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)

Non-insulin-dependent diabetes mellitus (NIDDM) is a multifactoral disease with both environmental and genetics causes. Genome-wide screening procedures have identified several susceptibility loci for NIDDM within the human genome. We describe the cloning of a putative sugar transporter that has been localized to human chromosome 20q12-q13.1, one of the genomic loci associated with NIDDM. Because of the strong resemblance of this novel protein to members of the mammalian facilitative glucose transporter family (GLUT), we refer to the protein as GLUT10 (HGMW-approved gene symbol SLC2A10). GLUT10 contains 541 amino acids with several glucose transporter sequence motifs and amino acids essential for glucose transport function. In addition, secondary structure analysis of GLUT10 predicts 12 putative transmembrane domains, a hallmark structure of the GLUT family. The tissue distribution of GLUT10 was determined by Northern analysis, which revealed highest levels of expression in the liver and pancreas. From these data, we believe that the chromosomal localization, tissue distribution, and predicted function make GLUT10 an excellent candidate for a susceptibility gene involved in NIDDM.
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PMID:Molecular cloning of a novel member of the GLUT family of transporters, SLC2a10 (GLUT10), localized on chromosome 20q13.1: a candidate gene for NIDDM susceptibility. 1124 74

The SLC2A10 gene encodes the GLUT10 facilitative glucose transporter, which is expressed in high amounts in liver and pancreas. The gene is mapped to chromosome 20q12-q13.1, a region that has been shown to be linked to type 2 diabetes. The gene was examined in 61 Danish type 2 diabetic patients, and a total of six variants (-27C-->T, Ala206Thr, Ala272Ala, IVS2 + 10G-->A, IVS4 + 18T-->G, and IVS4 + 26G-->A) were identified and investigated in an association study, which included 503 type 2 diabetic patients and 510 glucose-tolerant control subjects. None of the variants were associated with type 2 diabetes. Interestingly, carriers of the codon 206 Thr allele had 18% lower fasting serum insulin levels (P = 0.002) and 20% lower insulinogenic index (P = 0.03) than homozygous carriers of the Ala allele. These results suggest that variation in the coding region of SLC2A10 does not contribute substantially to the pathogenesis of type 2 diabetes in the examined study population. However, the codon 206 polymorphism may be related to the interindividual variation in fasting and oral glucose-induced serum insulin levels.
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PMID:Genetic variation of the GLUT10 glucose transporter (SLC2A10) and relationships to type 2 diabetes and intermediary traits. 1294 88

Arterial tortuosity syndrome (ATS) is an autosomal recessive disorder characterized by tortuosity, elongation, stenosis and aneurysm formation in the major arteries owing to disruption of elastic fibers in the medial layer of the arterial wall. Previously, we used homozygosity mapping to map a candidate locus in a 4.1-Mb region on chromosome 20q13.1 (ref. 2). Here, we narrowed the candidate region to 1.2 Mb containing seven genes. Mutations in one of these genes, SLC2A10, encoding the facilitative glucose transporter GLUT10, were identified in six ATS families. GLUT10 deficiency is associated with upregulation of the TGFbeta pathway in the arterial wall, a finding also observed in Loeys-Dietz syndrome, in which aortic aneurysms associate with arterial tortuosity. The identification of a glucose transporter gene responsible for altered arterial morphogenesis is notable in light of the previously suggested link between GLUT10 and type 2 diabetes. Our data could provide new insight on the mechanisms causing microangiopathic changes associated with diabetes and suggest that therapeutic compounds intervening with TGFbeta signaling represent a new treatment strategy.
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PMID:Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. 1657 59

Heart consumes more energy than any other organ. It can utilize various metabolic substrates as a source of energy. The primary substrates are free fatty acids, especially long-chain fatty acids and glucose. The lipid bilayer of plasmalemma is impermeable for glucose. Therefore, glucose transport across the plasma membrane is mediated via glucose transporters. In human, cardiac cells are expressed as 2 families of glucose transporters: GLUTs and SGLTs. These transport proteins are GLUT1, GLUT3, GLUT8, GLUT10, GLUT11, GLUT12 and SGLT1. In human heart, GLUT4 is the major isoform that represents approximately 70% of the total glucose transporters. The changes observed in diabetic heart showed that type 1 diabetes mellitus alters the expression and translocation of GLUT4 and GLUT8 in the atria. In diabetic atria, the content in cell surface of these glucose transporters is downregulated. Expression of SGLT1, is increased in patients with end-stage cardiomyopathy secondary to type 2 diabetes. Increased expression of SGLT1 is a compensatory mechanism to the reduction in cardiac GLUT1 and GLUT4 expression. In animal model of type 1 diabetes, the expression of Sglt1 transporter is significantly decreased, and in the animal model of type 2 diabetes it is significantly increased. In heart diseases, such as cardiac hypertrophy (that is similar to fetal heart), heart failure and myocardial ischemia different perturbations in expression of glucose transporters are observed, especially in GLUT1 and GLUT4, due to changes in heart glucose metabolism. In this article, the functions of glucose transporters in healthy heart and in cardiac diseases are reviewed.
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PMID:Glucose transporters in healthy heart and in cardiac disease. 2803 63