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)

Skeletal muscle glycogen synthase (encoded by GYS1 on chromosome 19q13.3) is the rate-limiting enzyme in insulin-mediated non-oxidative glucose disposal. Our previous studies have demonstrated an impairment of insulin-stimulated GYS1 activities in insulin-resistant Pima Indians, and associations of non-insulin-dependent diabetes mellitus (NIDDM) with the GYS1 locus were reported recently in Finnish and Japanese populations. We have performed linkage and association analyses of GYS1 and seven additional DNA markers on 19q with NIDDM, and with parameters of insulin action in the Pima Indians. We have found a significant association of NIDDM with GYS1 genotypes (p = 0.009), and with common GYS1 alleles (p = 0.022) in the Pima Indians. We have performed a detailed comparative analysis of the GYS1 gene, mRNA, and protein product in insulin-sensitive and insulin-resistant Pima Indians. No mutations in GYS1 coding sequences were detected; nor did we find alterations of GYS1 mRNA expression or of its basal enzymatic activity in insulin-resistant Pima Indians. These results contrasted with a 25% reduction of immunoreactive protein in insulin-resistant subjects as detected by Western blotting with an antibody specific for the C-terminal end of GYS1 (t-test p = 0.024; Wilcoxon's rank-sum test, p = 0.04). Because no mutations were detected in the DNA encoding this epitope, the difference in immunoreactivity may reflect post-translational modification(s) of the protein rather than a difference in the gene itself, or it could have occurred by chance. We conclude that our data do not indicate alterations in the GYS1 gene as the cause for the observed association, and that a different locus near GYS1 may be the contributing genetic element.
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PMID:Association of the glycogen synthase locus on 19q13 with NIDDM in Pima Indians. 872 77

Impaired glycogen synthesis after insulin stimulation accounts for most of the insulin resistance in patients with non-insulin-dependent diabetes mellitus (NIDDM). The glycogen synthase gene (GYS1), which encodes the rate-limiting enzyme for glycogen synthesis, is a promising candidate gene for NIDDM. Therefore, we screened all 16 exons of this gene by single-strand conformation polymorphism analysis in 40 patients with NIDDM (age 67 +/- 2 years, body mass index 28.2 +/- 0.6 kg/m2) from Taipalsaari, eastern Finland. The Gly464Ser variant (exon 11) and a silent polymorphism TTC342TTT (exon 7) have been reported previously. In addition, we found a new variant Gln71His (exon 2) and a new amino acid polymorphism Met416Val (exon 10). An additional sample of 65 patients with NIDDM and 82 normoglycaemic men (age 54 +/- 1 years, body mass index 26.3 +/- 1.4 kg/m2) were screened. The allele frequency of the TTC342TTT silent substitution was 0.29 in both NIDDM and normoglycaemic subjects. The Gln71His and Gly464Ser variants were found in 1 (1%) and 3 (3%) subjects, respectively, of the 105 NIDDM patients and in none of the 82 normoglycaemic men. The Met416Val polymorphism was found in 16 (15%) of the 105 NIDDM patients and in 14 (17%) of the 82 control subjects (all heterozygous). The Met416Val polymorphism was not associated with insulin resistance in two groups of normoglycaemic subjects. In conclusion, the new Gln71His and Met416Val substitutions and other variants of the glycogen synthase gene are unlikely to make a major contribution to insulin resistance and NIDDM in diabetic patients from eastern Finland.
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PMID:New variants in the glycogen synthase gene (Gln71His, Met416Val) in patients with NIDDM from eastern Finland. 938 24

Associations between glycogen synthase gene (GYS1) polymorphism and states of insulin resistance and type 2 diabetes have been reported. The purpose of this study was to establish if the GYS1 genotype impacts on the content of glycogen synthase (GS) protein in muscle measured under basal and stimulated conditions. To examine this, GYS1 XbaI and Met416Val polymorphisms and thigh muscle GYS1 protein content were determined at rest, both before and after several weeks of neuromuscular electrical stimulation in carriers and noncarriers of the mutations. The allelic frequency was 0.086 for the XbaI mutation (A2) and 0.006 for the Met416Val in our cohort of French-Canadian subjects. When measured at rest, the GS protein content in muscle was similar among carriers and noncarriers of the XbaI variant. However, the stimulation-induced increase (23%) in the amount of GS muscle protein normally seen in wildtype individuals was impaired in those carrying the XbaI mutation. These data demonstrate that some individuals, because of their genetic background, are unable to stimulate the process of GS protein accumulation in skeletal muscle. These results could explain why some individuals appear to be genetically predisposed to developing skeletal muscle insulin resistance when exposed to unfavorable metabolic environments.
Diabetes 2001 Jan
PMID:The stimulation-induced increase in skeletal muscle glycogen synthase content is impaired in carriers of the glycogen synthase XbaI gene polymorphism. 1114 87

Glycogen is an important component of whole-body glucose metabolism. MGSKO mice lack skeletal muscle glycogen due to disruption of the GYS1 gene, which encodes muscle glycogen synthase. MGSKO mice were 5-10% smaller than wild-type littermates with less body fat. They have more oxidative muscle fibers and, based on the activation state of AMP-activated protein kinase, more capacity to oxidize fatty acids. Blood glucose in fed and fasted MGSKO mice was comparable to wild-type littermates. Serum insulin was lower in fed but not in fasted MGSKO animals. In a glucose tolerance test, MGSKO mice disposed of glucose more effectively than wild-type animals and had a more sustained elevation of serum insulin. This result was not explained by increased conversion to serum lactate or by enhanced storage of glucose in the liver. However, glucose infusion rate in a euglycemic-hyperinsulinemic clamp was normal in MGSKO mice despite diminished muscle glucose uptake. During the clamp, MGSKO animals accumulated significantly higher levels of liver glycogen as compared with wild-type littermates. Although disruption of the GYS1 gene negatively affects muscle glucose uptake, overall glucose tolerance is actually improved, possibly because of a role for GYS1 in tissues other than muscle.
Diabetes 2005 Dec
PMID:Glucose metabolism in mice lacking muscle glycogen synthase. 1630 63

We previously selected a group of hypertension candidate genes by a key word search using the OMIM database of NCBI and validated 525 coding single nucleotide polymorphisms (SNPs) in 179 hypertension candidate genes by DNA sequencing in a Japanese population. In the present study, we examined the association between 61 non-synonymous SNPs and blood pressure variations and hypertension. We used DNA samples taken from 1,880 subjects in the Suita study, a population-based study using randomly selected subjects. Analyses of covariance adjusting for age, body mass index, hyperlipidemia, diabetes, smoking, drinking, and antihypertensive medication revealed that 17 polymorphisms in 16 genes (APOB, CAST, CLCNKB, CTNS, GHR, GYS1, HF1, IKBKAP, KCNJ11, LIPC, LPL, P2RY2, PON2, SLC4A1, TRH, VWF) were significantly associated with blood pressure variations. Multivariate logistic regression analysis with adjustment for the same factors revealed that 11 polymorphisms in 11 genes (CAST, CTLA4, F5, GC, GHR, LIPC, PLA2G7, SLC4A1, SLCI8A1, TRH, VWF) showed significant associations with hypertension. Five polymorphisms in five genes, CAST(calpastatin), LIPC (hepatic lipase), SLC4A1 (band 3 anion transporter), TRH (thyrotropin-releasing hormone), and VWF (von Willebrand factor), were significantly associated with both blood pressure variation and hypertension. Thus, our study suggests that these five genes were susceptibility genes for essential hypertension in this Japanese population.
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PMID:Association of sixty-one non-synonymous polymorphisms in forty-one hypertension candidate genes with blood pressure variation and hypertension. 1713 17

Type 2 diabetes (T2D) with high morbidity and mortality is characterized by abnormal glucose and lipid metabolism due in part to insulin resistance in liver, which lead to elevated hyperglycemia and hyperlipidemia. This study sough to explore the effects of corosolic acid (CA) in different T2D models and explored the underlying mechanism. Separated from Eriobotrya japonica leaves, CA purity was above 95% measured by a HPLC method. Compared with cAMP and DEX induced T2D HepG2 model, CA significantly stimulated glucose consumption and improved glycogen accumulation by inhibiting PEPCK mRNA expression. And in cAMP and DEX induced T2D zebrafish model, CA reduced glycogen degradation and increased glucose consumption by regulating some key enzymes in carbon metabolism including GLUT1, GLUT2, GLUT3, LDHA, LDHB, GP, G6Pase, GYS1, and PFKFB3. In addition, insulin receptor signals were also involved in CA-regulated hypoglycemic action. Furthermore, in STZ-induced T2D rat model, compared with diabetic control groups, CA remarkably downregulated the levels of serum lipid, blood glucose, ICAM-1, malonaldehyde and insulin resistance index, while upregulated SOD activity and impaired glucose tolerance. In a conclusion, CA can regulate glucose and lipid metabolic adaptation in T2D like HepG2, zebrafish and rat models partly through reducing inflammation and oxidative stress and suppressing PEPCK.
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PMID:Corosolic acid isolated from Eriobotrya japonica leaves reduces glucose level in human hepatocellular carcinoma cells, zebrafish and rats. 3086 26