Department of Internal Medicine-Endocrinology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
INTRODUCTION: A missense mutation in the glucagon receptor gene (Gly40Ser) has been associated with type 2 diabetes mellitus in some populations. AIM: To investigate whether this mutation is associated with type 2 diabetes in Brazilian patients and its functional significance in vivo. METHODOLOGY: 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. CONCLUSION: 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.