Synthetic Antidiabetic Drugs Research Articles

Analysis of synthetic anti-diabetic drugs in adulterated traditional Chinese medicines by high-performance capillary electrophoresis

Four synthetic anti-diabetic drugs, acetohexamide (ACE), chlorpropamide (CHL), glibenclamide (GLI) and tolbutamide (TOL), which can be found as adulterants in traditional Chinese medicines (TCMs) were assayed simultaneously using high-performance capillary electrophoresis (HPCE) in 4 min with UV detection at 200 nm. The electrolyte was a buffer solution containing 100 mM phosphate buffer (NaH 2PO 4/Na 2B 4O 7, pH 7.5). Applied voltage was 15.0 kV and temperature was 30 °C. 2-(4-Hydroxyphenyl) ethyl ammonium chloride (HEA) was used as an internal standard. The effects of buffer concentration, pH and supplied voltage on separation were investigated. The relative standard deviations (R.S.D.) of these anti-diabetic drugs for intra-day and inter-day analyses were 0.23–4.27 and 1.23–6.33%, respectively. The recoveries of the synthetic drug adulterants in traditional Chinese medicinal formula ranged from 81.3 to 105.5%. GLI was found and determined in a real sample of TCM.

Inhibition of Adipogenesis by a COOH-Terminally Truncated Mutant of PPARγ2 in 3T3-L1 Cells

Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that is thought to be an important regulator of adipocyte differentiation. This ligand-dependent transcription factor is also activated by thiazolidinediones, a new class of synthetic antidiabetic drugs, resulting in a marked adipogenic response in cultured cells and enhanced insulin sensitivity in vivo. The importance of the COOH-terminal region of PPARγ2 in thiazolidinedione-induced adipogenesis has now been investigated by expression of a mutant protein (PPARγ2-ΔC) that lacks the COOH-terminal 16 amino acids of full-length PPARγ2. The mutant protein failed to bind a thiazolidinedione ligand, but its ability to bind the peroxisome proliferator response element was similar to that of the wild-type protein. Expression of PPARγ2-ΔC inhibited the thiazolidinedione-induced increase in trans-activation activity of endogenous PPARγ in CV-1 cells. Furthermore, the mutant protein prevented thiazolidinedione-induced adipogenesis in 3T3-L1 cells, whereas expression of recombinant wild-type PPARγ2 promoted adipogenesis. These data show not only that the COOH-terminal region of PPARγ2 is indispensable for thiazolidinedione-induced adipogenesis mediated by this protein in 3T3-L1 cells, but also that the PPARγ2-ΔC mutant acts in a dominant negative manner by interfering with the access of endogenous PPARγ to the peroxisome proliferator response element of target genes.