Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Otsuka Long-Evans Tokushima fatty (OLETF) rat is an animal model of type 2 diabetes, characterized by abdominal obesity, insulin resistance, hypertension, and dyslipidemia. To elucidate the underlying molecular mechanism of obesity and its related complications, we used representational difference analysis and identified the genes more abundantly and specifically expressed in the visceral adipose tissue (VAT) of obese OLETF rats compared with the diabetes-resistant counterpart, that is, Long-Evans Tokushima Otsuka (LETO) rats. By Northern blot analysis, we confirmed the differential expression of 13 genes, including 3 novel genes. The upregulated expression of well-characterized lipid metabolic enzymes, such as lipoprotein lipase, phosphoenolpyruvate carboxykinase, and cholesterol esterase, were observed in VAT of OLETF rats. We demonstrated the differential expression of secreted proteins in VAT of OLETF rats, such as thrombospondin 1 and contrapsin-like protease inhibitor. In contrast to lipid enzymes, the secreted proteins revealed exclusive mRNA expression and they were not detected in VAT of LETO rats. Furthermore, the novel genes OL-16 and OL-64 were also expressed specifically in VAT of OLETF rats and were absent in that of LETO rats and other tissues, including subdermal and brown adipose tissues. The C-terminal partial amino acid sequence of OL-64 revealed that it showed approximately 40% homology with alpha(1)-antitrypsin and it seemed to be a new member of the serine proteinase inhibitor (SERPIN) gene family. VAT of OLEFT rats had a unique gene expression profile, and the accumulated VAT-specific known and novel secreted proteins may play a role(s) in the pathogenesis of obesity and its related complications.
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PMID:Identification of genes specifically expressed in the accumulated visceral adipose tissue of OLETF rats. 1101 3

There is a rapid global rise in obesity, and the link between obesity and diabetes remains somewhat obscure. We identified an adipocytokine, designated as visceral adipose tissue-derived serpin (vaspin), which is a member of serine protease inhibitor family. Vaspin cDNA was isolated by from visceral white adipose tissues (WATs) of Otsuka Long-Evans Tokushima fatty (OLETF) rat, an animal model of abdominal obesity with type 2 diabetes. Rat, mouse, and human vaspins are made up of 392, 394, and 395 amino acids, respectively; exhibit approximately 40% homology with alpha1-antitrypsin; and are related to serine protease inhibitor family. Vaspin was barely detectable in rats at 6 wk and was highly expressed in adipocytes of visceral WATs at 30 wk, the age when obesity, body weight, and insulin levels peak in OLETF rats. The tissue expression of vaspin and its serum levels decrease with worsening of diabetes and body weight loss at 50 wk. The expression and serum levels were normalized with the treatment of insulin or insulin-sensitizing agent, pioglitazone, in OLETF rats. Administration of vaspin to obese CRL:CD-1 (ICR) (ICR) mice fed with high-fat high-sucrose chow improved glucose tolerance and insulin sensitivity reflected by normalized serum glucose levels. It also led to the reversal of altered expression of genes relevant to insulin resistance, e.g., leptin, resistin, TNFalpha, glucose transporter-4, and adiponectin. In DNA chip analyses, vaspin treatment resulted in the reversal of expression in approximately 50% of the high-fat high-sucrose-induced genes in WATs. These findings indicate that vaspin exerts an insulin-sensitizing effect targeted toward WATs in states of obesity.
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PMID:Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity. 1603 Jan 42

Few Type 2 diabetes loci are considered confirmed and replicated across multiple populations. Some genes that have become accepted as contributors to diabetes risk include: calpain 10, peroxisome proliferator-activated receptor-gamma, ATP-sensitive inwardly rectifying potassium channel subunit Kir6.2, hepatocyte nuclear factor 4alpha and hepatic transcription factor 1. While numerous reports of new diabetes loci enter the literature on a regular basis, this review focuses on selected novel associations reported within the last 12 months. In particular, we highlight recent reports of associations between Type 2 diabetes and the transcription factor 7-like 2 gene, associations with micro-opioid receptor and supressor of cytokine signaling 2 genes, and expression and functional analyses of adipokines vaspin and retinol binding protein 4. These new results provide insights into possible mechanisms influencing disease susceptibility and thus new diagnostic and therapeutic opportunities for Type 2 diabetes.
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PMID:Genetic contributions to type 2 diabetes: recent insights. 1733 Oct 67

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

Vaspin has recently been identified as novel adipokine with high expression in adipose tissue of obese and type 2 diabetic subjects and with potentially insulin-sensitising properties. However, the impact of vaspin gene variants on the risk of type 2 diabetes mellitus (T2DM) has not been determined yet. Therefore, the aim of our study was to investigate the association of vaspin single nucleotide polymorphisms (SNPs) with T2DM and obesity. We analysed the association between 25 vaspin SNPs and T2DM in initially healthy 35-84 year-old individuals of the population-based, cross-sectional German KORA F3 study and assessed the association with measures of obesity. Genotyping was carried out with matrix-assisted laser desorption/ionisation-time of flight mass spectrometry of allele-dependent primer extension products and associations with T2DM and obesity were analysed by logistic regression analysis. Our results demonstrate a significant association of vaspin SNP rs2236242 with T2DM in the KORA F3 study with the AA genotype bearing an increased risk (adjusted OR 2.35 [1.59; 3.46] versus AT/TT). This association appears to be independent of obesity. Our finding corroborates previous studies that suggested a link between the novel adipokine vaspin and glucose metabolism.
Exp Clin Endocrinol Diabetes 2010 Mar
PMID:Vaspin (SERPINA12) genotypes and risk of type 2 diabetes: Results from the MONICA/KORA studies. 1872 71

We have identified the vaspin gene(serpina12), which is up-regulated in visceral white adipose tissues (WATs) of Otsuka Long-Evans Tokushima fatty (OLETF) rat, an animal model of abdominal obesity and type 2 diabetes. Vaspin mRNA was barely detectable at 6 weeks of age, but was abundantly and exclusively expressed in visceral WATs at 30 weeks of age, when OLETF rats reach their peak body weight. However, vaspin mRNA decreased with worsening of diabetes and body weight loss. Vaspin mRNA increased with administration of thiazolidinediones, i.e. pioglitazone. Administration of recombinant vaspin into high fat high sucrose (HFHS) chow-induced obese ICR mice improved glucose tolerance and insulin sensitivity. Vaspin may be the compensatory molecule in the pathogenesis of metabolic syndrome and vaspin recombinant protein or vaspin-mimicking agents such as vaspin analogues, antibodies or small molecule agents would link to drug discovery and development.
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PMID:[Vaspin and insulin resistance]. 1880 Jun 27

Diabetes is an important health problem since the incidence of diabetes is continuously increasing. Early diagnosis is important as type 2 diabetes begins long before we diagnose it, leading to a complicated course of the disease. In order to prevent delay in the diagnosis of type 2 diabetes, novel predictors and pathways for type 2 diabetes are mounting. Diabetic complications are common cause of morbidity and mortality among subjects with diabetes. In the pathogenesis of diabetic complications some factors other than chronic hyperglycemia may be involved. Adipocytokines play important roles in the pathogenesis of diabetes mellitus, insulin resistance, and associated metabolic conditions such as hypertension and dyslipidemia. The investigations on the role of adipocytokines in developing diabetes and its complications have been made. In this review, we discussed the implications of adipocytokines in predicting diabetes and diabetic complications, with particular attention on the roles of adiponectin, leptin, visfatin, and vaspin.
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PMID:Role of adipocytokines in predicting the development of diabetes and its late complications. 1977 67

Adipocytokine profile seems to play a distinct role in the pathogenesis of chronic hepatitis C (CHC). Chemerin and vaspin are recently described adipocytokines with various suggested functions and potential to modulate inflammatory response and insulin resistance (IR). We assessed chemerin, vaspin and leptin serum concentration and studied their association with IR laboratory and morphological features in patients with hepatitis C. The study included 40 patients with hepatitis C and 20 healthy volunteers, similar in age and body mass index (43.6 +/- 11.6 vs 40.9 +/- 11.8 years and 25.0 +/- 4.1 vs 23.9 +/- 3.3 kg/m(2), respectively). Patients had to have a normal lipid profile, and diabetes was an exclusion criteria. Serum chemerin and leptin levels and IR were significantly higher in patients with hepatitis C when compared to the controls (P = 0.02, P = 0.02 and P = 0.02, respectively), whereas vaspin level was significantly decreased (P = 0.01). Serum chemerin was negatively associated with necro-inflammatory grade (r = (-0.49), P = 0.01). The lowest levels of serum chemerin were found in patients with moderate/severe inflammation (P = 0.03). Serum leptin tended to be up-regulated in patients with minimal inflammatory activity. Serum vaspin was higher, although not significantly, when fibrosis was more advanced. IR was positively associated with fibrosis stage (r = 0.33, P = 0.03). Serum chemerin and leptin were related to each other (r = 0.45, P = 0.02).Our findings support a complex interaction between the analysed adipokines and pathogenesis of inflammatory process in CHC. The role of chemerin and vaspin in pathogenesis of inflammatory response should be further investigated.
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PMID:Chemerin, vaspin and insulin resistance in chronic hepatitis C. 2000 64

The aim of this study is to compare the effects of candesartan and olmesartan on insulin sensitivity-related parameters, before and after antihypertensive therapy. After a 4-week washout placebo period, 194 hypertensive (diastolic blood pressure (DBP) > or =80 mm Hg and systolic blood pressure (SBP) > or =130 mm Hg) patients with well-controlled type II diabetes were randomized to receive either 8 mg of candesartan once a day (o.d.) or 10 mg olmesartan o.d. and titrated after 1 month to 16 mg candesartan o.d. or 20 mg olmesartan o.d., respectively; the treatment period had a 1-year duration. We evaluated body weight, body mass index, SBP, DBP, glycated hemoglobin, fasting plasma glucose, M value, adiponectin (ADN), resistin (r), retinol-binding protein 4, visfatin, vaspin and high-sensitivity C-reactive protein (Hs-CRP) at their baseline values and after 6 and 12 months of treatment. We observed no variation in body weight or glycemic profile for either treatment. SBP and DBP were significantly reduced by both treatments (from 144+/-8/88+/-6 to 126+/-5/77+/-4 mm Hg by candesartan (P<0.001) and from 145+/-9/89+/-7 to 128+/-7/79+/-5 mm Hg by olmesartan (P<0.001)) without any difference between them. Retinol binding protein-4, r, and the vaspin value decreased in the candesartan group but not in olmesartan group. The M value, visfatin and ADN increased with candesartan, whereas no significant variations were observed with olmesartan. Both treatments resulted in a similar reduction in Hs-CRP. Although both therapies resulted in similar reductions in blood pressure, candesartan therapy was more effective than olmesartan therapy in improving insulin sensitivity.
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PMID:Differential effects of candesartan and olmesartan on adipose tissue activity biomarkers in type II diabetic hypertensive patients. 2055 29

Adipose tissue is now regarded as an active endocrine organ which can secrete various cytokines. Adipocyte-derived cytokines are termed adipocytokines (adipocytes+cytokine). Adipocytokines can affect vascular systems to prevent or exacerbate obesity-related vascular complications, including diabetes-related vascular dysfunction, hypertension, and atherosclerosis. However, their basic vascular functions remain to be fully determined. In this manuscript, I summarize our recent findings on the vascular effects of 5 newly identified adipocytokines (omentin, visfatin, nesfatin, vaspin, and chemerin), with a special focus on 1) vascular contractile reactivity, and 2) vascular inflammatory response/injury. These novel adipocytokines may be important future targets for the development of drugs and therapy for treating metabolic vascular disorders.
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PMID:Vascular effects of novel adipocytokines: focus on vascular contractility and inflammatory responses. 2137 76


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