Effects of medicinal plant extracts on gluconeogenesis

Correspondence: Adolfo Andrade-Cetto Laboratorio de Etnofarmacologia, Departamento de Biologia Celular, Facultad de Ciencias, Universidad Nacional Autonoma de Mexico, Coyoacan 04510, D.F. Mexico Email aac@ciencias.unam.mx Abstract: On a global level, type 2 diabetes mellitus (T2DM) is the most common endocrine disorder. T2DM is defined as an elevated blood glucose level associated with the absence of or inadequacy in pancreatic insulin secretion. The liver plays a key role in maintaining blood glucose levels during fasting by synthesizing glucose, mainly from lactate and amino acids through a process called gluconeogenesis. Because hepatic glucose production is increased at least twofold in patients with T2DM, targeting this pathway may lead to a blood glucose reduction in these patients. Botanical agents show promise for the development of new compounds to treat T2DM. Important mechanisms of action function via the inhibition of gluconeogenesis can occur in one of five ways: direct enzyme inhibition; through the downregulation of mRNA levels of fructose-1,6-bisphosphatase and glucose-6-phosphatase (G-6-P); through the activation of AMP-activated protein kinase, which leads to decreased levels of cAMP response elementbinding protein, a key transcription factor for gluconeogenic enzyme phosphorylation; through the expression of the glucokinase gene, which stimulates glucokinase activity and inhibits G-6-P; and through the inhibition of phosphoenolpyruvate carboxykinase, which decreases gluconeogenesis and enzymatically inhibits G-6-P and fructose-1,6-diphosphatase.