Thesis (Ph.D.)--Chulalongkorn University, 2005

p-MCA decreased fasting plasma glucose and increased insulin concentrations in both normal and diabetic rats. In addition, it improved also glucose intolerance in diabetic rats. During 4 weeks of the study. P-MCA reduced plasma glucose concentration in diabetic rats but not in normal rats. p-MCA reduced the excessive activities of hepatic glucose-6-phosphatase, and increased hepatic hexokinase, glucokinase, phosphofructokinase, hepatic glycogen in diabetic rats. p-MCA increased insulin secretion from the perfused rat pancreas and INS-1 cells in a concentration-dependent manner. In addition, p-MCA increased intracellular Ca[superscript2]+ concentration ([Ca[superscript2]+]) in INS-1 cells. The p-MCA-induced insulin secretion and rise in [Ca[superscript2]+] were markedly inhibited in the absence of extracellular Ca[superscript2]+ or in the presence of an L-type Ca[superscript2]+ channel blocker nimodipine. Diazoxide, and ATP-sensitive K+ channel opener, did not alter p-MCA-induced insulin secretion, nor [Ca[superscript2]+] response. These results suggested that p-MCA increased Ca[superscript2]+ influx via the L-type Ca[superscript2]+ channels, but not through the closure of ATP-sensitive K+ channels In addition, p-MCA enhanced glucose- and glyburide-induced insulin secretion and it also the increase in insulin secretion and a rise of [Ca[superscript2]+] induced by KCI-and Bay K 8644, an L-type Ca2+ channel. Furthermore, p-MCA increased cyclic AMP content of INS-1 cells and enhanced the increase of cyclic AMP content induced by forskolin ; however p-MCA failed to enhance the effect of a phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. P-MCA was a potent competitive inhibitor against yeast alpha-glucosidase However, it had no inhibitory activities on mammalian alpha-glucosidases and alpha-amylase.