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

Vitamin A (retinoid) is required in the adult brain to enable cognition, learning, and memory. While brain levels of retinoid diminish over the course of normal ageing, retinoid deficit is greater in late onset Alzheimer disease (LOAD) brains than in normal-aged controls. This paper reviews recent evidence supporting these statements and further suggests that genes necessary for the synthesis, transport and function of retinoid to and within the ageing brain are appropriate targets for treatment of LOAD. These genes tend to be clustered with genes that have been proposed as candidates in LOAD, are found at chromosomal regions linked to LOAD, and suggest the possibility of an overall coordinated regulation. This phenomenon is termed Chromeron and is analogous to the operon mechanism observed in prokaryotes. Suggested treatment targets are the retinoic-acid inactivating enzymes (CYP26)s, the retinol binding and transport proteins, retinol-binding protein (RBP)4 and transthyretin (TTR), and the retinoid receptors. TTR as a LOAD target is the subject of active investigation. The retinoid receptors and the retinoid-inactivating enzymes have previously been proposed as targets. This is the first report to suggest that RBP4 is an amenable treatment target in LOAD. RBP4 is elevated in type-2 diabetes and obesity, conditions associated with increased risk for LOAD. Fenretinide, a novel synthetic retinoic acid (RA) analog lowers RBP4 in glucose intolerant obese mice. The feasibility of using fenretinide either as an adjunct to present LOAD therapies, or on its own as an early prevention strategy should be determined.
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PMID:Retinoid receptors, transporters, and metabolizers as therapeutic targets in late onset Alzheimer disease. 1700 93

Studies in mice suggest that adipocytes serve as glucose sensors and regulate systemic glucose metabolism through release of serum retinol-binding protein 4 (RBP4). This model has not been validated in humans. RBP4 was highly expressed in isolated mature human adipocytes and secreted by differentiating human adipocytes. In contrast to the animal data, RBP4 mRNA was downregulated in subcutaneous adipose tissue of obese women, and circulating RBP4 concentrations were similar in normal weight, overweight, and obese women (n = 74). RBP4 was positively correlated with GLUT4 expression in adipose tissue, independent of any obesity-associated variable. Five percent weight loss slightly decreased adipose RBP4 expression but did not influence circulating RBP4. In another set of experiments, we stratified patients (n = 14) by low or high basal fasting interstitial glucose concentrations, as determined by the microdialysis technique. Venous glucose concentrations were similar throughout oral glucose tolerance testing, and basal RBP4 expression in adipose tissue and serum RBP4 concentrations were similar in the groups with higher and lower interstitial glucose levels. Our findings point to profound differences between rodents and humans in the regulation of adipose or circulating RBP4 and challenge the notion that glucose uptake by adipocytes has a dominant role in the regulation of RBP4.
Diabetes 2006 Oct
PMID:Retinol-binding protein 4 in human obesity. 1700 46

Thiazolidinediones (TZD) may improve insulin resistance in patients with diabetes and HIV. The novel adipocytokines visfatin and retinol-binding protein-4 (RBP-4) have been proposed to influence the development of impaired glucose tolerance. The impact of TZD on these cytokines is yet unknown. In this randomized, double-blind, placebo-controlled parallel group study, 37 lean HIV-positive subjects aged 19-50 years were treated with 8 mg/day rosiglitazone (n=20) or placebo (n=17) for 6 months. Insulin sensitivity was estimated from the homeostasis model assessment (HOMA) index. Fasting visfatin, RBP-4, leptin, and adiponectin plasma concentrations were analyzed by immunoassays. Rosiglitazone had no effect on impaired insulin sensitivity, but increased median plasma visfatin from 6.2 ng/ml (95% CI: 5.9; 6.5) to 13.7 ng/ml (12.6; 19.1) (P<0.001) and adiponectin from 3.2 ng/ml (2.2; 4.0) to 4.0 ng/ml (3.3; 8.5; P<0.001). RBP-4 was lowered from 21.0 ng/ml (19.6; 23.1) to 16.3 ng/ml (15.2; 17.0; P<0.001), and leptin concentrations were unchanged. Adipocytokine concentrations were stable in subjects receiving placebo, where a deterioration in insulin sensitivity was detectable (P<0.05). Changes in visfatin and RBP-4 were correlated in subjects receiving rosiglitazone (r=-0.64, P<0.01) but not placebo (r=0.12, P=0.15). TZD treatment affects circulating adipocytokine concentrations in subjects with HIV. Reductions in RBP-4 and increases in visfatin may contribute to the pharmacodynamic action of TZD on glucose homeostasis. Quantification of adipocytokines might be useful to assess TZD treatment effectiveness in insulin-resistant subjects with HIV.
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PMID:Effect of rosiglitazone on visfatin and retinol-binding protein-4 plasma concentrations in HIV-positive patients. 1723 34

Type 1 diabetes is associated with the presence of inflammation, which in turn affects parameters used to assess the vitamin A status. In the present study, we evaluated the influence of inflammatory status on retinol, retinol-binding protein 4 (RBP4), and transthyretin (TTR) in children and adolescents with type 1 diabetes. A total of 40 children with type 1 diabetes (median age, 14.2 y; median BMI-SDS, 0.53; median diabetes duration, 5.8 y; median HbA1c, 7.3%) and 46 healthy subjects (median age, 12.8 y; median BMI-SDS, 0.34; median HbA1c 5.4%) were recruited. Serum levels of CRP were significantly elevated (p = 0.005) and retinol concentrations were significantly lower (p = 0.02) in children and adolescents with type 1 diabetes compared with healthy subjects. Serum RBP4 and TTR showed no differences between the groups. Healthy children with CRP levels above 0.6 mg/L had significant lower levels of retinol (p = 0.03). This was not observed in children with type 1 diabetes. The results suggest that, in contrast to healthy children, minor CRP elevation does not affect vitamin A transport complex in serum of children with type 1 diabetes.
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PMID:High-normal C-reactive protein levels do not affect the vitamin A transport complex in serum of children and adolescents with type 1 diabetes. 1795 46

To assess whether plasma retinol-binding protein (RBP) is a marker of insulin resistance we measured RBP, insulin and glucose in 285 fasting subjects attending a Lipid Disorders Clinic as outpatients. They were grouped as either subjects without diabetes mellitus and with varying degrees of insulin resistance or subjects with diabetes mellitus according to the WHO criteria. We show that there was no association between plasma RBP and insulin-resistance, insulin, glucose, % body fat, waist circumference or BMI whether analysed together or in groups. We confirm, using the largest study cohort to date, that plasma RBP is unlikely to be a useful marker of insulin resistance.
Diabetes Res Clin Pract 2008 Apr
PMID:Plasma retinol-binding protein is unlikely to be a useful marker of insulin resistance. 1819 20

Adipose tissue is the source of soluble mediators (adipokines), secreted mainly by adipocytes. Leptin acts on the brain and peripheral organs to regulate energy homeostasis and the neuroendocrine axis. Adiponectin regulates glucose and lipid metabolism by targeting the liver and skeletal muscle. Adiposederived proinflammatory cytokines, vasoactive peptides, coagulation and complement factors, visfatin, vaspin and retinol-binding protein signal through paracrine and hormonal mechanisms. Understanding the biology of adipose tissue and the rapidly growing list of adipokines provides new insights into normal physiological regulation, as well as the pathogenesis and treatment of obesity, diabetes and disorders of lipid metabolism and cardiovascular system.
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PMID:Adipokines in obesity. 1823 Sep 3

Elevated C-reactive protein (CRP), IL-6 and retinol-binding protein 4 (RBP4) levels are associated with insulin resistance and diabetes mellitus. Phytoestrogens (including lignans and isoflavones) may enhance the management of diabetes and are hypothesized to act through inflammation pathways. The present study explored the effects of flaxseed-derived lignan on inflammatory factors and RBP4 concentrations in type 2 diabetics, who have higher levels of these biomarkers. Seventy community-dwelling diabetic patients (twenty-six men and forty-four post-menopausal women) with mild hypercholesterolaemia completed a randomized, double-blind, placebo-controlled, cross-over trial of supplementation with flaxseed-derived lignan capsules (360 mg/d) or placebo for 12 weeks, separated by an 8-week wash-out period. The participants maintained their habitual diets and levels of physical activity. Baseline to follow-up concentrations of CRP increased significantly within the placebo group (1.42 (sem 0.19) v. 1.96 (sem 0.22) mg/l, P < 0.001), but were comparatively unchanged in the lignan-supplemented group (1.67 (sem 0.19) v. 1.90 (sem 0.26) mg/l, P = 0.94); a significant difference was observed between treatments ( - 0.45 (95 % CI - 0.76, - 0.08) mg/l, P = 0.021). This effect was confined to women (P = 0.016), but not observed in men (P = 0.49). No between-treatment differences were found with regard to IL-6 or RBP4; though IL-6 concentrations increased significantly from baseline to follow-up in both groups (P = 0.004 and P < 0.001 following lignan and placebo treatments, respectively). The study suggests that lignan might modulate CRP levels in type 2 diabetics. These results need to be confirmed by further large clinical trials of longer duration.
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PMID:Effects of a flaxseed-derived lignan supplement on C-reactive protein, IL-6 and retinol-binding protein 4 in type 2 diabetic patients. 1877

Urotensin II (UII) was identified as the ligand for a novel G protein-coupled receptor, GPR14. UII was found not only to have a potent vasoconstrictive action but also to have profibrotic effects in the heart. The present study was to define whether UII and GPR14 also play important roles in diabetes-induced renal fibrosis and dysfunction. Diabetic rats were induced using streptozotocin, and the rat proximal tubular epithelial cells (NRK-52E) were used for the in vitro mechanism study. Results showed that expression of UII and GPR14 was significantly upregulated at both mRNA and protein levels in the diabetic kidneys compared with controls. The upregulated expressions of UII and GPR14 in the kidney were accompanied by significant increases in the renal profibrotic factor transforming growth factor (TGF)-beta1 expression, the renal extracellular matrix (fibronectin and collagen IV) accumulation, and the renal dysfunction (increases in urinal N-acetyl-beta-d-glucosaminidase content, 24-h urinary retinol-binding protein excretion rate, and decrease in creatinine clearance rate). Exposure of NRK-52E cells to 10(-8) mol/l UII for 48 h caused a significant increase of TGF-beta1, but not ANG II, production that was GPR14- and calcium-dependent, since GPR14 small-interfering RNA and calcium channel blocker nimodipine or calcium chelator EDTA all could abolish the induction of TGF- beta1 by UII. Furthermore, exposure of NRK-52E cells to TGF-beta1 or ANG II also increased UII and GPR14 mRNA expressions. These results suggested that diabetes-induced upregulation of UII and GPR14, most likely through autocrine and/or paracrine mechanisms, plays an important role in TGF-beta1-mediated renal fibrosis and dysfunction.
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PMID:Diabetes-induced upregulation of urotensin II and its receptor plays an important role in TGF-beta1-mediated renal fibrosis and dysfunction. 1879 44

In this randomized, placebo-controlled, double-blind study of 57 abdominally obese middle-aged men, conjugated linoleic acid (CLA) did not induce changes in retinol-binding protein 4 concentrations (RBP4), despite marked induced insulin resistance. Further, there were no associations between CLA-induced insulin resistance and changes in RBP4.
Diabetes Res Clin Pract 2008 Dec
PMID:Effects of trans10cis12CLA-induced insulin resistance on retinol-binding protein 4 concentrations in abdominally obese men. 1898 Jul 83

The prevalence of obesity among children and adolescents is progressively increasing around the world. One of the important consequences of obesity is the development of insulin resistance (IR). This condition has a multifactorial pathogenesis and is associated with cardiovascular risk, diabetes, hypertension, polycystic-ovary syndrome and a shorter lifespan. IR during childhood may be diagnosed by physical examination or there may be clues in the histories of the patient and his/her family. When IR is suspected, tests on a blood sample (which are more reliable) are recommended. Most of the biochemical markers have been well defined in adults, but appropriate reference data for children are still lacking. Here we discuss the usefulness of various currently known biochemical markers to evaluate insulin sensitivity (homeostatic model assessment, the quantitative insulin sensitivity check index, the oral glucose tolerance test, Matsuda method and the whole-body insulin resistance index), hormones (leptin, adiponectin, resistin, glucocorticoids, the insulin-like growth factor-1-binding protein/growth hormone axis, ghrelin, sex hormone-binding globulin and retinol-binding protein-4) and inflammatory markers (C-reactive protein, IL-6, intercellular adhesion molecule-1, vascular adhesion molecule-1 and E-selectin), which can be used in the diagnosis of IR in children.
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PMID:Insulin resistance markers in children. 1912 10


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