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)

The aim of this study was to investigate the relationships among insulin resistance and albumin excretion rate in 25 nondiabetic patients with essential hypertension and in 28 patients with non-insulin dependent diabetes mellitus (NIDDM). Two groups of healthy subjects matched for age, sex, and weight served as controls. Patients with essential hypertension were divided into two subgroups: without (H1) and with (H2) microalbuminuria. Diabetic patients were divided into four subgroups: those with normoalbuminuria without (NIDDM1) and with (NIDDM2) hypertension and those with microalbuminuria without (NIDDM3) and with (NIDDM4) hypertension. Whole-body glucose utilization during euglycemic hyperinsulinemic clamp (40 mU/m2/min insulin infusion) was calculated by tracer dilution techniques (6,6 2H2 glucose tracer continuous infusion) and was significantly lower in hypertensives with microalbuminuria than in those without (H2 versus H1 versus controls: 3.41 +/- 0.51 versus 6.52 +/- 0.62 versus 7.03 +/- 0.48 mg/kg/min; mean +/- SE). Whole-body glucose utilization in NIDDM patients--NIDDM4 versus NIDDM3 versus NIDDM2 versus NIDDM1 versus controls--was: 1.86 +/- 0.31 versus 2.21 +/- 0.39 versus 2.01 +/- 0.40 versus 5.98 +/- 0.77 versus 5.52 +/- 0.92 mg/kg/min (mean +/- SE). Whereas the first three subgroups did not differ among themselves, they had significantly lower glucose utilization than did the normotensive NIDDM1 patients without microalbuminuria and nondiabetic controls (P < 0.01). Hypertensives with microalbuminuria had higher Vmax of sodium-lithium countertransport (Na/Li CTT) in red blood cells than did both hypertensives without microalbuminuria and controls. It was also observed that NIDDM patients with microalbuminuria had higher Vmax of Na/Li CTT than did NIDDM patients without microalbuminuria and controls.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Close relationship between microalbuminuria and insulin resistance in essential hypertension and non-insulin dependent diabetes mellitus. 145 61

Non-insulin-dependent (type 2) diabetes mellitus (NIDDM) is a common disorder of middle-aged individuals characterized by high blood glucose levels which, if untreated, can cause serious medical complications and lead to early death. Genetic factors play an important role in determining susceptibility to this disorder. However, the number of genes involved, their chromosomal location and the magnitude of their effect on NIDDM susceptibility are unknown. We have screened the human genome for susceptibility genes for NIDDM using non-and quasi-parametric linkage analysis methods in a group of Mexican American affected sib pairs. One marker, D2S125, showed significant evidence of linkage to NIDDM and appears to be a major factor affecting the development of diabetes mellitus in Mexican Americans. We propose that this locus be designated NIDDM1.
 ...
PMID:A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2. 932 32

Complex disorders such as diabetes, cardiovascular disease, asthma, hypertension and psychiatric illnesses account for a large and disproportionate share of health care costs, but remain poorly characterized with respect to aetiology. The transmission of such disorders is complex, reflecting the actions and interactions of multiple genetic and environmental factors. Genetic analyses that allow for the simultaneous consideration of susceptibility from multiple regions may improve the ability to map genes for complex disorders, but such analyses are currently computationally intensive and narrowly focused. We describe here an approach to assessing the evidence for statistical interactions between unlinked regions that allows multipoint allele-sharing analysis to take the evidence for linkage at one region into account in assessing the evidence for linkage over the rest of the genome. Using this method, we show that the interaction of genes on chromosomes 2 (NIDDM1) and 15 (near CYP19) makes a contribution to susceptibility to type 2 diabetes in Mexican Americans from Starr County, Texas.
 ...
PMID:Loci on chromosomes 2 (NIDDM1) and 15 interact to increase susceptibility to diabetes in Mexican Americans. 998 76

Recent advancement of molecular biology highlighted three areas of basic research which may be important for clinical diabetology. One is the understanding of mechanisms of differentiation in pancreatic beta-cells and adipocytes. The second is the development of methods of tissue-specific knock-out mouse. This approach revealed that muscle may not be important for insulin-dependent glucose disposal in vivo. The third is the advancement of genetics which enabled to clone a major susceptibililly gene for type 2 diabetes mellitus (NIDDM1). These progress may bring new therapies for clinical diabetology.
 ...
PMID:[Molecular biology and clinical diabetology]. 1019 24

Type 2 or non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes worldwide, affecting approximately 4% of the world's adult population. It is multifactorial in origin with both genetic and environmental factors contributing to its development. A genome-wide screen for type 2 diabetes genes carried out in Mexican Americans localized a susceptibility gene, designated NIDDM1, to chromosome 2. Here we describe the positional cloning of a gene located in the NIDDM1 region that shows association with type 2 diabetes in Mexican Americans and a Northern European population from the Botnia region of Finland. This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). This finding suggests a novel pathway that may contribute to the development of type 2 diabetes.
 ...
PMID:Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. 1101 62

Previous linkage studies in Mexican-Americans localized a major susceptibility locus for type 2 diabetes, NIDDM1, to chromosome 2q. This evidence for linkage to type 2 diabetes was recently found to be associated with a common G-->A polymorphism (UCSNP-43) within the CAPN10 gene. The at-risk genotype was homozygous for the UCSNP-43 G allele. In the present study among Pima Indians, the UCSNP-43 G/G genotype was not associated with an increased prevalence of type 2 diabetes. However, Pima Indians with normal glucose tolerance, who have a G/G genotype at UCSNP-43, were found to have decreased rates of postabsorptive and insulin-stimulated glucose turnover that appear to result from decreased rates of glucose oxidation. In addition, G/G homozygotes were found to have reduced CAPN10 mRNA expression in their skeletal muscle. A decreased rate of insulin-mediated glucose turnover, or insulin resistance, is one mechanism by which the polymorphism in CAPN10 may increase susceptibility to type 2 diabetes mellitus in older persons.
 ...
PMID:A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance. 1101 67

Several topics in diabetes research and practice in the coming 'post-genomic era' are described. 1) Insulin-producing pancreatic beta cells are a plausible target of gene therapy for type 1 diabetes mellitus. Functional genomics will reveal the mechanism of beta cell growth and regeneration. Attempts are being made to differentiate non-beta cells(including ES cells) into insulin-producing cells in vitro or in vivo. 2) Very recently, an intron variation in calpain 10 gene was found to be associated with type 2 diabetes, which confirmed the importance of SNPs in common diseases. More and more SNPs related to type 2 diabetes will be discovered and, in combination with pharmacogenomics, 'personalized medicine' based on SNP information of the individuals will hopefully be achieved.
 ...
PMID:[Perspectives on postgenome medicine: Gene therapy for diabetes mellitus]. 1119 48

Type 2 diabetes is a multifactorial disease composed of subtypes strongly associated with environmental factors at one end of the spectrum and highly genetic forms at the other hand. The former forms have been largely elucidated in the last years by the identification of the 5 genes responsible for the autosomal dominant MODY subtype: glucokinase, and 4 transcription factors which play a key role in the development of the endocrine pancreas or in the expression of glucose metabolism genes. Apart from the monogenic forms of type 2 diabetes little is known about the nature of the genetic factors involved. Minor contributors include insulin, sulfamide receptor and some others. Genome scans of diabetic families have revealed susceptibility loci on chromosome 1q, 2p, 2q (where the gene calpain 10 was recently cloned), 3q, 12q and 20. The identification of diabetes susceptibility gene is the first step to define targets of new drugs against diabetes.
 ...
PMID:[Genetics of type II diabetes]. 1129 66

Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both. Genetic factors contribute to the development of diabetes. Some forms such as the condition called maturity-onset diabetes of the young(MODY) result from mutations in a single gene. Other forms such as type 1 or type 2 diabetes are multifactorial in origin with different combinations of genes together with non-genetic factors contributing to the development of hyperglycemia. MODY has been a good model for studying the genetics and pathophysiology of diabetes. This form of diabetes can result from mutations in at least seven different genes: hepatocyte nuclear factor(HNF)-4 alpha/MODY1, glucokinase/MODY2, HNF-1 alpha/MODY3, insulin promoter factor(IPF-1)/MODY4, HNF-1 beta/MODY5, NeuroD1/MODY6 and Islet(Isl)-1/MODY7. Mutations in HNF-1 alpha/MODY3 are the most common cause of MODY in Japanese identified to date accounting for about 15% of cases of MODY. Mutations in the HNF-4 alpha/MODY1, glucokinase/MODY2, HNF-1 beta/MODY5 and Isl-1/MODY7 genes have also been found in Japanese; however, they are rare causes of MODY. Clinical studies indicate that patients with MODY are generally not obese and that all forms of MODY are characterized by pancreatic beta-cell dysfunction. Patients who have mutations in the HNF-1 beta/MODY5 gene have non-diabetic kidney dysfunction including renal cysts. Female carriers may also exhibit abnormalities in the upper vagina and uterus. Genetic approach for type 2 diabetes had done by using non-parameteric linkage analysis such as sibpair analysis which worked well and NIDDM1 and NIDDM2 have been identified to date. The responsible gene for NIDDM1 was recently identified to be Calpain 10, and SNP43 in this gene could explain all of the evidence for linkage in Mexican American type 2 diabetes.
 ...
PMID:[Diabetes mellitus]. 1130 9

Calpains are calcium-dependent intracellular nonlysosomal proteases that are believed to hydrolyze specific substrates important in calcium-regulated signaling pathways. Recently, an atypical member of the calpain family, calpain 10, was described, and genetic variation in this gene was associated with an increased risk of type II diabetes mellitus in humans. In the present report, a polyclonal antibody directed against rat calpain 10 was developed. This antibody was used to monitor the expression of calpain 10 protein in tissues from rats, mice, and humans. Calpain 10 protein was found to be present in all tissues examined by Western blotting including the lens, retina, brain, heart, and skeletal muscle. Although some calpain 10 was detectable in the water-soluble protein fraction of these tissues, it was preferentially found in the water-insoluble fraction. In the lens, immunohistochemistry revealed that calpain 10 was predominately located in the cytoplasm of epithelial and newly differentiating lens fibers at the transition zone. However, calpain 10 was found to be associated with the plasma membrane of differentiated lens fiber cells and the sarcolemma of skeletal muscle. In the lens epithelium-derived cell line, alphaTN4-1, the calpain 10 protein was found in a punctate distribution in the cell nucleus as well as the cytoplasm. After the elevation of intracellular calcium levels with ionomycin, calpain 10 protein levels in the nucleus of alphaTN4-1 cells increased markedly, whereas those in the cytoplasm decreased. In the lens, the elevation of intracellular calcium levels after selenite administration resulted in increased levels of calpain 10 RNA within 1 day and a loss of calpain 10 protein from the lens nucleus coincident with the onset of selenite cataract. In conclusion, calpain 10 seems to be a ubiquitous calpain, the expression level and subcellular distribution of which are dynamically influenced by calcium.
 ...
PMID:Characterization and expression of calpain 10. A novel ubiquitous calpain with nuclear localization. 1137 82


1 2 3 4 5 6 Next >>