A case of Cowden disease shows enhanced insulin sensitivity

A 51-year-old man diagnosed with Cowden disease based on multiple facial trichilemmoma, oral mucosal papillomatosis, palmo-planter keratosis and muliple hamartomatous polyps in the gastrointestinal tract had had a heterozygous flameshift mutation identified in his PTEN gene (4 base insertion after codon 221), believed to be responsible for the disease. We examined his insulin sensitivity. His fasting blood glucose was 92 mg/dl while his fasting immunoreactive insulin (IR) was 1.3 μU/ml (HOMA-R 0.30) and C peptide immunoreactivity below 0.1 ng/ml. An euglycemic hyperinsulinemic clamp study showed that mean glucose infusion, which mainly reflects insulin sensitivity in the skeletal muscle, rose to 14.1 mg/kg/min (normal: almost 8.0-10.0 mg/kg/min) when serum IR was 70.3 μ U/ml at a constant insulin infusion of 1.5 mU/kg/ min. The portal glucose uptake to the liver was 79.9, which also increased compared to normal subjects (approximately 30-40%). PTEN is a lipid phosphatase against phosphatidylinositol 3,4,5-triphosphate and may negatively regulate insulin singaling in vitro and in vivo. This case suggests that PTEN protein may play an important role on insulin sensitivity and glucose homeostasis in the human being.