Association between Polymorphism of the Glycogen Synthase Gene and Non-Insulin-Dependent Diabetes Mellitus

Groop, Leif; Kankuri, Maija; Schalin‐Jäntti, Camilla; Ekstrand, Agneta; Nikula-Ijäs, Pirjo; Widén, Elisabeth; Kuismanen, Esa; Eriksson, Johan G.; Franssila-Kallunki, Anja; Saloranta, Carola; S, Koskimies

doi:10.1056/nejm199301073280102

Cited by 171 publications

(85 citation statements)

References 16 publications

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“…In a previous study in the Finnish population, a rare A2 allele of the Xba I polymorphism in the GSY gene was reported to be associated with NIDDM and a high prevalence of hypertension (14). None of the subjects in this study, however, had A2 allele, indicating that the frequency of A2 allele is very low, if not absent, in the Japanese population and that this marker is not informative in this population.…”

Section: Resultscontrasting

confidence: 70%

“…Glycogen synthase, a key enzyme in this pathway, is therefore a candidate gene for insulin resistance in hypertension. In fact, a rare A2 allele of the XbaI polymorphism in the GSY gene is reported to be associated with NIDDM in which insulin resistance is a characteristic feature and with a high prevalence of hypertension in the Finnish population (14). In the present study in Japanese, however, none of the subjects had this allele.…”

Section: Discussioncontrasting

confidence: 67%

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Analysis of Candidate Genes for Insulin Resistance in Essential Hypertension

et al. 1996

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To clarify the genetic basis of insulin resistance in hypertension, case-control association studies were performed to examine candidate genes for insulin resistance in hypertension. Since the main site of insulin resistance in hypertension is glycogen synthesis in skeletal muscle, genes that encode molecules involved in this pathway, i.e. insulin receptor (INSR), insulin-responsive glucose transporter (GLUT4) and glycogen synthase (GSY), were studied. In addition, since recent studies suggest the contribution of /93 adrenergic receptor to the insulin resistance syndrome, the gene encoding ~3 adrenergic receptor (ADRB3) was also studied. Frequency of homozygotes for common C allele of a microsatellite polymorphism in the INSR gene was higher in the hyperinsulinemia group, but not in the normoinsulinemia group of hypertensive patients than in normotensive control subjects. Insulin sensitivity, however, was not significantly different between hypertensive patients with C/C genotype and those without this genotype. No significant differences were observed in the distribution of alleles or genotypes of the GLUT4, GSY and ADRB3 genes between hyperinsulinemia and normoinsulinemia groups of hypertensive patients or between these groups and the control group. These data suggest that the INSR polymorphism is associated with hyperinsulinemia, but not with insulin resistance, in hypertension. (Hypertens Res 1996; 19 Suppl. I: S31-S34)

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Section: Resultscontrasting

confidence: 70%

Section: Discussioncontrasting

confidence: 67%

Analysis of Candidate Genes for Insulin Resistance in Essential Hypertension

et al. 1996

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“…This relative reduction in glucose oxidation is appreciably higher than that found in studies using indirect calorimetry [15,59,66]. In insulin-dependent (IDDM) patients, the percent glucose oxidized and stored is similar to that in non-diabetic patients, assuming brain glucose oxidation to be i mg 9 kg -1 9 min -1, and heart glucose uptake (0.5 mg-kg -a-min -1, [62]) to consist of glucose oxidation [60].…”

Section: Control Iddm Subjectsmentioning

confidence: 57%

Role of insulin resistance in the pathogenesis of NIDDM

Yki‐Järvinen

1995

Diabetologia

115

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“…We [40,41] and others [42,43] have shown impaired insulinstimulated glucose uptake in first-degree relatives of patients with Type II diabetes. In our own study, insulin secretion measured during a hyperglycaemic clamp was normal when glucose tolerance was normal [15].…”

Section: Discussionmentioning

confidence: 70%

Insulin sensitivity and insulin secretion in monozygotic and dizygotic twins

et al. 2000

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There is plenty of evidence that Type II (non-insulindependent) diabetes mellitusis a disease with a strong genetic predisposition [1±3]. In Finland, the estimated lifetime relative risk (l) of developing diabetes for a sibling to a person with Type II diabetes is about three [4]. This value decreases with age suggesting that environmental factors become more important with increasing age. Obesity and physical inactivity are the most important triggers of the disease. Several twin studies have provided unequivocal support for the genetic nature of the adult-onset type of diabetes, i. Abstract Aims/hypothesis. To estimate the heritability of insulin sensitivity and insulin secretion, both of which are considered to contribute to the development of Type II (non-insulin-dependent) diabetes mellitus. Methods. Intraclass correlation coefficients and heritability estimates for insulin sensitivity (euglycaemic clamp) as well as first-phase and late-phase insulin secretion (intravenous glucose tolerance test) were calculated in 21 monozygotic and 20 dizygotic twin pairs of the same sex between 54 and 72 years of age. Results. Intrapair correlations for all traits were consistently higher in monozygotic than in dizygotic pairs. Insulin secretion correlated significantly only between monozygotic (first-phase r = 0.55; p = 0.003 and late-phase r = 0.66; p < 0.001) twins giving heritability estimates of 0.55 and 0.58, respectively. Insulinstimulated glucose uptake showed a more modest correlation between monozygotic twins (r = 0.46; p = 0.015). The heritability estimate was 0.37. The heritability estimate for waist-to-hip ratio was 0.76 in female and 0.70 in male twins. Conclusion/interpretation. Genetic variability seems to contribute to the variance of insulin sensitivity as well as of insulin secretion. In the current study, genetic variance accounted almost 60 % for the variance in glucose-stimulated insulin secretion and almost 40 % for the variance in insulin-stimulated glucose uptake. Our data is also compatible with findings in monogenic forms of diabetes in which genetic defects in insulin secretion play a predominant part in the pathogenesis of hyperglycaemia. [Diabetologia (2000) Corresponding author: M. Lehtovirta, Helsinki University Central Hospital, Department of Medicine, Division of Internal Medicine, PO Box 346, FIN-00 029 HYKS, Finland Abbreviations: MZ, Monozygotic; DZ, dizygotic; MODY, maturity-onset diabetes of the young; WHR, waist-to-hip ratio; FFM, fat-free mass; SBP, systolic blood pressure; DBP, diastolic blood pressure; FPI, first-phase insulin secretion in IVGTT; LPI, late-phase insulin secretion in IVGTT; Intraclass r, intraclass correlation coefficient; h 2 , heritability; A, additive component of variance; C, variance component due to shared environment; D, variance component due to dominance; E, variance component due to non-shared environmental influences.

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Association between Polymorphism of the Glycogen Synthase Gene and Non-Insulin-Dependent Diabetes Mellitus

Abstract: The Xbal polymorphism of the glycogen synthase gene identifies a subgroup of patients with NIDDM characterized by a strong family history of NIDDM, a high prevalence of hypertension, and marked insulin resistance.

Cited by 171 publications

References 16 publications

Analysis of Candidate Genes for Insulin Resistance in Essential Hypertension

Analysis of Candidate Genes for Insulin Resistance in Essential Hypertension

Role of insulin resistance in the pathogenesis of NIDDM

Insulin sensitivity and insulin secretion in monozygotic and dizygotic twins

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