METHODS AND RESULTS: Effects of GBR, brown rice, and white rice (WR) on fasting plasma glucose and selected genes were studied in type 2 diabetic rats. GBR reduced plasma glucose and weight more than metformin, while WR worsened glycemia over 4 weeks of intervention. Through nutrigenomic suppression, GBR downregulated gluconeogenic genes (Fbp1 and Pck1) in a manner similar to, but more potently than, metformin, while WR upregulated the same genes. Bioactives (gamma-amino butyric acid, acylated steryl glycoside, oryzanol, and phenolics) were involved in GBR's downregulation of both genes. Plasma glucose, Fbp1 and Pck1 changes significantly affected the weight of rats (p = 0.0001).
CONCLUSION: The fact that GBR downregulates gluconeogenic genes similar to metformin, but produces better glycemic control in type 2 diabetic rats, suggests other mechanisms are involved in GBR's antihyperglycemic properties. GBR as a staple could potentially provide enhanced glycemic control in type 2 diabetes mellitus better than metformin.
RESULTS: The effect of cAMP and glucocorticoid treatment on Creb3l1 was investigated in both AtT20 cells and hypothalamic organotypic cultures. The expression of Creb3l1 was increased in both mRNA and protein level by treatment with forskolin, which raises intracellular cAMP levels. Activation of cAMP by forskolin also increased Avp promoter activity in AtT20 cells and this effect was blunted by shRNA mediated silencing of Creb3l1. The forskolin induced increase in Creb3l1 expression was diminished by combined treatment with dexamethasone, and, in vivo, intraperitoneal dexamethasone injection blunted the increase in Creb3l1 and Avp expression induced by hyperosmotic stress.
CONCLUSION: Here we shows that cAMP and glucocorticoid positively and negatively regulate Creb3l1 expression in the rat hypothalamus, respectively, and regulation of cAMP on AVP expression is mediated through CREB3L1. This data provides the connection between CREB3L1, a newly identified transcription factor of AVP expression, with the previously proposed mechanism of Avp transcription which extends our understanding in transcription regulation of Avp in the hypothalamus.