Accelerated decline of blood glucose after intravenous glucose injection in a patient with Cowden disease having a heterozygous germline mutation of the PTEN/MMAC1 gene

The PTEN/MMAC1, a putative tumor suppressor, has been demonstrated to depho sphorylate phosphatidylinositol 3, 4, 5-triphosphate, a key molecule involv ed in the insulin signaling pathway. The PTEN may act, therefore, as a nega tive regulator of insulin signaling The patient with Cowden disease having a heterozygous PTEN/MMAC1 gene mutation a C to T substitution of a single b ase at codon 130, wets suspected to have decreased amount of PTEN protein w ith phosphatase signature motif. We thought that the patient might be more sensitive to insulin than normal subjects. As expected, administration of a bolus of glucose resulted in a more vapid clearance of blood glucose than was observed in 5 control subjects, indicating the presence of insulin hype rsensitivity in the patient. The euglycemic hyperinsulinemic clamp study pr ovided additional evidence.