Role of the Gly40Ser mutation in the glucagon receptor gene in Brazilian patients with type 2 diabetes mellitus.
BACKGROUND
A missense mutation in the glucagon receptor gene (Gly40Ser) has been associated with type 2 diabetes mellitus in some populations.


OBJECTIVE
To investigate whether this mutation is associated with type 2 diabetes in Brazilian patients and its functional significance in vivo.


METHODS
One hundred fifteen patients with type 2 diabetes and 115 control subjects were screened by restriction-enzyme digestion with BstE II. The in vivo implications were investigated by 1 mg glucagon intravenous injection and plasma C-peptide (before and after 6 minutes) and glucose measurements (before and after 30, 60, 90, and 120 minutes), and first-phase insulin response (1 + 3 minutes) to intravenous glucose tolerance test. These procedures were performed in two groups of patients with diabetes, which differed only by the presence or absence of the Gly40Ser mutation, and two groups of control subjects.


RESULTS
The mutation was detected in two patients with diabetes (1.7%) and in four control subjects (3.5%) (not significant). Patients with diabetes and carriers of Gly40Ser showed basal C-peptide levels significantly lower than noncarriers (0.70 ng/mL versus 1.50 ng/mL, p = 0.008). No differences were found between Gly40Ser carriers and noncarriers in control subjects within the parameters studied.


CONCLUSIONS
Our results show that the Gly40Ser mutation in the glucagon receptor gene is not associated with type 2 diabetes in a Brazilian population. However, a reduction of insulin secretion was observed in Gly40Ser carriers.
Shiota
Debora
D
Department of Internal Medicine-Endocrinology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
Kasamatsu
Teresa
T
Dib
Sergio A
SA
Chacra
Antonio R
AR
Moisés
Regina S
RS
D000328:Adult; D000368:Aged; D001938:Brazil; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005765:Gastrointestinal Agents / Q000097:blood; D005820:Genetic Testing; D005934:Glucagon / Q000097:blood; D005951:Glucose Tolerance Test; D006579:Heterozygote; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D018027:Receptors, Glucagon / Q000235:genetics*
D005765:Gastrointestinal Agents; D007328:Insulin; D018027:Receptors, Glucagon; D005934:Glucagon