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

A protocol has been developed for rapid isolation of albumin from rabbit or bovine serum. It is based on the use of microporous plastic silica sheets that have been fabricated into rapid flow-through devices called ACTI-MOD cartridges. In the first step, the untreated silica plastic matrix binds a major portion of the non-albumin protein. A second step, using an ACTI-MOD anion-exchange quaternary amine, further purifies and concentrates the albumin. At this stage, the albumin appears to be at least ninety-nine per cent pure based on sodium dodecyl sulfate gel electrophoresis.
 ...
PMID:Rapid isolation of serum albumin using microporous PVC/silica cartridges. 131 42

It is clearly recognized that patients with NIDDM have an increased risk for CHD. Recent data indicate that persons with glucose concentrations in the nondiabetic range also may be at higher risk for CHD. These associations may not represent cause and effect, however. Emerging data suggest that hyperglycemia and CHD may both arise from hyperinsulinemia/insulin resistance. In support of this hypothesis are studies showing that NIDDM and CHD have many risk factors in common, including age, elevated blood pressure, dyslipidemia, adiposity, and a central pattern of fat distribution. Moreover, these risk factors are frequent concomitants of hyperinsulinemia, itself a risk factor for CHD and perhaps for NIDDM. Although the duration of NIDDM has been infrequently related to risk of CHD, the authors hypothesize that duration of hyperinsulinemia/insulin resistance would be a more sensitive marker for risk of CHD. The relation of IDDM to CHD is a different situation. The etiological process leading to IDDM, namely the destruction of beta-cells in genetically predisposed persons, is not related to cardiovascular risk. However, IDDM patients still have an excess of CVD, the risk factors for which may vary according to the location of the diseases (e.g., LEAD vs. CHD). There is a strong relationship between proteinuria and CVD, which has led to a general theory of vascular complications in IDDM based on defective heparan sulfate metabolism (Steno hypothesis). Recent evidence challenges parts of this hypothesis, and the possibility is raised that a higher case-fatality rate in a subgroup of patients with both renal and CVD explains part of the renal connection, as does the general worsening of CVD risk factors.
 ...
PMID:Diabetes mellitus and macrovascular complications. An epidemiological perspective. 139 12

Amyloid in the islets of Langerhans is the uniform pathologic feature in the pancreata of patients with type II diabetes mellitus. Although the mechanisms of islet amyloid fibrillogenesis are unknown, the presence of heparan sulfate proteoglycan in many other forms of amyloid suggests a role for this proteoglycan in amyloidogenesis in general. In this study, islet amyloid was evaluated for the presence of the basement membrane heparan sulfate proteoglycan using histochemical and immunohistochemical techniques. Staining with sodium sulfate-alcian blue identified highly sulfated glycosaminoglycans within all islet amyloid deposits, and anti-basement membrane heparan sulfate proteoglycan antisera localized this specific proteoglycan within the islet amyloid. The presence of the basement membrane heparan sulfate proteoglycan links islet amyloid to other disparate forms of amyloid and further supports the hypothesis that it has a role in a common pathway of amyloid fibrillogenesis.
 ...
PMID:Localization of the basement membrane heparan sulfate proteoglycan in islet amyloid deposits in type II diabetes mellitus. 152 61

Decreased serum zinc levels and hyperzincuria occur in some non-insulin dependent diabetic subjects (NIDDM). Zinc deficiency was demonstrated in various tissues of animal models for NIDDM. Serum zinc and 24-hr urine zinc of subjects with NIDDM were compared with that of age- and sex-matched healthy volunteers. Zincuria was significantly increased in the diabetic group. Thirteen diabetic subjects with hyperzincuria and hypozincemia were supplemented with zinc sulfate 220 mg x 3/day for 7-8 weeks. At the end of the study, glucose disposal (evaluated by kg) decreased significantly from 0.562 +/- 0.03 to 0.414 +/- 0.05 (p less than 0.05) and fasting glucose and fructosamine were significantly increased from 177 +/- 10 mg/dl to 207 +/- 15 mg/dl (p less than 0.05) and from 2.7 +/- 0.2% to 3.2 +/- 0.28% (p less than 0.05), respectively. T-lymphocyte response to phytohemagglutinin was increased significantly. We conclude that zinc supplementation to NIDD patients with hypozincemia and hyperzincemia might aggravate their glucose intolerance. More accurate methods to assess zinc deficiency in NIDD patients is needed to justify the supplementation of zinc in these patients.
 ...
PMID:The influence of zinc supplementation on glucose homeostasis in NIDDM. 269 82

Glomerular proteoglycans (PG) are important in modulating extracellular matrix assembly and glomerular permselectivity. In the obese Zucker rat, an experimental model of non-insulin dependent diabetes mellitus, expansion of the mesangial matrix, and microalbuminuria occur before the development of overt renal disease. The in vivo incorporation of (35S)sulfate into glomerular PG in 12-wk-old obese Zucker rats at the onset of microalbuminuria was compared with that of 12-wk-old lean Zucker rats. Specific (35S)sulfate incorporation into glomerular PG over 8 h was increased by 57% in obese rats compared with lean rats, suggesting increased PG synthesis. However, at variance with the observation in experimental models of insulin-dependent diabetes mellitus, the proportion of total glomerular (35S)PG released by heparin treatment was unchanged. Heparan sulfate (HS)-PG constituted over 60% of radiolabeled de novo synthesized glomerular PG. Similar proportions of HS-PG were extracted from the glomeruli of obese and lean rats. Isolated glomeruli spontaneously released two HS-PG, which constituted approximately 30% of total glomerular (35S)PG. On the basis of their chromatographic and electrophoretic patterns, these PG were similar in obese and lean rats. Heparin treatment of isolated glomeruli released an additional HS-PG, which appeared to be derived primarily from the glomerular extracellular matrix compartment and not from the detergent soluble cell fraction. Heparin-releasable HS-PG from both the lean and obese Zucker rats eluted at a KAV of 0.31 from Sepharose CL-6B chromatographic columns, indicating a hydrodynamic size similar to that reported for glomerular basement membrane HS-PG. However, gel electrophoresis demonstrated faster migration of the HS-PG released by heparin from the glomeruli of obese Zucker rats, suggesting increased electronegativity. Thus, early in the course of nephropathy in the obese Zucker rat, there is increased glomerular PG synthesis with no change in the proportions of the constitutively releasable and heparin-releasable HS-PG. Whether electrophoretic abnormalities of the heparin-releasable HS-PG observed in the obese rats contribute to the development of albuminuria and/or mesangial matrix expansion remains to be established.
 ...
PMID:Alterations in glomerular proteoglycan metabolism in experimental non-insulin dependent diabetes mellitus. 831 86

We compared the effects of oral vanadyl sulfate (100 mg/day) in moderately obese NIDDM and nondiabetic subjects. Three-hour euglycemic-hyperinsulinemic (insulin infusion 30 mU / m / min) clamps were performed after 2 weeks of placebo and 3 weeks of vanadyl sulfate treatment in six nondiabetic control subjects (age 37 +/- 3 years; BMI 29.5 +/- 2.4 kg/m2 ) and seven NIDDM subjects (age 53 +/- 2 years; BMI 28.7 +/-1.8 kg/m2). Glucose turnover ([3-3 H]glucose), glycolysis from plasma glucose, glycogen synthesis, and whole-body carbohydrate and lipid oxidation were evaluated. Decreases in fasting plasma glucose (by approximately 1.7 mmol/l) and HbAlc (both P < 0.05) were observed in NIDDM subjects during treatment; plasma glucose was unchanged in control subjects. In the latter, the glucose infusion rate (GIR) required to maintain euglycemia (40.1 +/- 5.7 and 38.1 +/- 4.8 micromol / kg fat-free mass FFM / min) and glucose disposal (Rd) (41.7 +/- 5.7 and 38.9 +/-4.7 micromol / kg FFM / min were similar during placebo and vanadyl sulfate administration, respectively. Hepatic glucose output (HGO) was completely suppressed in both studies. In contrast, in NIDDM subjects, vanadyl sulfate increased GIR approximately 82% (17.3 +/- 4.7 to 30.9 +/- 2.7 micromol / kg FFM / min, P < 0.05); this improvement in insulin sensitivity was due to both augmented stimulation of Rd (26.0 +/-4.0 vs. 33.6 +/- 2.22 micromol / kg FFM / min, P < 0.05) and enhanced suppression of HGO (7.7 +/- 3.1 vs. 1.3 +/- 0.9 micromol / kg FFM / min, P < 0.05). Increased insulin-stimulated glycogen synthesis accounted for >80% of the increased Rd with vanadyl sulfate (P < 0.005), but plasma glucose flux via glycolysis was unchanged. In NIDDM subjects, vanadyl sulfate was also associated with greater suppression of plasma free fatty acids (FFAs) (P < 0.01) and lipid oxidation (P < 0.05) during clamps. The reduction in HGO and increase in Rd were both highly correlated with the decline in plasma FFA concentrations during the clamp period (P < 0.001). In conclusion, small oral doses of vanadyl sulfate do not alter insulin sensitivity in nondiabetic subjects, but it does improve both hepatic and skeletal muscle insulin sensitivity in NIDDM subjects in part by enhancing insulin's inhibitory effect on lipolysis. These data suggest that vanadyl sulfate may improve a defect in insulin signaling specific to NIDDM.
 ...
PMID:Oral vanadyl sulfate improves insulin sensitivity in NIDDM but not in obese nondiabetic subjects. 862 Oct 19

Islet amyloidosis is characterized by the deposition and accumulation of amylin in pancreatic beta-cells and is observed in 90% of patients with type 2 diabetes. Previous studies have also revealed the presence of the specific heparan sulfate proteoglycan, perlecan, colocalized to islet amyloid deposits, similar to perlecan's known involvement with other amyloid proteins. In the present study, perlecan purified from the Engelbreth-Holm-Swarm (EHS) tumor was used to define perlecan's interactions with amylin (i.e., islet amyloid polypeptide) and its effects on amylin fibril formation. Using a solid phase-binding immunoassay, human amylin, but not rat amylin, bound immobilized EHS perlecan with a single dissociation constant (Kd) = 2.75 x 10(-6) mol/l. The binding of human amylin to perlecan was similarly observed using perlecan heparan sulfate glycosaminoglycans (GAGs), and was completely abolished by 10 micromol/l heparin. Using thioflavin T fluorometry, Congo red staining, and electron microscopy methodology, intact perlecan was found to enhance amylin fibril formation in a dosage-dependent manner, with the majority of these effects attributed to the heparan sulfate GAG chains of perlecan. Other sulfated GAGs and related macromolecules were also effective in the enhancement of amylin fibril formation in the order of heparin > heparan sulfate > chondroitin-4-sulfate = dermatan sulfate = dextran sulfate > pentosan polysulfate, implicating the importance of the specific GAG/carbohydrate backbone. The sulfate content of heparin/heparan sulfate was also important for the enhancement of amylin fibril formation in the order of heparin > N-desulfated N-acetylated heparin > completely desulfated N-sulfated heparin > completely desulfated N-acetylated heparin. These studies suggest that the enhancement effects of perlecan on amylin fibril formation are mediated primarily by both specific GAG chain backbone and GAG sulfate content, and implicate perlecan as an important macromolecule that is likely involved in the pathogenesis of islet amyloidosis.
 ...
PMID:Sulfate content and specific glycosaminoglycan backbone of perlecan are critical for perlecan's enhancement of islet amyloid polypeptide (amylin) fibril formation. 956 95

Familial hypobetalipoproteinemia is caused by mutations in the apolipoprotein (apo) B gene. We identified a 57-year-old woman whose plasma total cholesterol and apoB levels were 2.17 mmol/L and 0.03 g/L, respectively. Separation of plasma lipoproteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the absence of apoB-100 and the presence of a faster-migrating form of apoB with an apparent Mr of 195 kDa. Direct sequencing of a polymerase chain reaction-amplified fragment of the patient's apoB gene DNA revealed a single C-->T transition at nucleotide 5472 that converts glutamine 1755 (CAA) to a stop codon (TAA). We predict this novel nonsense mutation of the apoB gene to produce a truncated protein that contains 1754 amino-terminal amino acid residues of apoB-100. We designated this mutant form of apoB apoB-38.7 by following the centile nomenclature of the apoB species. The same mutation was found in both of her children. The proband revealed clinical findings of retinitis pigmentosa, acanthocytosis, and loss of deep tendon reflexes that are characteristic of severe hypobetalipoproteinemia. In addition, the proband had type II diabetes mellitus with nephropathy, anemia, cholelithiasis, hepatic hemangioma, bronchiectasis, and extensive calcification of major arteries including, the celiac, splenic, and renal. In summary, we have found a novel truncated apoB, apoB-38.7, in a patient with an unusual presentation of hypobetalipoproteinemia that includes diabetes mellitus and extensive arterial calcification.
 ...
PMID:A truncated species of apolipoprotein B (B-38.7) in a patient with homozygous hypobetalipoproteinemia associated with diabetes mellitus. 971 41

The polycystic ovary syndrome (PCOS) is a common hyperandrogenic disorder and is characterized by a constellation of signs and symptoms often in association with a family history of hyperandrogenism and/or PCOS. It is often associated with hyperinsulinism and insulin resistance, which puts patients at risk for possible potential complications including type 2 diabetes mellitus and cardiovascular disease. Clinical signs may be subtle, and biochemical markers most often include an elevation of free testosterone (T) and possibly dehydroepiandrosterone sulfate (DHEAS). The diagnosis should be sought in any woman with hyperandrogenic features so that appropriate treatment may be used. There is often a good therapeutic response of the hirsutism, acne, or oligomenorrhea associated with PCOS. The new modalities that increase insulin sensitivity as well as weight reduction in the obese woman with PCOS may potentially be useful in modifying the potential later complications of this common endocrinopathy of young adult women.
 ...
PMID:Polycystic ovary syndrome: clinical perspectives and management. 1035 53

In diabetic nephropathy, heparan sulfate glycosaminoglycan side chains are reduced in glomerular basement membranes proportionally to the degree of proteinuria. Recently, it was demonstrated that additional therapy with danaparoid sodium, a mixture of sulfated glycosaminoglycans with mainly heparan sulfate, lowered proteinuria in type 1 diabetes patients with diabetic nephropathy. A randomized placebo-controlled parallel study was performed with 750 anti-Xa units of danaparoid sodium once daily in type 2 diabetes patients with severe proteinuria. The aim of the study was to evaluate the possible effects of danaparoid sodium on proteinuria, endothelial dysfunction, and hard exudates in the retina and to determine the safety/tolerability of this drug. Twenty-two patients completed the study, and one patient had to stop prematurely after 6 wk of danaparoid sodium treatment because of urticaria at the injection sites. Apart from a small decrease of hemoglobin and minor skin hematomas at the injection site in five patients in the danaparoid sodium group, no other safety parameters showed any clinically or statistically significant difference between and within groups. The relative change in time of both the urinary albumin and protein excretion rate corrected for creatinine did not differ between both treatment arms (P = 0.2 and 0.49, respectively). No retinal complications or changes of hard exudates occurred. von Willebrand factor was elevated in both groups, but was not influenced by either treatment modality. Contrary to the beneficial effects that occurred in type 1 diabetes patients with diabetic nephropathy, treatment for 8 wk with 750 anti-Xa units of danaparoid sodium gave no reduction of proteinuria, hard exudates, and von Willebrand factor.
 ...
PMID:Effect of danaparoid sodium on proteinuria, von Willebrand factor, and hard exudates in patients with diabetes mellitus type 2. 1036 73


1 2 3 4 5 6 7 8 9 10 Next >>