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 dephosphorylate phosphatidylinositol 3, 4, 5-triphosphate, a key molecule involved in the insulin signaling pathway. The PTEN may act, therefore, as a negative regulator of insulin signaling. The patient with Cowden disease, having a heterozygous PTEN/MMAC1 gene mutation, a C to T substitution of a single base at codon 130, was suspected to have decreased amount of PTEN protein with 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 rapid clearance of blood glucose than was observed in 5 control subjects, indicating the presence of insulin hypersensitivity in the patient. The euglycemic hyperinsulinemic clamp study provided additional evidence.
Minami Wakayama National Hospital Takinaicho 27-1, Wakayama, Japan.
S
S
Iida
A
A
Ono
K
K
Sayama
T
T
Hamaguchi
H
H
Fujii
H
H
Nakajima
M
M
Namba
T
T
Hanafusa
Y
Y
Matsuzawa
K
K
Moriwaki
D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D003062:Codon / Q000235:genetics; D016147:Genes, Tumor Suppressor; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006223:Hamartoma Syndrome, Multiple / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007328:Insulin; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D051059:PTEN Phosphohydrolase; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics*; D017354:Point Mutation; D013728:Terminator Regions, Genetic; D025521:Tumor Suppressor Proteins
D001786:Blood Glucose; D003062:Codon; D007328:Insulin; D018129:Phosphatidylinositol Phosphates; D025521:Tumor Suppressor Proteins; C060974:phosphatidylinositol 3,4,5-triphosphate; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D005947:Glucose