of Ad-SoS on age, durHD, durRI, weight and height was possible to perform only in males and the following equation was established: Ad-SoS = 2545 m/s - 3.09 x age (years) - 5.68 x durHD (years) - 2.15 x height (cm) - 0.99 x durRI (years), p < 0.000001, r = 0.55, SEE = 69.6. Concluding, in subjects with ESRF treated with hemodialysis, skeletal status assessed with the use of quantitative US was affected.
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PMID:Quantitative ultrasound at hand phalanges in adults with end-stage renal failure. 1512 Dec 47

The recent identification in Chlamydomonas of the intraflagellar transport machinery that assembles cilia and flagella has triggered a renaissance of interest in these organelles that transcends studies on their well-characterized ability to move. New studies on several fronts have revealed that the machinery for flagellar assembly/disassembly is regulated by homologs of mitotic proteins, that cilia play essential roles in sensory transduction, and that mutations in cilia/basal body proteins are responsible for cilia-related human disorders from polycystic kidney disease to a syndrome associated with obesity, hypertension, and diabetes.
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PMID:Cilia and flagella revealed: from flagellar assembly in Chlamydomonas to human obesity disorders. 1518 71

Incubation of rat pancreatic islets for 4-6 h with 100 micromol/l fatty acid-free BSA induced a 3- to 10-fold enhancement of insulin release to a subsequent challenge with 16.7 mmol/l glucose, without changing the typical biphasic pattern of the response. A similar enhancement was observed with other stimuli, such as leucine, depolarizing concentrations of KCl and tolbutamide, pointing to a general phenomenon and common mechanism for the augmentation. Norepinephrine completely blocked the stimulated response. The protein kinase C (PKC) inhibitor Ro 31-8220, which acts at the ATP-binding site and inhibits all PKC isoforms, strongly inhibited the enhancement of a subsequent glucose challenge when present during the BSA pretreatment period. In contrast, Go 6976, an inhibitor of conventional PKC isoforms, was without effect, even at the high concentration of 1 micromol/l. Preincubation with calphostin C, which competes for the diacylglycerol (DAG)-binding site, therefore inhibiting conventional, novel, and PKC isoforms of the PKD type, completely abolished the enhancing effect of the BSA but did not affect secretion in islets treated with 10 micromol/l fatty acid-free BSA. We conclude that the remarkable enhancement of insulin release is due to a change in glucose signaling and activation of a novel PKC isoform or a DAG-binding protein.
Diabetes 2004 Dec
PMID:Massive augmentation of stimulated insulin secretion induced by fatty acid-free BSA in rat pancreatic islets. 1556 45

Biologists have long known that humans experience their environment through cilia. Light, odorant, and sound perception depend on these microtubule-filled, complex organelles present on cells in primary sensory tissues. Recently, discoveries on the mechanism of assembly of cilia (flagella) in the lowly, biflagellated, eucaryotic green alga Chlamydomonas have triggered a renaissance of interest in the organelles along with a recognition of their key sensory roles in nonsensory tissues. Chlamydomonas researchers uncovered an entirely new set of cellular machinery essential for transporting the protein components of cilia and flagella in all ciliated/flagellated eukaryotic cells between their site of synthesis in the cell body and their site of assembly at the tip of the flagellum (intraflagellar transport: IFT). Prompted by the surprising observations that disruption of IFT genes in mice led to polycystic kidney disease (PKD) and that PKD proteins are present on the sensory cilia of Caenorhabditis elegans, researchers have made a direct connection between PKD and cilia. At least five (and possibly all) of the seven identified human genes disrupted in PKD and a related disorder nephronophthisis encode proteins expressed in the primary cilia that project into the lumen from the epithelial cells that line renal tubules. Moreover, the renal cilia are flow sensors and at least two of the PKD genes encode ciliary transmembrane proteins essential for mechanosensation. Although their roles have not yet been as clearly identified, cilia also are at the center of a rare human disorder, Bardet-Biedl syndrome (BBS), in which patients exhibit phenotypes of common human diseases, including obesity and increased incidence of hypertension and diabetes. Five of the eight known BBS genes encode basal body or cilia proteins in mice or humans, and homologues of two of the remaining genes are present in basal bodies/cilia of model organisms. Here we briefly describe the biology of cilia and flagella, we outline how studies on model organisms have led to our current understanding of the roles of these organelles and their proteins in health and disease, and we highlight the notion that the primary cilia present on cells throughout the body, even those on brain neurons, may be essential for as yet undiscovered cilium-generated signaling functions.
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PMID:Cilium-generated signaling and cilia-related disorders. 1572 88

Nitric oxide (NO) is thought to be an important factor in the deterioration of renal function. A variable-number tandem 27-bp repeat in intron 4 of the endothelial cell nitric oxide synthase (NOS3) gene has been found to be associated with the plasma levels of NO metabolites. Two alleles are of varied frequencies in different populations (a and b). The shorter allele a has been associated in Japanese populations with the progression of renal disease. Here we investigated this hypothesis by studying the putative role of this polymorphism in a Hellenic population of patients with end-stage renal disease (ESRD). We analyzed the genotypes of 361 ESRD patients and 295 healthy Hellens from Greece and Cyprus. The frequencies of NOS3-4bb, NOS3-4ab, and NOS3-4aa were 0.69, 0.27, and 0.03, respectively, in the control group and 0.71, 0.24, and 0.04 in the group of patients. The data in the two populations were analyzed by the chi-square and Fisher's exact tests. The frequencies of these three genotypes of NOS3-4 polymorphism in the Hellenic population of Greece and Cyprus are similar to those observed in other Caucasian populations. Moreover, our results from three patient groups, autosomal dominant polycystic kidney disease (ADPKD), diabetes mellitus (DM), and non-DM, showed that the frequencies of aa and ab genotypes in the patient populations were not significantly different from those observed in the control group. This work indicates that NOS3-4 polymorphism does not show any association with the development of ESRD in this studied European population. However, examination of the data regarding progression to ESRD within 5 years or after more than 5 years following clinical diagnosis of ADPKD provided evidence of statistical difference (p = 0.048, before Bonferroni correction), with faster progression in the group of ADPKD patients who carried allele a.
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PMID:Evidence for association of endothelial cell nitric oxide synthase gene polymorphism with earlier progression to end-stage renal disease in a cohort of Hellens from Greece and Cyprus. 1572 57

In a retrospective study we examined the differences between Caucasian (Group A) and Gypsy (Group B) renal allograft recipients transplanted in Hungary. From 1983 to 2001, 1918 transplants were performed in Budapest (1825 Caucasian and 93 Gypsy recipients). Group B patients were younger (34 +/- 12 vs 42 +/- 14 years of age; P < .01) and Group A had more polycystic kidney disease (12% vs 3%; P < .025). Blood group B was more common in Group B (27% vs 19%; P = NS) than in Group A patients, and Group A had seemingly more diabetes (5% vs 1%; P = NS) than did Group B. There were no differences in HLA mismatches or panel reactive antibodies (PRA). No differences were seen in Group A vs Group B patient survivals at 1, 3, 5, or 10 years' posttransplant (98% vs 95%; 90% vs 93%; 85% vs 88%; and 74% vs 82%, respectively). However, Group A graft survivals were significantly better than Group B at 1, 3, 5, and 10 years' posttransplant (89% vs 77%; 82% vs 66%; 76% vs 54%; and 57% vs 34%; each comparison P < .01). Group B recipients experienced a greater number of acute rejection episodes (66% vs 49%; P < .01), irreversible acute rejections (15% vs 6%; P < .001), chronic rejections (34% vs 18%; P < .001), and graft loss due to immunosuppression noncompliance (5% vs 1%; P < .05) than did Group A recipients. As has been previously described for other non-Caucasian ethnic groups (eg, African-Americans), Hungarian Gypsies appear to be at a greater immunological risk for rejection and poorer long-term graft survival.
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PMID:Significant differences in the efficacy of kidney transplantation between Hungarian Caucasians and Gypsies. 1584 15

Hepatocyte nuclear factor-1beta (HNF-1beta) is a Pit-1/Oct-1/Unc-86 (POU)/homeodomain-containing transcription factor that regulates tissue-specific gene expression in the kidney, liver, pancreas, and other epithelial organs. Mutations of HNF-1beta produce maturity-onset diabetes of the young type 5 (MODY5) and are associated with congenital cystic abnormalities of the kidney. Transgenic mice expressing mutant HNF-1beta under the control of a kidney-specific promoter develop kidney cysts and renal failure, which is similar to the phenotype of humans with MODY5. Similarly, kidney-specific deletion of HNF-1beta using Cre/loxP recombination results in renal cyst formation. HNF-1beta directly regulates the Pkhd1 promoter. HNF-1beta mutant mice show decreased expression of Pkhd1, the gene that is mutated in humans with autosomal-recessive polycystic kidney disease (ARPKD). These studies demonstrate that HNF-1beta is required for the development of the mammalian kidney. They establish a previously unrecognized link between two renal cystic diseases, MODY5 and ARPKD, and suggest that the mechanism of cyst formation in humans with mutations of HNF-1beta involves down-regulation of PKHD1 gene transcription.
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PMID:Roles of HNF-1beta in kidney development and congenital cystic diseases. 1622 Nov 71

The short-chain oxidoreductase (SCOR) family of enzymes includes over 6,000 members identified in sequenced genomes. Of these enzymes, approximately 300 have been characterized functionally, and the three-dimensional crystal structures of approximately 40 have been reported. Since some SCOR enzymes are steroid dehydrogenases involved in hypertension, diabetes, breast cancer, and polycystic kidney disease, it is important to characterize the other members of the family for which the biological functions are currently unknown and to determine their three-dimensional structure and mechanism of action. Although the SCOR family appears to have only a single fully conserved residue, it was possible, using bioinformatics methods, to determine characteristic fingerprints composed of 30-40 residues that are conserved at the 70% or greater level in SCOR subgroups. These fingerprints permit reliable prediction of several important structure-function features including cofactor preference, catalytic residues, and substrate specificity. Human type 1 3beta-hydroxysteroid dehydrogenase isomerase (3beta-HSDI) has 30% sequence identity with a human UDP galactose 4-epimerase (UDPGE), a SCOR family enzyme for which an X-ray structure has been reported. Both UDPGE and 3-HSDI appear to trace their origins back to bacterial 3alpha,20beta-HSD. Combining three-dimensional structural information and sequence data on the 3alpha,20beta-HSD, UDPGE, and 3beta-HSDI subfamilies with mutational analysis, we were able to identify the residues critical to the dehydrogenase function of 3-HSDI. We also identified the residues most probably responsible for the isomerase activity of 3beta-HSDI. We test our predictions by specific mutations based on sequence analysis and our structure-based model.
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PMID:Determining structure and function of steroid dehydrogenase enzymes by sequence analysis, homology modeling, and rational mutational analysis. 1646 63

In isolated liver transplantation pretransplant renal failure is a major mortality risk, there are no guidelines at the moment to establish the indications for a combined liver-kidney transplantation (LKT). In irreversible chronic renal failure (CRF) not on dialysis, nephrological evaluation is required to assess the need for a simultaneous kidney transplantation. There are no experiences about the functional contribution of native kidneys post-LKT. Herein we have reported the case of two patients who underwent LKT in 2004 due to CRF, not yet on dialysis. At the moment of LKT, the first patient (polycystic kidney disease) had a glomerular filtration rate (GFR) = 29 mL/min, and the second recipient (vascular nephropathy and diabetes), a GFR = 33 mL/min. In both cases we did not observe delayed graft function. At discharge the serum creatinine was 1.1 and 1.0 mg/dL, respectively, which was maintained during follow-up. In both cases renal scintigraphy with Tc-99 DMSA was performed to evaluate the functional contributions of transplanted versus native kidneys. In the first case scintigraphy at 9 months after LKT demonstrated an 81% contribution from the transplanted kidney, 9% from the right and 10% from the left native kidneys. In the second case, at 3 months after LKT, the functional contributions were 76%, 10%, and 14%, respectively. The transplanted kidney nephron mass may avoid the need for hemodialysis in the early posttransplant period; in the midterm it may help to maintain residual renal function. As in other combined transplant programs (heart-kidney, kidney-pancreas) with irreversible CRF, a GFR < or = 30 to 35 mL/min may be an indication for LKT, but we need more experience.
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PMID:Nephrological indications in combined liver-kidney transplantation. 1675 72

Recently, there has been extensive debate about extending the criteria for accepting living donors to include the presence of mild renal abnormalities such as isolated microhematuria. Hematuria defined as the detection of greater than five red blood cells per high power field can be associated with abnormalities throughout the urinary tract. Detection of casts or dysmorphic red blood cells in the urine sediment with or without proteinuria could indicate underlying intrinsic renal disease. Anatomic causes, such as stones and tumors, should be excluded; cystoscopy may be indicated to exclude bladder pathology. Obviously, urinary tract infection, uncontrolled hypertension and latent diabetes mellitus must be excluded. Microscopic hematuria could be associated with mesangial IgA deposits; as 10% of first-degree relatives of patients with IgA glomerulonephritis suffer from microhematuria and/or proteinuria that may require consideration of renal biopsy. Microhematuria could also be associated with other known hereditary renal diseases such as C3 deposits disease, IgM nephropathy, autosomal dominant polycystic kidney disease, Alport's syndrome or thin basement membrane disease. In conclusion, careful assessment of isolated microhematuria, in the context of living kidney donation, is mandatory as results may reveal occult renal disease that may contraindicate kidney donation.
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PMID:The renal allograft donor with isolated microhematuria. 1697 Feb 50


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