Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of proliferative retinopathy in type 2 diabetes mellitus may be under genetic control. A well-documented pathological change in the fundal capillaries of patients with diabetic retinopathy is basement membrane thickening, with an increased amount of collagen IV protein. Variation at the collagen 1a IV gene therefore may explain familial susceptibility to this complication. It has been previously reported that genetic variation at the collagen 1a locus, as shown by allelic association with a HindIII restriction site, predisposes to diabetic nephropathy where basement membrane thickening is also prevalent. In order to test the hypothesis that the collagen 1a IV gene locus is important in the development of diabetic retinopathy, a population association study was performed comparing allele frequencies of the HindIII RFLP in diabetic patients with retinopathy and controls. No statistically significant differences were found between allele frequencies or genotypes in the two groups. The future use of similar studies in diabetic retinopathy is discussed.
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PMID:Genetic variation around the collagen IV 1a gene locus and proliferative retinopathy in type 2 diabetes mellitus. 835 15

We investigated serum levels of type III procollagen aminopeptide (CIII), 7S type IV collagen (CIV), and tissue inhibitor of metalloproteinase (TIMP) in 33 patients with type II diabetes mellitus (DM) without uremia (serum creatinine less than 1.5 mg/dl). The patients were divided into three groups based on measurement of the urinary albumin excretion (UAE) index obtained during two morning outpatient clinic visits: non-proteinuric patients (n = 11), UAE index less than 2.26 mg/mmol Cr; patients with microalbuminuria (n = 15), UAE index of 2.26 - 22.6 mg/mmol Cr; and patients with proteinuria (n = 7), UAE index more than 22.6 mg/mmol Cr. Serum levels of CIV and TIMP in patients with microalbuminuria and proteinuria were significantly higher than non-proteinuric patients (ANOVA, p <0.05). Serum levels of CIII in patients with proteinuria were significantly higher than those in non-proteinuric patients (p < 0.05). There was a significant positive correlation between CIV and TIMP (r = 0.502, p < 0.003), but no correlation was observed between CIII and TIMP. These results demonstrated that serum CIII and CIV increases as diabetic nephropathy progresses in terms of increasing proteinuria in type II DM patients, suggesting feasibility and usefulness of measuring serum CIV and CIII in assessing diabetic nephropathy. The increase in TIMP may be, at least in part, a possible cause for the increase in serum CIV in type II DM patients.
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PMID:Serum type III, IV collagens and TIMP in patients with type II diabetes mellitus. 861 90

In diabetic nephropathy a major current concept for pathogenesis is increased collagen accumulation in the glomerulus by increased collagen synthesis and decreased degradation. In the present study, we tested the hypothesis whether arginine is able to influence kidney lipid peroxidation, glycoxidation, collagen accumulation, glucose-mediated cross-linking, hydroxy radical attack, protein oxidation, nitric oxide formation and albuminuria in the diabetic kk mouse. Ten diabetic kk mice were given arginine 50 mg/kg body weight, 10 diabetic kk mice were not treated and used as negative controls and 10 kk mice were kept as healthy controls. Our results show that oral administration of low-dose arginine reduces kidney collagen accumulation as reflected by kidney hydroxyproline, cross-linking as reflected by pentosidine, lipid peroxidation, glycoxidation as reflected by carboxymethyl lysine, kidney weight and albuminuria in the diabetic kk mouse. Albuminuria in untreated animals was closely correlated with lipid peroxidation. Our results in the spontaneously diabetic kk mouse representing type 2 diabetes mellitus therefore confirm and extend recent findings of collagen reduction by arginine in a different animal model. The mechanism of reducing proteinuria can be assigned to the blocking of lipid peroxidation products by L-arginine.
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PMID:Arginine reduces kidney collagen accumulation, cross-linking, lipid peroxidation, glycoxidation, kidney weight and albuminuria in the diabetic kk mouse. 904 44

Free radical activity may contribute to atherosclerotic lesions which in diabetic subjects may frequently lead to vascular complications. It is known that oxidative stress is associated to diabetes. Protein glycation and glucose oxidation could be possible source of free radicals. 28 non insulin dependent diabetic subjects (NIDDM) were examined. 20 healthy subjects matched for age, sex and for the presence of hypertension and hyperlipidemia were also studied. Hydrogen peroxide, measured by intracellular levels of the fluorescent 2,7-dichloro-fluorescein (DCF), was considered as indicative parameter of free radical production. The results showed that in resting platelets the basal level of hydrogen peroxide was significantly higher in diabetic subjects than in controls. Moreover, after stimulation with thrombin, collagen, phorbol myristate acetate (PMA) and platelet activating factor (PAF), platelets of diabetic subjects generated significantly higher amounts of hydrogen peroxide than controls. Moreover, platelet aggregation induced by adenosine 5'-diphosphate (ADP) and plasma beta TG levels were higher in diabetics than in controls. In diabetic patients platelet free radical production and functional activity are increased and therefore could play a role in the elevated thrombotic risk described in diabetes.
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PMID:Hyperactivity and increased hydrogen peroxide formation in platelets of NIDDM patients. 917 36

Non-insulin-dependent diabetes mellitus, obesity, and essential hypertension are associated with hyperinsulinemia that results from insulin resistance and insulin has been reported to accelerate atherosclerosis. We studied the effects of insulin and insulin-like growth factor-1 (IGF-1) on the growth of porcine vascular smooth muscle cells and on the synthesis of extracellular matrix. The cells were cultured 3-8 changes of Dulbecco's modified Eagle's medium (DMEM) with 10% FCS. Subconfulent cells were put in wells 1 x 10(4) or 1 x 10(5) cells/well in DMEM with or without insulin or IGF-1. The number of cells was counted, and protein and DNA synthesis, expression of genes for collagen alpha1(1), and collagen synthesis were measured. Insulin (0, 16, and 160 nM) and IGF-1 (0, 1, 31, and 13.1 nM) increased number of cells by 50% and 40%, in a dose-dependent manner. Protein and DNA synthesis were also increased by insulin (3.8 and 3.0 times) and by IGF-1 (3.9 and 1.8 time). Collaged protein synthesis was increased 2.3-fold by IGF-1 at 13.1 nM, and insulin (16,000 nM) caused a 26.5-fold increase. Levels of collagen alpha1(1) mRNA were also increased by both insulin and IGF-1. These results suggest that insulin and IGF-1 can cause vascular hyperplasia associated with increased collagen synthesis, which indicates that insulin, IGF-1, or both may have an important role in vascular growth.
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PMID:[Effect of insulin and insulin-like growth factor-1 on vascular smooth muscle cells]. 938 74

Recently, we have developed a highly sensitive assay system for quantitative measurement of urinary type IV collagen. To obtain a basic evaluation of the assay system we used urine specimens, collected randomly and studied the relation to diabetic nephropathy in patients with non-insulin dependent diabetes mellitus (NIDDM). It was shown that this assay system could measure the samples without concentrating the urine. Urinary sediments which were reported to interfere with the assay could be removed by adding Tris-buffer. In the clinical studies, urinary type IV collagen concentrations were significantly higher in patients with NIDDM regardless of the presence or the absence of albumin. Cases with abnormal values of urinary type IV collagen in the normal albuminuria group were 41.6%, while those with abnormal values of urinary transferrin excretion were 31.0%. Furthermore, among the normal albuminuria group, glycosylated hemoglobin (HbA1c) levels were higher in the groups of abnormal values of urinary type IV collagen than those within the reference values. These results obtained herein suggest that urinary type IV collagen could be a useful marker for the early stage of diabetic nephropathy.
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PMID:[The significance of determination of urinary type IV collagen concentrations from a random urine collection in patients with non-insulin dependent diabetes mellitus]. 956 68

Glycation and free radical reactions may play a role in complications of diabetes. Vascular complications, as a consequence of atherosclerosis, are the main causes of morbidity and mortality in diabetes. The aim of this work was to study glycation and lipid peroxidation (LPO) in plasma and skin of type 2 diabetic patients. The levels of advanced glycation endproducts (AGEs) in skin collagens are considered as the sum of accumulated glycation over time. We studied 20 subjects with type 2 diabetes and 20 controls. Glycated proteins were quantified in skin and plasma by affinity chromatography in aminophenyl boronate gels. AGEs were determined on skin collagen by fluorimetry. LPO was evaluated by fluorimetry measuring TBARS in the skin and plasma. Skin collagen-linked fluorescence (CLF) was higher in diabetics (p < 0.01). CLF in diabetics with retinopathy was higher than that of diabetics without retinopathy (p < 0.02). There was a positive correlation between duration of diabetes and skin CLF (p < 0.01). TBARS were higher in skin (p < 0.01) and plasma (p < 0.001) of diabetic patients. We did not find any correlation between CLF and TBARS. This is not surprising taking into account the complexity and multifactorial aspects involved in LPO, while in glycation the main determinant factor is hyperglycemia.
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PMID:[Glycosylation and lipid peroxidation in skin and in plasma in diabetic patients]. 958 89

Non-enzymatic glycosylation (NEG) of collagen has been previously shown to significantly influence the reactive oxygen metabolism (ROM) of phagocytic cells in healthy subjects. Considering the role of NEG in the pathophysiology of diabetes, we have further analysed the oxidative metabolism of polymorphonuclear cells (PMNs) and monocytes in 23 patients with non-insulin dependent diabetes mellitus in order to better elucidate a possible pathogenic role of NEG of the extracellular matrix in long-term complications of diabetes. Experiments were performed in triplicate on native-collagen and glycated-collagen coated vials, using a chemiluminescence (CL) assay. Results show that PMNs from diabetic patients display a significant increased basal and zymosan-induced CL activity with respect to controls that are not related to the glycation state of the substrate. Conversely, the CL activity of monocytes induced by zymosan shows a decrease in diabetic patients with respect to healthy volunteers (p < 0.05). Moreover, monocyte CL was reduced by the glycated matrix, both in healthy volunteers and in diabetic subjects (p < 0.05 and p < 0.01, respectively). These data highlight a complex role of phagocytic leukocytes in the pathophysiology of extracellular matrix alterations secondary to NEG that are typically present in clinical conditions such as diabetes or ageing.
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PMID:Impaired reactive oxygen metabolism of phagocytic leukocytes in NIDDM patients. A role for non-enzymatic glycosylation of collagen. 983 91

Activation of protein kinase C (PKC) is implicated as an important mechanism by which diabetes causes vascular complications. We have recently shown that a PKC beta inhibitor ameliorates not only early diabetes-induced glomerular dysfunction such as glomerular hyperfiltration and albuminuria, but also overexpression of glomerular mRNA for transforming growth factor beta1 (TGF-beta1) and extracellular matrix (ECM) proteins in streptozotocin-induced diabetic rats, a model for type 1 diabetes. In this study, we examined the long-term effects of a PKC beta inhibitor on glomerular histology as well as on biochemical and functional abnormalities in glomeruli of db/db mice, a model for type 2 diabetes. Administration of a PKC beta inhibitor reduced urinary albumin excretion rates and inhibited glomerular PKC activation in diabetic db/db mice. Administration of a PKC beta inhibitor also prevented the mesangial expansion observed in diabetic db/db mice, possibly through attenuation of glomerular expression of TGF-beta and ECM proteins such as fibronectin and type IV collagen. These findings provide the first in vivo evidence that the long-term inhibition of PKC activation in the renal glomeruli can ameliorate glomerular pathologies in diabetic state, and thus suggest that a PKC beta inhibitor might be an useful therapeutic strategy for the treatment of diabetic nephropathy.
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PMID:Amelioration of accelerated diabetic mesangial expansion by treatment with a PKC beta inhibitor in diabetic db/db mice, a rodent model for type 2 diabetes. 1069 58

Poorly controlled type 2 or non-insulin dependent diabetes mellitus (NIDDM) patients exhibit high bone turnover, which decelerate with treatment according to the degree of improvement in glycemic control. In adults, higher bone turnover results in rapid bone loss. Therefore, deceleration of bone turnover is beneficial for bone. Troglitazone (Tro), a new anti-diabetic drug, is a thiazolidinedione (TZD) which promotes adipocyte differentiation by activating peroxisome proliferator activated receptor gamma (PPARgamma). Because, in the bone marrow, adipocytes and osteoblasts originate in common mesenchymal stem cells that are also essential for osteoclastogenesis, TZDs may directly affect bone metabolism. Thus, we examined the effects of Tro on metabolic bone markers in type 2 DM patients. Tro (400 mg/day) was administered to 33 type 2 DM patients for four weeks. The day before and four weeks after starting Tro, serum and urine samples were collected after overnight fasting. Metabolic bone markers and glycemic indices were assessed. As bone resorption markers, urinary free and total deoxypyridinoline as well as urinary collagen type I C-terminal telopeptide were measured; as bone formation markers, serum bone type and total alkaline phosphatase (BALP and ALP) levels along with osteocalcin (OC) were used. No significant changes in fasting plasma glucose or HbA1c levels were observed in our short-term treatment with Tro. All the bone resorption markers, BALP and ALP were significantly decreased. OC was not significantly changed. The discrepant changes of OC from all the other metabolic bone markers suggest limitation of the use of OC as a reliable bone formation marker in diabetics. Our results that Tro decreased metabolic bone markers before significantly improving glucose metabolism suggest that it has direct effects on bone and decreased bone turnover. TZDs may spare bone mass in NIDDM subjects through its dual effects on glucose and bone metabolism.
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PMID:Short-term treatment with troglitazone decreases bone turnover in patients with type 2 diabetes mellitus. 1072 55


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