Decrease of plasma glucose by allantoin, an active principle of yam ( Dioscorea spp.), in streptozotocin-induced diabetic rats.

The effect of allantoin, an active component of yam, on plasma glucose of streptozotocin-induced diabetic rats (STZ-diabetic rats) is investigated. Allantoin decreased plasma glucose levels in a dose-related manner, which was reduced by pretreatment with naloxone or naloxonazine. A concomitant increase in plasma ß-endorphin, detected by enzyme-linked immunosorbent assay, was observed. Moreover, allantoin enhanced ß-endorphin release from the isolated adrenal medulla of STZ-diabetic rat in a dose-related manner. However, its plasma glucose lowering action was reduced but not totally abolished by bilateral adrenalectomy. Furthermore, allantoin directly increased radioactive glucose uptake in isolated skeletal muscle, and repeated administration for 3 days increased GLUT4 mRNA and protein levels in muscle. This effect was markedly reduced in STZ-diabetic rats with bilateral adrenalectomy. This study suggests that allantoin increases GLUT4 gene expression in muscle by increasing ß-endorphin secretion from the adrenal gland in STZ-diabetic rats.

Insulin resistance without obesity induced by cotton pellet granuloma in mice.

Obesity leads to insulin resistance because the larger adipocytes in obese persons secrete proinflammatory cytokines that cause chronic inflammation in adipose tissue. This, in turn, leads to the alteration of adipokine secretion, which can induce insulin resistance. However, the development of insulin resistance without obesity is still obscure. We aimed to use an animal inflammation model with cotton pellet granuloma (CPG) in adipose tissue to characterize insulin resistance formation. We found that CPG in epididymal white adipose tissue (WAT), rather than in interscapular brown adipose tissue, impaired insulin sensitivity, and glucose utilization, and that it decreased levels of phosphoinsulin receptor and phospho-Akt in both muscle and liver tissue, but that it did not modify the body weight or food intake in mice. Macrophage infiltration in adipose tissue, leukocyte counts, monocyte chemoattractant protein-1, and interleukin-6 were elevated in CPG-treated mice. However, we found a marked decrease of plasma adiponectin only in the WAT group, which might have been because of the lower level of peroxisome proliferator-activated receptor-gamma in WAT. These results show that granuloma formation in WAT by implantation of a cotton pellet may induce insulin resistance under nonobese condition through circulating inflammatory mediators, especially the low level of adiponectin.

Role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the action of ginsenoside Rh2 against beta-amyloid-induced inhibition of rat brain astrocytes.

Ginsenoside, the active principles in Panax ginseng root, has been demonstrated to show neurotrophic and neuroprotective actions for prevention of neuron degeneration. Deposition of beta-amyloid peptide (Abeta) causes neurotoxicity through the formation of plaques in brains with Alzheimer's disease. Pituitary adenylate cyclase-activating polypeptide (PACAP) is introduced as a neurotrophic factor to promote cell survival. However, effect of Rh2, one of ginsenosides, on PACAP expression induced by Abeta remains unclear. In the present study, we found that Rh2 stimulates PACAP gene expression and cell proliferation in type I rat brain astrocytes (RBA1) cells and both effects were not modified by the estrogen antagonists (MPP or ICI 182780). Also, Rh2 ameliorates the RBA1 growth inhibition of Abeta. Moreover, blockade of PACAP receptor PAC1 using PACAP (6-38) inhibits all the actions of Rh2. These results suggest that Rh2 can induce an increase of PACAP to activate PAC1, but not estrogen receptor, and thereby leads to attenuate Abeta-induced toxicity. Thus, ginseng seems useful in the prevention of dementia.