2,4-thiazolidinedione (T-174) has been investigated for the treatment of Type 2 Diabetes mellitus in Japan. Oral administration of T-174 markedly improved hyperglycaemia, hyperinsulinaemia, hyperlipidaemia, and glucose intolerance in genetically obes...
e and diabetic yellow KK (KK-Ay) mice. A hyperinsulinaemic euglycaemic clamp study in Zucker fatty rats showed an amelioration of whole-body insulin resistance by the T-174 treatment. Insulin-stimulated glucose metabolism was enhanced in adipocytes from KK-Ay mice treated with T-174. The insulin receptor number of the adipocytes was increased without a change in the affinity of the receptor. The hypomagnesaemia in KK-Ay mice was completely restored by T-174. T-174, developed as an antidiabetic drug, stimulated the transcription of PPAR gamma and the adipocyte differentiation of 3T3-L1 cells. T-174 induced the interaction between PPAR gamma and CBP (cAMP response element binding protein (CREB) binding protein), a co-factor of various transcription regulators.
