Glucagon receptor gene mutation in NIDDM

Jaksch, Michaela; Hofmann, Susanna M.; Kd, Gerbitz

doi:10.1007/bf00403973

Cited by 3 publications

(3 citation statements)

References 2 publications

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“…Genetically, Sardinians are very different from most European populations since the colonization dates back to pre-Neolithic times, and cultural, linguistic and geographical factors have promoted isolation of the Sardinians [11,12]. The Gly40Ser amino acid substitution has been observed at different prevalences in different populations [3][4][5][6], and also within the same population [7,8]. These data fit well with our findings in the different regions of Sardinia.…”

Section: Discussionsupporting

confidence: 80%

Physiological and genetic characterization of the Gly40Ser mutation in the glucagon receptor gene in the Sardinian population

et al. 1997

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Non-insulin-dependent diabetes mellitus (NIDDM) is a multifactorial disorder, displaying heterogeneity both at the genotype and phenotype levels. It affects 3-8 % of the Caucasian population over 45 years [1,2]. The genetic susceptibility to NIDDM is likely to involve separate but interrelated functions (for example insulin secretion, insulin resistance, obesity, abdominal fat patterning, intermediary metabolism, etc.) which have clinical consequences as a result of environmental influence. The increased understanding of the physiology and molecular biology of NIDDM has led to the identification of a number of genes. Among different candidate genes investigated so far, a possible association between NIDDM and a Diabetologia (1997) 40: 89-94 Physiological and genetic characterization of the Gly40Ser mutation in the glucagon receptor gene in the Sardinian population Summary A Gly40Ser amino acid substitution in the glucagon receptor gene has been associated with non-insulin-dependent diabetes mellitus (NIDDM), but the questions raised about its physiological implications have not been resolved. The aim of this study was to determine the frequency of the Gly40Ser mutation in different regions of Sardinia and to investigate the physiological implications of the mutation in glucose and insulin homeostasis. We studied a population of 691 subjects, selected on the basis of their Sardinian origin. Only heterozygous subjects were found, 21 of 574 (3.6 %) in NIDDM patients and 5 of 117 in non-diabetic subjects (4.2 %). In northern Sardinia 3.4 % of the NIDDM patients were carriers of the Gly40Ser substitution, 1.4 % in central Sardinia, while 7.6 % carried the substitution in the Southern part. No significant differences were found between hypertensive and normotensive subjects with respect to the presence of Gly40Ser. Ten subjects with Gly40Ser were carefully matched for diabetic state, BMI, age, sex, and geographical origin with 10 patients with Gly40, and a glucagon infusion test was performed using 1, 3, 9 and 27 ng glucagon kg -1 ⋅ min -1 for 30 min. Blood for determination of glucose, glucagon, and insulin concentrations was drawn at 15-min intervals from the Controlateral arm. Plasma glucagon increased dose-dependently during the infusion with no significant difference between the two groups. Carriers of Gly40Ser had a significantly lower (p < 0.02) increase in plasma glucose concentration in response to glucagon infusion compared to Gly40 homozygous subjects at all times, while the plasma insulin increase was not significantly different at any time. In conclusion, our results indicate that the Gly40Ser variation is not associated with NIDDM in the Sardinian population, and that its frequency varies in different parts of Sardinia. Moreover in vivo Gly40Ser plays a physiological role in the glucose homeostasis under glucagon control both in NIDDM and non-diabetic subjects. This latter result suggests that this amino acid substitution in the glucagon receptor may lead to a decreased blood glucose concentration bec...

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Section: Discussionsupporting

confidence: 80%

Physiological and genetic characterization of the Gly40Ser mutation in the glucagon receptor gene in the Sardinian population

et al. 1997

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“…Contrary to the results concerning the French, Sardinian (Hager et al, 1995) and the British (Gough et al, 1995) populations and in accordance with those in Japan (Fujisawa et al, 1995), Finnland (Huang et al, 1995), The Netherlands ('t Hart et al, 1995) and Germany (Ristow et al, 1996;Jaksch et al, 1996) none of the NIDDM patients in our study had the mutation in the GCG-R gene (Gly4OSer) and a founder effect was not observed in the Russian patients.…”

Section: Discussionsupporting

confidence: 52%

“…This mutation was also found in about 2% of diabetic patients from different areas of the United Kingdom (Gough et al, 1995). However, in Japan (Fujisawa et al, 1995), Finnland (Huang et al, 1995), The Netherlands ('t Hart et al, 1995 and Germany (Ristow et al, 1996;Jaksch et al, 1996) no such mutations were detected.…”

Section: Introductionmentioning

confidence: 91%

Polymorphism of the glucagon receptor gene and non-insulin-dependent diabetes mellitus in the Russian population

Babadjanova

Reincke²,

Mora³

et al. 2009

Exp Clin Endocrinol Diabetes

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Recently, a missense mutation in the glucagon receptor (GCG-R) gene causing a Gly to Ser change at codon 40 (Gly40Ser) has been associated and linked with non-insulin-dependent diabetes mellitus (NIDDM). We screened 150 unrelated NIDDM patients and 109 non-diabetic subjects for the presence of the Gly40Ser polymorphism by use of polymerase chain reaction-restriction fragment length polymorphism in the Russian population. None of the NIDDM patients showed this polymorphism. In contrast, two of the control subjects were heterozygous carriers of the polymorphism. Both were healthy females without a family history of diabetes. The body mass index, age, and 2-h blood glucose levels of the two subjects with the polymorphism were similar to those of the control subjects homozygous for the wild-type. Our results suggest that Gly40Ser polymorphism of the GCG-R gene is not associated with NIDDM in the Russian population and point to the genetic heterogeneity of NIDDM in different ethnic groups.

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Analysis of the Gly40Ser Polymorphism in the Glucagon Receptor Gene in a German Non-Insulin-Dependent Diabetes Mellitus Population

Ambrosch¹,

Lobmann²,

Dierkes³

et al. 1999

CCLM

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A heterozygous polymorphism changing GGT40 (Gly) to AGT40 (Ser) in the glucagon receptor gene (GCG-R) was reported to be associated with non-insulin-dependent diabetes mellitus (NIDDM). A possible involvement of this polymorphism in impaired glucose tolerance was also suggested in a French population. However, the prevalence of this polymorphism differs markedly among different ethnic groups, whereby the results in German populations were found to be contradictory. We thus investigated the association of this mutation with NIDDM and healthy subjects in 508 German subjects (196 NIDDM, and 312 controls). None of the control subjects, but one of the NIDDM patients demonstrated the Gly40Ser polymorphism. Since no first-degree relative of the index patient had this genetic variance, a de novo mutation is suggested. Although the frequency of the Gly40Ser polymorphism in NIDDM observed in France is not confirmed in our population, this genetic variance is also evident in Germany.

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Glucagon receptor gene mutation in NIDDM

Cited by 3 publications

References 2 publications

Physiological and genetic characterization of the Gly40Ser mutation in the glucagon receptor gene in the Sardinian population

Physiological and genetic characterization of the Gly40Ser mutation in the glucagon receptor gene in the Sardinian population

Polymorphism of the glucagon receptor gene and non-insulin-dependent diabetes mellitus in the Russian population

Analysis of the Gly40Ser Polymorphism in the Glucagon Receptor Gene in a German Non-Insulin-Dependent Diabetes Mellitus Population

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