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Titolo:
PHYSIOLOGICAL AND GENETIC-CHARACTERIZATION OF THE GLY40SER MUTATION IN THE GLUCAGON RECEPTOR GENE IN THE SARDINIAN POPULATION
Autore:
TONOLO G; MELIS MG; CICCARESE M; SECCHI G; ATZENI MM; MAIOLI M; PALA G; MASSIDDA A; MANAI M; PILOSU RM; LI LS; LUTHMAN H; MAIOLI M;
Indirizzi:
UNIV SASSARI,IST CLIN MED,SERV DIABETOL,CATTEDRA MALATTIE METAB,VIALES PIETRO 8 I-07100 SASSARI ITALY KAROLINSKA INST,ROLF LUFT CTR DIABET RES STOCKHOLM SWEDEN OSPED CIVILE,SERV DIABETOL NUORO ITALY DIABETOL OSPED CIVILE LANUSEI ITALY DIABETOL ASL 21 CAGLIARI ITALY
Titolo Testata:
Diabetologia
fascicolo: 1, volume: 40, anno: 1997,
pagine: 89 - 94
SICI:
0012-186X(1997)40:1<89:PAGOTG>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEPENDENT DIABETES-MELLITUS; NIDDM; ASSOCIATION; GLUCOSE;
Keywords:
NIDDM; GENETICS; HYPERTENSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
22
Recensione:
Indirizzi per estratti:
Citazione:
G. Tonolo et al., "PHYSIOLOGICAL AND GENETIC-CHARACTERIZATION OF THE GLY40SER MUTATION IN THE GLUCAGON RECEPTOR GENE IN THE SARDINIAN POPULATION", Diabetologia, 40(1), 1997, pp. 89-94

Abstract

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 notbeen 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 werefound, 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 theGly40Ser 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 because of the reduced stimulation of liver glucose output via the glucagon receptor.

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Documento generato il 05/12/20 alle ore 04:13:43