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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunotactoid glomerulopathy is characterized by the ultrastructural finding of fibrillary or microtubular deposits in patients without systemic diseases such as SLE, diabetes, paraproteinemias, cryoglobulinemia, or amyloidosis. These deposits correspond in most (but not all) cases to immunoglobulin and complement deposits as shown by immunohistochemical techniques. Different light microscopic patterns (mesangioproliferative, membranous, membranoproliferative, and crescentic) have been reported. Clinical presenting feature is characterized by proteinuria (often of nephrotic range), hematuria, and hypertension in most cases. Chronic renal failure requiring hemodialysis or transplantation is described in more than half the patients. Pathogenesis has not yet been elucidated and only some speculative hypotheses have so far been suggested. At present there is no clear evidence that we are dealing with a new pathologic entity, but larger series must be collected and studied in order to find a correct taxonomic collocation of this glomerulopathy.
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PMID:Immunotactoid glomerulopathy (ITGP): a not fully defined clinicopathologic entity. 851 98

Proliferation of mesangial cells is a feature of several forms of human and experimental glomerulopathy, including that seen in diabetes. The nonsulfated glycosaminoglycan hyaluronan participates in the regulation of pericellular matrix assembly and is a mitogen in some cell types. We have shown previously that hyaluronan production is increased in the glomerulus in a glucose- and prostaglandin-dependent manner. We have investigated the effect of diabetes and of addition of hyaluronan and prostaglandin E2 (PGE2) on the uptake of [3H]thymidine by glomerular core preparations enriched in mesangial cells. When compared with nondiabetic controls, it was shown that [3H]thymidine uptake was significantly increased in glomerular core preparations from streptozotocin-induced diabetic rats (to 169 +/- 5%, P < 0.001). In glomerular cores from both experimental groups, hyaluronan (50-250 ng/ml) or PGE2 (10(-12) to 10(-8) mol/l) increased the uptake of [3H]thymidine. Further, mesangial cells from nondiabetic control glomerular cores, when maintained in culture in early passage, responded with increased [3H]thymidine uptake to raised glucose (5.6-25 mmol/l) and to added hyaluronan and PGE2. We propose that prostaglandin and hyaluronan production in response to a raised glucose environment in diabetes can contribute to mesangial hypercellularity.
Diabetes 1996 Jan
PMID:Effect of prostaglandin E2 and hyaluronan on mesangial cell proliferation. A potential contribution to glomerular hypercellularity in diabetes. 852 58

The prevalence of hypertension in diabetes is significantly higher than in non-diabetics, perhaps twice as common. The excess is related to diabetic nephropathy, mainly in type 1 diabetes, to obesity, mainly in type 2 diabetes, but also to increased sympathetic activity. Furthermore, the increased prevalence of hypertension may relate to insulin resistance and its sequelae. Insulin resistance leads to hyperinsulinemia, relates to increased LDL and reduced HDL levels, causes the development of impaired glucose tolerance and type 2 diabetes and might also be causally related to the onset of hypertension. Syndrome X has relevant therapeutic implications in the management of hypertension. Hypertension is a major risk factor for large vessel disease in diabetics and also a risk factor for microangiopathy, particularly nephropathy. The incidence of atherosclerotic disease is dramatically increased in both type 1 and type 2 diabetics and is the major cause of morbidity and premature death mainly in patients with raised urinary albumin excretion. Thus, diabetics show a two-fold increased risk of coronary heart disease, 2-6 fold increased risk of stroke and a several-fold increased risk of peripheral vessel disease. Some evidence suggests that hypertension may be a risk factor for retinopathy, particularly its progression, but surely hypertension is a significant risk factor for nephropathy, accelerating its progression and perhaps even causing the onset of the glomerulopathy. The mechanisms by which hypertension might contribute to the evolution of both large vessel as well as small vessel disease is still unknown, although increased capillary leakage and vascular endothelium alterations might be important factors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Hypertension and diabetes]. 856 58

The elevated mRNA levels encoding matrix components in glomeruli isolated from streptozotocin-induced diabetic rats provide evidence that stimulation of matrix synthesis is important in early phases of diabetic glomerulopathy. We and others have demonstrated that high glucose stimulates collagen mRNA levels in short-term mesangial cell culture. To test whether transcriptional activation is operative and to gain insights into the underlying mechanisms, we studied a murine mesangial cell line stably transfected with a minigene expressing luciferase driven by 5'-flanking and first-intron regions of the alpha 1(IV) gene. High glucose stimulated luciferase activity dose and time dependently, with optimal stimulation (two-fold) achieved after 48 h in 450 mg/dL glucose (G450) versus 100 mg/dL (G100). We next tested the involvement of protein kinase C (PKC) because high glucose has been shown to stimulate de novo synthesis of diacylglycerol (DAG). Increasing PKC activity by treatment with a DAG analogue or active phorbol ester stimulated luciferase activity preferentially in G100; addition of the PKC inhibitors staurosporine or calphostin C markedly inhibited luciferase activity preferentially in G450. Thus high glucose promotes transcriptional activity of alpha 1(IV) gene through PKC activation. We also tested the involvement of protein kinase A (PKA). Intracellular cyclic AMP levels were increased two fold after 48 h in G450 versus G100, and addition of 8-Br-cAMP (0.1 mM) preferentially stimulated luciferase activity by almost three fold in G100 versus only 1.2-fold in G450. Hence, the signal-transduction mechanisms underlying the transcriptional activation of alpha 1(IV) gene in mesangial cells by high glucose are mediated by pathways involving the PKC system and possibly the cAMP/PKA system.
J Diabetes Complications
PMID:Role of protein kinase C and cyclic AMP/protein kinase A in high glucose-stimulated transcriptional activation of collagen alpha 1 (IV) in glomerular mesangial cells. 857 41

Hyalinization of juxtaglomerular arterioles is prominent in advanced diabetic nephropathy and may have important functional consequences. We studied the early stages of diabetic renal disease using kidney biopsy material from insulin-dependent diabetic patients, 8 with normal albumin excretion rate (< 15 micrograms/min) and 16 with microalbuminuria (15-200 micrograms/min). Ten living non-diabetic kidney donors served as a control group. Median duration of diabetes was 9.5 years (range 5-31) in patients with normoalbuminuria, and 12 years (7-22) in patients with microalbuminuria (p = 0.27). The tissue was sectioned systematically, 1-micron thick sections for light microscopy at 10-micron intervals, and thin sections for electron microscopy taken at 60-micron intervals. The arterioles were identified as afferent or efferent, and total profiles were photographed (magnification 7500x), providing a systematic independent sample for measurements using standard stereological methods. Patients with microalbuminuria had significantly increased arteriole parameters compared with the control group: for afferent and efferent arterioles the volume fraction of matrix/media, means and (co-efficient of variation, CV), was 0.47 (0.16) vs 0.33 (0.19) (p = 0.0009), and 0.62 (0.14) vs 0.45 (0.23) (p = 0.0004) and matrix-T, expressing amount of matrix per unit arteriolar surface, 2.38 (0.38) micron vs 1.44 (0.30) micron (p = 0.004), and 1.62 (0.28) micron vs. 1.03 (0.34) (p = 0.0009). Patients with normoalbuminuria showed no significant differences from the control group, and had lower values than microalbuminuric patients for all parameters except the afferent matrix-T. In the normoalbuminuric group a correlation was found between parameters for afferent arterioles and those for glomerular structure. In conclusion there is arteriolar accumulation of extracellular material in the early phase of diabetic nephropathy, concomitant with early glomerulopathy.
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PMID:A quantitative ultrastructural study of juxtaglomerular arterioles in IDDM patients with micro- and normoalbuminuria. 858 42

Two hundred and two renal biopsies from 181 patients in New Caledonia were classified into either primary glomerulonephritis or glomerulopathy associated with systemic disease. These were then compared with 670 similar biopsies from 634 in-patients at Sydney's Royal Prince Alfred Hospital (RPAH). The most prevalent primary glomerular disease among the New Caledonian cases was focal segmental glomerulosclerosis, compared with IgA disease among the RPAH cases. Mesangiocapillary glomerulonephritis, post-infectious glomerulonephritis and minimal lesion nephropathy were all relatively commoner among the New Caledonian biopsies, but the numbers were small. The most prevalent systemic glomerulopathy in the New Caledonian cases were amyloidosis. This was the least common among our RPAH group. Diabetes mellitus and lupus nephritis were also slightly more common in the New Caledonian group. Focal necrotizing/crescentic glomerulonephritis was unusual in the New Caledonian samples, while it was the most common systemic glomerulopathy among the RPAH group.
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PMID:The pattern of glomerular disease in New Caledonia: preliminary findings. 871 67

An accurate assessment of which patient with glomerular disease will progress to end-stage renal failure would be an important addition to establishing prognosis and evaluating therapeutic strategies. We previously found the development of glomerular scarring in animal models was preceded by an increase in glomerular type IV collagen mRNAs and that the level of scarring predicted the rate of progression. The purpose of this study was to determine whether these findings apply to human glomerular diseases using microdissected glomeruli and assessment of mRNA by competitive PCR. After showing that the levels of type IV collagen mRNAs were elevated in sclerotic glomeruli isolated from nephrectomies, we undertook this preliminary cross-sectional study of type IV collagen subchain mRNAs in renal biopsies in two of the leading causes of glomerulosclerosis, diabetic nephropathy, and membranous glomerulopathy. We found that glomerular type IV collagen mRNA levels were altered in disease-specific ways. The relative levels of the individual alpha-chains of type IV collagen depended on the anatomic site of the glomerular lesions. The alpha 2 type IV/alpha 3 type IV collagen mRNA ratio was high in diabetes mellitus, but not in membranous glomerulopathy. These data, coupled with those obtained from experimental animals, suggest that a dysregulation of basement collagen synthesis underlies progressive glomerular scarring. If these conclusions are verified in prospective studies it will be feasible to assess the risk of developing progressive glomerulosclerosis in the individual patient and to quantitatively assess therapeutic responses in a timely manner.
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PMID:Molecular analysis of glomerular diseases in renal biopsies: initial results of a collaborative international study. The International Study Group for Molecular Study of Kidney Biopsies. 877 54

Renal haemodynamic changes are suggested to be an early sign of diabetic glomerulopathy. The juxtaglomerular apparatus relevant to the renin angiotensin system, known to be the site of nitric oxide (NO) production, is considered to play a role in the regulation of glomerular blood flow. This study was therefore designed to clarify whether in situ expression of nitric oxide synthase (NOS) is altered in the kidney of diabetic rats. Streptozotocin-induced diabetic rats with 6, 8, 12 and 32 weeks diabetes duration and age-matched normal control rats were used. The expression of a constitutive form of NOS (cNOS, neural type) and NADPH diaphorase activity in the renal cortex were studied immunohistochemically and histochemically. Diabetic rats had lower body weight and heavier kidney mass compared to control rats at each time point examined. Mean glomerular surface area was greater in 6, 8 and 12-week diabetic rats compared to age-matched control rats. cNOS reaction was localized in the macula densa and appeared less intense in diabetic rats compared to age-matched control rats. The mean number of macula densa cells positive for cNOS in each glomerulus and in each glomerular area was significantly lower in diabetic rats compared to control rats at any time examined. In contrast, NADPH diaphorase activity was detected in both juxtaglomerular arterioles and macula densa cells. The staining reaction of NADPH diaphorase in the arterioles remained positive but appeared less intense in macula densa cells in diabetic rats. These results suggest that NO production in macula densa cells may be reduced in diabetic rats, modulating the vasodilatory function of afferent arterioles. Further investigation on the changes in inducible NOS as well as endothelial cNOS are necessary to clarify mechanisms of haemodynamic changes in the diabetic kidney.
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PMID:Expression of nitric oxide synthase in macula densa in streptozotocin diabetic rats. 881 3

In this study, we investigated 1) whether long-term restoration of euglycemia by means of pancreatic islet transplants is capable of preventing and/or reversing renal functional and structural alterations in an experimental model of insulin-deficient diabetes, and 2) whether changes in extracellular matrix (ECM) and cell turnover at the glomerular level and biochemical abnormalities associated with hyperglycemia correlate with the renal outcome after transplantation. Male Lewis rats, rendered diabetic by intravenous injection of streptozotocin, underwent homologous islet transplantation via the portal vein at 2 weeks (study A), at 4 months (study B), and at 8 months (study C) after the induction of diabetes and killed 12 months after transplantation in study A and 4 months after transplantation in studies B and C. Age-matched nondiabetic and untreated diabetic rats were used as control animals and were studied at 4, 8, and 12 months. In the untreated diabetic animals, metabolic derangement was associated with increased erythrocyte polyol and fructose levels, tail-tendon content of advanced glycation end products (AGEs), total proteinuria, albuminuria, kidney weight, and mean glomerular volume as well as with marked glomerular and extraglomerular lesions. Glomerular gene expression for the ECM components fibronectin and collagen IV and for TGF-beta was also increased, whereas glomerular cell proliferation was unaffected by diabetes. In study A, changes in renal function and structure observed in diabetic rats at 12 months were completely prevented by successful islet transplants. In study B, all functional and structural abnormalities detected in diabetic rats at 4 months of disease duration were virtually reversed by 4 months of euglycemia in transplanted animals, whereas they progressed further in untreated diabetic rats. In study C, the course of functional and structural changes observed in untreated diabetic rats was not reversed by islet transplantation. Likewise, tissue AGE accumulation and particularly upregulation of glomerular ECM and transforming growth factor (TGF)-beta gene expression, which are believed to play a role in the pathogenesis of altered renal function and structure in diabetes, were normalized in transplanted rats from study A and study B, but not in those from study C. These experiments show that restoration of euglycemia by islet transplants is capable of preventing experimental diabetic glomerulopathy and reversing early changes in renal function and structure induced by diabetes. In a later phase of the disease, when glomerular matrix gene expression becomes independent of hyperglycemia, possibly because of the persistent increase in tissue AGE accumulation, metabolic control is not capable of reversing renal abnormalities.
Diabetes 1997 Jul
PMID:Early, but not advanced, glomerulopathy is reversed by pancreatic islet transplants in experimental diabetic rats: correlation with glomerular extracellular matrix mRNA levels. 920 Jun 56

A rate of albumin excretion rate above 20 micrograms/min is a predicting factor of overt nephropathy in Type I diabetes. It has not yet been established whether this is the case also for Type II diabetes, where microalbuminuria is antecedent to general and cardiovascular mortality but not to end-stage renal disease. The reasons accounting for this discrepancy between Type I and Type II diabetes have not been fully elucidated. In principle two different hypotheses can be postulated to explain these findings. Firstly it can be suggested that overt proteinuria is not detected with similar incidence rates in microalbuminuric patients with the two types of diseases because Type II diabetics are older and more prone to develop cardiovascular events. Therefore these patients would die frequently before developing overt proteinuria not because microalbuminuria is not a predicting factor of End-stage Renal Disease, but rather because the follow-up period is not long enough to monitor the patients till the very moment they develop renal complications. Alternatively it is possible that microalbuminuria reflect a systemic, endothelial and vascular disorder rather than glomerular structural abnormalities in these patients. We have recently described a clustering of clinical features encompassing microalbuminuria, hypertension, peripheral extrahepatic insulin resistance, renal and cardiac hypertrophy and altered cation membrane transport systems, not in the overall Type II diabetic population, but only in a cohort of these patients. Evidences in keeping with a strict association between insulin resistance, hypertension and microalbuminuria in a subgroup of Type II diabetic patients have been recently reported by several authors both in cross-sectional and longitudinal studies. However the hypothesis that microalbuminuria reflects a systemic endothelial and vascular disorder in Type II diabetic patients, does not rule out the possibility that these systemic disturbances are also associated with histologic abnormalities of the kidney. With regard to the characteristics of renal histology in Type II diabetic patients with and without microalbuminuria, preliminary data from our laboratory demonstrate that there is no evidence of any renal disorder other than diabetes in microalbuminuric Type II diabetic patients. More particularly in this subset of patients we observed typical features of diabetic nephropathology (glomerular, tubulo-interstitial and arteriolar changes), while a substantial number of patients with increased albumin excretion rate exhibited either marked tubulo-interstitial lesions or arteriolar hyalinosis or both, in absence of significant glomerular changes. These findings suggest that it is not true that Type II diabetic patients with microalbuminuria show quite often normal renal histology, but rather than hyperglycemia may cause different patterns of renal injury as compared to Type I Diabetes. Furthermore always with regard to renal histology, it has been pointed out that in Type I diabetes glomerulopathy (especially mesangial) is the crucial change, whereas recent studies found considerable structural heterogeneity amongst proteinuric Type II diabetic patients with relatively high incidence of renal diseases other than diabetes. However parallel studies in a small group of micromacroalbuminuric Type II diabetic patients reported the typical glomerular changes, usually shown by Type I diabetic patients with similar patterns of renal damage. The issue of the relationships between microalbuminuria, hypertension and the development of overt nephropathy in Type II diabetes has been also examined in Pima Indians. The clinical scenario found in these patients does closely resemble that of Caucasian Type I diabetic patients.
Exp Clin Endocrinol Diabetes 1997
PMID:Relationships among microalbuminuria, insulin resistance and renal-cardiac complications in insulin dependent and non insulin dependent diabetes. 928 31


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