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)

Advanced glycosylation end products of proteins (AGEs) are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. A approximately 35-kDa polypeptide with a unique NH2-terminal sequence has been isolated from bovine lung and found to be present on the surface of endothelial cells where it mediates the binding of AGEs (receptor for advanced glycosylation end product or RAGE). Using an oligonucleotide probe based on the amino-terminal sequence of RAGE, an apparently full-length cDNA of 1.5 kilobases was isolated from a bovine lung cDNA library. This cDNA encoded a 394 amino acid mature protein comprised of the following putative domains: an extracellular domain of 332 amino acids, a single hydrophobic membrane spanning domain of 19 amino acids, and a carboxyl-terminal domain of 43 amino acids. A partial clone encoding the human counterpart of RAGE, isolated from a human lung library, was found to be approximately 90% homologous to the bovine molecule. Based on computer analysis of the amino acid sequence of RAGE and comparison with databases, RAGE is a new member of the immunoglobulin superfamily of cell surface molecules and shares significant homology with MUC 18, NCAM, and the cytoplasmic domain of CD20. Expression of the RAGE cDNA in 293 cells allowed them to bind 125I-AGE-albumin in a saturable and dose-dependent manner (Kd approximately 100 nM), blocked by antibody to RAGE. Western blots of 293 cells transfected with RAGE cDNA probed with anti-RAGE IgG demonstrated expression of immunoreactive protein compared to its absence in mock-transfected cells. These results suggest that RAGE functions as a cell surface receptor for AGEs, which could potentially mediate cellular effects of this class of glycosylated proteins.
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PMID:Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. 137 43

Sera from 17 patients with Type I diabetes and 19 healthy volunteers have been examined to evaluate whether the kinetics of the binding of drugs to Site II of serum albumin is altered in diabetes. Stopped-flow measurements showed that the association velocity and the affinity constants of the fluorescent marker dansylsarcosine were significantly lower in diabetes (160 s-1 and 2.0 x 10(5) l.mol-1) than in non-diabetics (196 s-1 and 4.0 x 10(5) l.mol-1). The dissociation velocity was not different [20.3 s-1 vs. 19.4 s-1]. Although patients with a reduced albumin concentration were excluded the diabetics had significantly lower concentrations than the healthy volunteers. There was a significant correlation between decreased glycosylation of albumin and increased association velocity. The dissociation velocity constants were correlated with the molar concentration ratio of free fatty acids/human serum albumin. Thus, the extent of glycosylation and the amount of fatty acids bound per mole albumin can both affect the kinetics of drug binding to Site II. The lower affinity in patients with Type I diabetes is due to the increased in the glycoalbumin concentration.
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PMID:Drug-protein binding kinetics in patients with type I diabetes. 138 Apr 61

We studied the effects of salt loading on glucose tolerance, blood pressure, and albuminuria in rats with mild non-insulin-dependent diabetes mellitus (NIDDM). Two-day-old male Wistar Kyoto (WKY) rats were injected intraperitoneally (IP) with either 75.0 mg/kg streptozotocin (STZ) or vehicle as control. Salt loading was performed as 1% NaCl of drinking solution from 4 weeks until 12 weeks of age (estimated sodium intake: control, 3.14 +/- 0.28 mEq/d in tap-water group, 11.9 +/- 0.95 mEq/d in salt-loaded group; NIDDM, 2.93 +/- 0.16 mEq/d in tap-water group, 12.0 +/- 2.59 mEq/d in salt-loaded group). Oral glucose tolerance, glycosylated hemoglobin (GHb), and pancreatic insulin content at 12 weeks did not differ between the salt-loaded group and tap-water group in both NIDDM and control rats. Urinary sodium excretion was increased in salt-loaded groups of control and NIDDM rats, but systolic blood pressure did not differ among the groups (control, 151 +/- 6 mm Hg in tap-water group, 150 +/- 3 mm Hg in salt-loaded group; NIDDM, 152 +/- 3 mm Hg in tap-water group, 157 +/- 2 mm Hg in salt-loaded group). Urinary albumin excretion was significantly increased in salt-loaded groups (1,790 +/- 272 micrograms/d in control, 1,617 +/- 174 micrograms/d in NIDDM rats) compared with tap-water groups (691 +/- 75 micrograms/d in control, P less than .05; 616 +/- 69 micrograms/d in NIDDM rats, P less than .001), irrespective of STZ injection, but endogenous creatinine clearance was not different among the groups. Furthermore, renal growth was more greatly increased in salt-loaded groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of salt loading on glucose tolerance, blood pressure, and albuminuria in rats with non-insulin-dependent diabetes mellitus. 138 98

1. It has been suggested that hypertension may be an important determinant of the rate of progression of diabetic microangiopathy. 2. Renal microvascular disease as assessed by urinary albumin excretion and glomerular ultrastructure was evaluated in a model in which streptozotocin diabetes was induced in spontaneously hypertensive rats (SHR). 3. Diabetes was associated with increases in urinary albumin excretion, and hypertension resulted in a further increase in albuminuria. 4. Various antihypertensive regimens were administered to diabetic SHR, with the angiotensin-converting enzyme inhibitor perindopril and triple therapy (hydralazine, reserpine and hydrochlorothiazide) being more effective than the calcium antagonist (lacidipine) in retarding the increase in albuminuria in diabetic SHR. 5. Antihypertensive therapy appears to ameliorate the development of diabetic renal disease.
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PMID:Diabetic renal microvascular disease: the role of hypertension and ACE inhibitors. 139 13

A working group was established in order to suggest the process and outcome variables most appropriate for the continuing audit of diabetes services. The proposed audit is being piloted in hospitals in selected United Kingdom Health Districts. The main process and outcome measures suggested are: waiting and consultation times; missed or cancelled appointments; information given to patients and the primary care team; knowledge of diabetes and risks of smoking; recording of key examinations and investigations, i.e. levels of glycosylated haemoglobin (or equivalent), serum cholesterol, body mass index, blood pressure, albumin excretion rate, presence and extent of retinopathy, history of coronary artery, cerebrovascular or peripheral vascular disease; history of severe hypoglycaemia; presence of foot problems; psychological well-being; patient satisfaction; admission rates and hospital bed days for hyperglycaemic and other diabetes related emergencies.
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PMID:A proposal for continuing audit of diabetes services. Home and Members of a Working Group of the Research Unit of the Royal College of Physicians and British Diabetic Association. 848 66

The effects of glycation of either albumin, a plasma protein, or GBM were examined in an in vitro model of GBM permeability. Albumin was incubated with glucose in vitro, and nonglycated and glycated albumin were separated by affinity chromatography. Rat GBM was glycated either in vivo after the induction of diabetes or in vitro after incubation with 25 mM glucose. 150 micrograms of GBM was consolidated in an ultrafiltration cell, and albumin permeability across the GBM filter was assessed at an applied pressure (50 mmHg) selected to approximate glomerular capillary pressure in vivo. The sieving coefficient of glycated albumin was greater than the sieving coefficient of nonglycated albumin (0.25 +/- 0.03 vs. 0.10 +/- 0.02; P < 0.05). GBM glycated in vivo in diabetic rats exhibited native albumin and water permeability that was indistinguishable from that for GBM from control rats. Similarly, GBM glycated in vitro by incubation with 25 mM glucose exhibited water and albumin permeability identical to that for GBM incubated in buffer. Thus, the glycation of albumin, but not of GBM, leads to enhanced permeability in an in vitro GBM filtration system. Increased permeability of glycated albumin may contribute to albuminuria and/or renal injury in states of increased circulating glycated albumin such as diabetes and experimental galactosemia.
Diabetes 1992 Nov
PMID:Glycation of albumin, not glomerular basement membrane, alters permeability in an in vitro model. 139 17

The established correlation between diabetes and periodontal diseases and the increasing prevalence of Type II diabetes in the general population indicate that dental practitioners will probably treat an increasing number of diabetic patients. Despite the fact that there is little scientific evidence to support the concept, it has been generally accepted that treatment for periodontal disease in diabetic patients may reduce insulin requirements and improve metabolic balance. However, to date no one has evaluated the effects of periodontal therapy on the metabolic state of the poorly-controlled diabetic patient. The purpose of this pilot study was to evaluate the effect of controlling gingival inflammation on blood glucose levels as determined by glycosylation of hemoglobin and albumin.
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PMID:The relationship between reduction in periodontal inflammation and diabetes control: a report of 9 cases. 140 92

Glycated hemoglobin (GHb), fructosamine and glycated albumin (GA) in hemolytic sera from cadavers were analyzed for the postmortem diagnosis of diabetes mellitus. The levels of GHb and fructosamine were determined by boronate affinity chromatography and colorimetry, respectively. Albumin fraction was isolated from the samples by Affi-Gel Blue affinity chromatography. The glycated and non-glycated molecules were separated by boronate affinity chromatography, and quantitated by bromcresol green method. Fructosamine could not be analyzed from highly hemolytic sera containing more than 10 g/l hemoglobin. In such samples, the levels of GHb and GA were deviated from the standard values, indicating their postmortem degradation. In less hemolytic samples, GA was as informative as GHb and fructosamine for the diagnosis of diabetes mellitus.
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PMID:Analysis of glycated albumin in postmortem blood samples as the diagnostic parameters of diabetes mellitus. 140 16

Case mix and laboratory predictors of death risk were evaluated in 17,185 hemodialysis patients. The laboratory variables most closely associated with the increased death risk borne by diabetic patients (relative to non-diabetics) and White patients (relative to non-Whites) were identified. The analyses of laboratory death risk predictors were similar to those previously reported. Serum albumin concentration is the most powerful death risk predictor among all of the variables, both case mix and laboratory. Statistical models including only case mix variables reveal both race (RRWhites = 1.42) and diabetes (RRdiabetes = 1.43) as significant predictors. Adding creatinine, albumin, and BUN concentrations to the model eliminated diabetes as a significant predictor. Creatinine and albumin accounted for most of the change. Adding only creatinine eliminated race. The data suggest that reduced visceral and somatic protein mass and/or metabolism may be important determinants of mortality in dialysis patients. Because differences in the concentrations of creatinine and albumin explain much of the risk associated with being White or diabetic, differences in nutritional status may explain the reduced survival observed in those groups. Therefore, clinicians should not simply accept without question the notion that diabetics and Whites are doomed to inferior survival.
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PMID:Race and diabetes as death risk predictors in hemodialysis patients. 140 77

Diabetic nephropathy is a common complication in diabetes mellitus. In addition to the risk of renal failure, patients with established nephropathy are at increased risk of proliferative retinopathy and cardiovascular disease. As the earliest prodrome of nephropathy is microalbuminuria, albumin excretion needs to be monitored with a reliable method in all diabetics. In the event of microalbuminuria, diabetes treatment needs to be intensified to optimise metabolic regulation. Early institution of antihypertensive treatment is essential to avoid progression to clinical nephropathy.
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PMID:[Diabetic nephropathy]. 140 27


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