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)

Changes in urine retinol binding protein (RBP, M(r) 21,000) excretion and other indices of renal tubular damage were investigated in the patients with non-insulin dependent diabetes mellitus (NIDDM). Changes in urine RBP excretion were well paralleled with those of urine NAG excretion. In RBP-negative patients, the subjects with hypertension (systolic blood pressure > or = 140 mmHg or diastolic blood pressure > or = 90 mmHg) showed higher beta 2-microglobulin (beta 2-MG) excretion and albumin (Alb)/Cr ratios than normotensive ones. In addition, both urine beta 2-MG excretions and Alb/Cr ratios were significantly increased in RBP-positive patients. The measurement of urine RBP excretion may have an additional role in the diagnosis of renal tubular dysfunction in diabetic patients.
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PMID:Changes in urinary retinol binding protein excretion and other indices of renal tubular damage in patients with non-insulin dependent diabetes. 1803 43

The effect of dietary composition on concentrations of postprandial lipoproteins was studied in eight sulfonylurea-treated patients with noninsulin dependent diabetes mellitus. Two diets were consumed by each patient for 2 weeks in random order, one contained (as percent of total calories) 15% protein, 40% fat, and 45% carbohydrate (CHO), whereas the other consisted of 15% protein, 25% fat, and 60% CHO. At the end of each dietary period, patients were given Vitamin A (60,000 U/m2) with their noon meal, and the concentration of triglyceride (TG) and retinyl esters in plasma and two lipoprotein fractions (Sf > 400 and Sf 20-400) determined over the next 12 h. The results indicated that both postprandial TG and retinyl ester concentrations were higher in plasma (Sf > 400, and Sf 20-400 lipoproteins), when patients ate the 25% fat/60% CHO diet. Thus, replacing saturated fat with CHO accentuates the magnitude of postprandial lipemia. Since TG-rich lipoproteins may be atherogenic, appropriate dietary advice for patients with type 2 diabetes may deserve reappraisal.
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PMID:Effect of variations in dietary fat and carbohydrate intake on postprandial lipemia in patients with noninsulin dependent diabetes mellitus. 843 77

Recent studies have shown that plasma concentrations of vitamin A (retinol) and its carrier proteins, retinol-binding protein (RBP), and transthyretin (TTR), are decreased in human subjects with insulin-dependent (IDDM) but not with noninsulin dependent diabetes mellitus (NIDDM). Rats made diabetic with streptozotocin (STZ) have also been shown to have reduced levels of plasma vitamin A while its hepatic concentrations elevate. The circulatory vitamin A levels remained low while its hepatic concentrations were further elevated following supplementation of the vitamin. The reduced circulatory status of vitamin A in diabetic animals was not caused by its impaired intestinal absorption. Further experimental studies have pointed to the fact that IDDM is associated with a deficiency of vitamin A, which is secondary to an impaired transport mechanism of this vitamin from its hepatic storage to the target site, such as retina of the eyes. The diabetes-associated changes in vitamin A metabolism were reserved to normal by insulin treatment. The underlying cause for decreased metabolic availability in uncontrolled diabetes, is not clearly understood. It appears that the increased hepatic store of vitamin A is attributed to a decreased availability of its carrier proteins. Subnormal vitamin A status in poorly controlled diabetic subjects may not respond to vitamin A supplementation, rather it may increase its load in the liver leading to hepatoxicity. These results clearly suggest that there is need for further research identifying the importance of vitamin A in diabetes mellitus.
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PMID:Vitamin A homeostasis and diabetes mellitus. 999 May 81

Before permanent European colonization 2 centuries ago, Australian Aborigines were preagriculturalist hunter-gatherers who had adapted extraordinarily well to life in a variety of habitats ranging from tropical forests, coastal and riverine environments, savannah woodlands, and grasslands to harsh, hot, and very arid deserts. Colonization had serious negative effects on Aboriginal society, well-being, and health, so much so that Aborigines are now the unhealthiest subgroup in Australian society. The change from active and lean hunter-gatherers to a more sedentary group of people whose diet is now predominantly Westernized has had, and continues to have, serious effects on their health, particularly in relation to cardiovascular disease and type 2 diabetes mellitus, which are highly prevalent among Aborigines. The contemporary diets of Australian Aborigines are energy rich and contain high amounts of fat, refined carbohydrates, and salt; they are also poor in fiber and certain nutrients, including folate, retinol, and vitamin E and other vitamins. Risks of development of cardiovascular disease and type 2 diabetes in this population probably develop during late childhood and adolescence. This indicates a need for greater emphasis on health promotion and disease prevention than at present and a need to plan these in culturally sensitive, secure, and appropriate ways. Most information about Aboriginal diets is anecdotal or semiquantitative. More effort needs to be invested in studies that more clearly and precisely define dietary patterns in Aboriginal people, especially children, and how these patterns influence their growth, nutritional status, and health, prospectively.
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PMID:Historical, cultural, political, and social influences on dietary patterns and nutrition in Australian Aboriginal children. 1106 78

In obesity and type 2 diabetes, expression of the GLUT4 glucose transporter is decreased selectively in adipocytes. Adipose-specific Glut4 (also known as Slc2a4) knockout (adipose-Glut4(-/-)) mice show insulin resistance secondarily in muscle and liver. Here we show, using DNA arrays, that expression of retinol binding protein-4 (RBP4) is elevated in adipose tissue of adipose-Glut4(-/-) mice. We show that serum RBP4 levels are elevated in insulin-resistant mice and humans with obesity and type 2 diabetes. RBP4 levels are normalized by rosiglitazone, an insulin-sensitizing drug. Transgenic overexpression of human RBP4 or injection of recombinant RBP4 in normal mice causes insulin resistance. Conversely, genetic deletion of Rbp4 enhances insulin sensitivity. Fenretinide, a synthetic retinoid that increases urinary excretion of RBP4, normalizes serum RBP4 levels and improves insulin resistance and glucose intolerance in mice with obesity induced by a high-fat diet. Increasing serum RBP4 induces hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) and impairs insulin signalling in muscle. Thus, RBP4 is an adipocyte-derived 'signal' that may contribute to the pathogenesis of type 2 diabetes. Lowering RBP4 could be a new strategy for treating type 2 diabetes.
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PMID:Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. 1603 6

Retinol (vitamin A) is an example of a small molecule that is essential for higher organisms; its utilisation has been involved in the evolution of a number of proteins. In mammalian species, retinol is obtained from the diet and controls the release of its binding protein from hepatocytes into the blood stream. Subsequent influx into cells under normal situations usually involves a specific membrane-bound receptor for retinol-binding protein, which facilitates the uptake of retinol alone or bound to its carrier. This specific receptor has not yet been identified, but a receptor for a related lipocalin has been cloned. It represents a relatively new family, and there are a number of related genes in various eukaryotic genomes, suggesting that the system is very widespread in multicellular organisms. Its significance has been highlighted recently by the suggestion that retinol-binding protein, through its receptor, may play a major role in type 2 diabetes, perhaps the greatest scourge of modern society. This system may provide a new paradigm in mammalian biology, another example of which may exist in the processes responsible for steroid handling. This review outlines the characteristics of retinol utilisation in mammalian species, focusing primarily on the uptake system.
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PMID:The retinol-binding protein system: a potential paradigm for steroid-binding globulins? 1670 9

Increased levels of retinol binding protein 4 (RBP4) in serum is associated with insulin resistance. To examine this further, the genomic region of RBP4 was genetically surveyed in Mongolian people, who as a group are suffering from a recent rapid increase in diabetes. The RBP4 gene was screened by DHPLC system, and the PCR fragments which showed heteroduplex peaks in multiple samples were followed by direct sequencing to identify common polymorphisms in 48 Mongolian diabetic samples. Identified single nucleotide polymorphisms (SNPs) were genotyped in 511 control and 281 type 2 diabetes samples. The functions of SNPs in the regulatory region were assessed by reporter gene assay and electrophoretic mobility shift assay. Possible association between functional SNPs and serum RBP4 levels or metabolic parameters was statistically assessed. Nine SNPs were identified in the RBP4 gene. A case-control study revealed that the rare alleles of four SNPs were associated with increased risk of diabetes, even after Bonferroni correction (-803, G > A, P = 0.0054; +5169, C > T, P = 0.0025; +6969, G > C, P = 0.0015; +7542, T > del, P = 0.0015). The -803 G > A SNP influenced the transcription efficiency in a hepatocarcinoma cell line as well as the binding efficiency of hepatocyte nuclear factor 1 alpha to the motif. In addition, the -803 A allele was associated with increased serum RBP4 levels in diabetic patients. We have identified a functional SNP in the RBP4 gene associated with type 2 diabetes in Mongolian people.
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PMID:Identification of a regulatory SNP in the retinol binding protein 4 gene associated with type 2 diabetes in Mongolia. 1700 70

Serum retinol binding protein 4 (RBP4) was recently described as a new adipokine that reduced peripheral and hepatic insulin sensitivity and increased hepatic gluconeogenesis. The RBP4 gene maps to 10q23-24, near a region linked to T2DM in Caucasian and Mexican American populations. Hence, sequence variants that alter RBP4 expression or function could increase T2DM susceptibility and reduce insulin sensitivity. We screened the 6 exons, flanking intronic sequence, and 5' and 3' flanking sequences in 48 Caucasian and 48 African American subjects. We identified 21 SNPs, of which 8 were unique to the African American population. Additional public database SNPs were chosen for regions not screened. We selected SNPs for typing based on frequency, linkage disequilibrium, and location in a putative functional or conserved region. We typed 10 SNPs in 191 Caucasians with T2DM and a family history of T2DM, and 188 euglycemic controls with no family history of diabetes. We similarly typed 14 variants in 182 controls and 353 diabetic individuals of African American ancestry. No single variant was associated with type 2 diabetes in either population (p>0.15 in African Americans, p>0.09 in Caucasians), but a haplotype of 8 common SNPs in Caucasians was significantly increased in type 2 diabetics compared with controls (0.137 vs. 0.076, p=0.008). Furthermore, SNPs -804 and +9476 were associated with reduced insulin secretion, (p=0.01 and 0.001, respectively), and SNP +390 with reduced insulin sensitivity (p=0.0005) in Caucasians. Our data suggest that noncoding SNPs may increase diabetes susceptibility in Caucasians and may contribute to insulin resistance and reduced insulin secretion.
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PMID:Retinol binding protein 4 as a candidate gene for type 2 diabetes and prediabetic intermediate traits. 1717 34

DNA microarrays have provided medical researchers with a powerful tool to study the mechanisms of complex diseases, including obesity and type 2 diabetes (T2D). The technology has been used to dissect virtually every aspect of the genetic and molecular basis of these two diseases. Gene expression profiling is the major application of DNA microarrays so far. Subcutaneous fat, visceral fat, adipocyte and preadipocyte, muscle, liver, pancreas and specific nuclei in the hypothalamus under normal and disease conditions are used in addressing the profile of gene expression in obesity and T2D. Comparisons of fat depots in humans and animal models - including ob/ob and db/db mice, diet-induced obese mice, fa/fa Zucker rats, gene knockout (plin (-/-), GLUT4 (-/-)) and transgenic mice (GLUT4-Tg) - have been employed in microarray experiments. The effects of various interventions, such as hormonal and drug treatments, exercise, and surgery, have been studied to determine the expression profile of different developmental stages in cells and the effect of treatment on the two diseases. In this review, the application of microarrays in elucidating the role of retinol binding protein 4 as a link between obesity and T2D is discussed. The possible role in obesity of a common genetic variant near the INSIG2 gene and the discovery of the BBS9 gene are also discussed. The problems and challenges are summarized under eight categories and suggestions for the future direction of research in this area are proposed.
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PMID:Application of DNA microarrays in the study of human obesity and type 2 diabetes. 1741 94

Plasma retinol-binding protein 4 (RBP4) may be a new adipokine linked to obesity-induced insulin resistance and type 2 diabetes. The impact of diabetic nephropathy on plasma RBP4 levels, however, is not known. We tested the hypothesis that microalbuminuria is associated with elevated plasma concentrations of RBP4 in type 2 diabetic subjects. Retinol, its binding protein and transthyretin (TTR) were measured in the plasma and urine of 62 type 2 diabetic subjects, 26 of whom had microalbuminuria. The results were compared to 35 healthy control subjects. Despite no differences in plasma retinol, concentrations of the RBP4 were significantly elevated in plasma of diabetic patients and significantly higher in those with microalbuminuria. The higher plasma levels of the binding protein in subjects with microalbuminuria were accompanied by both significantly elevated plasma TTR and increased urinary levels of RBP4. There were no correlations of plasma-binding protein levels and parameters of insulin resistance. Our study suggests that plasma RBP4 levels in type 2 diabetic patients are affected by incipient nephropathy. Therefore, further studies evaluating RBP4 as a regulator of systemic insulin resistance and type 2 diabetes will need to take renal function into consideration.
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PMID:Microalbuminuria is a major determinant of elevated plasma retinol-binding protein 4 in type 2 diabetic patients. 1756 82


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