For centuries, Berberine has been used in the treatment of enteritis in China, and it is also known to have anti-hyperglycemic effects in type 2 diabetic patients. However, as Berberine is insoluble and rarely absorbed in gastrointestinal tract, the mechanism by which it works is unclear. We hypothesized that it may act locally by ameliorating intestinal barrier abnormalities and endotoxemia. A high-fat diet combined with low-dose streptozotocin was used to induce type 2 diabetes in male Sprague Dawley rats. Berberine (100 mg/kg) was administered by lavage to diabetic rats for 2 weeks and saline was given to controls. Hyperinsulinemia and insulin resistance improved in the Berberine group, although there was no significant decrease in blood glucose. Berberine treatment also led to a notable restoration of intestinal villi/mucosa structure and less infiltration of inflammatory cells, along with a decrease in plasma lipopolysaccharide (LPS) level. Tight junction protein zonula occludens 1 (ZO1) was also decreased in diabetic rats but was restored by Berberine treatment. Glutamine-induced glucagon-like peptide 2 (GLP2) secretion from ileal tissue decreased dramatically in the diabetic group but was restored by Berberine treatment. Fasting insulin, insulin resistance index, plasma LPS level, and ZO1 expression were significantly correlated with GLP2 level. In type 2 diabetic rats, Berberine treatment not only augments GLP2 secretion and improves diabetes but is also effective in repairing the damaged intestinal mucosa, restoring intestinal permeability, and improving endotoxemia. Whether these effects are mechanistically related will require further studies, but they certainly support the hypothesis that Berberine acts via modulation of intestinal function.
C Y Shan, J H Yang, Y Kong, X Y Wang, M Y Zheng, Y G Xu, Y Wang, H Z Ren, B C Chang, and L M Chen
F S Khan-Dawood, J Yang, K Anwer, and M Y Dawood
Oxytocin has been identified in both non-human primate and human corpora lutea of the menstrual cycle by RIA, immunocytochemistry and HPLC. Evidence for the transcription of the oxytocin gene in this tissue using PCR is available. Oxytocin receptors have been characterized by biochemical procedures. However, there is some debate as to whether the oxytocin identified in these tissues is biologically active and has a role in luteal function. In this study we have demonstrated that oxytocin isolated by gel chromatography of tissue extracts from the baboon and the human corpus luteum is biologically active as determined in a rat uterine bioassay. Since both oxytocin and its receptors are present in these tissues, it is suggested that oxytocin in the human and non-human primate corpora lutea has a functional role.
Journal of Endocrinology (1995) 147, 525–532
Y Yang, J Cao, W Xiong, J Zhang, Q Zhou, H Wei, C Liang, J Deng, T Li, S Yang, and L Xu
It has been documented that stress or glucocorticoids have conflicting effects on memory under different conditions. However, it is not fully understood why stress can either impair or enhance memory. Here, we have examined the performance of six age groups of Wistar rats in a water maze spatial task to evaluate the effects of stress under different conditions. We found that the impairment or enhancement effect of an 'elevated platform' (EP) stress on memory was dependent on previous stress experience and on age. EP stress impaired memory retrieval in water maze naive animals, but enhanced rather than impaired memory retrieval in young water maze stress-experienced animals. Furthermore, exogenously applied corticosterone or foot shock stress before water maze training prevented the impairment of memory retrieval that should be induced by treatment with corticosterone or foot shock before the 'probe trial'. Again, memory retrieval was enhanced in young animals under these conditions, and this enhancement can be prevented by the glucocorticoid receptor antagonist RU 38486. Thus, glucocorticoid receptor activation not only induced impairment of memory but also increased the capacity of young animals to overcome a later stress. The present findings suggest that the effect of stress on memory can be switched from impairment to enhancement dependent on both stress experience and age.
L Yang, CB Kuo, Y Liu, D Coss, X Xu, C Chen, ML Oster-Granite, and AM Walker
During rat pregnancy initial high concentrations of prolactin (PRL) decline by about day 9, concomitant with an increase in the ratio of unmodified to phosphorylated PRL. The physiological significance of both the decline in total PRL and the change in ratio of the two PRLs is unknown. To test the importance of each, either unmodified PRL (U-PRL) or a molecular mimic of phosphorylated PRL (PP-PRL) were continuously administered to rats throughout pregnancy. A dose of 6 microg/24 h resulted in circulating concentrations of 50 ng/ml of each administered PRL and had little effect on the pregnancy itself. After birth, pups were killed and various tissues examined. In the pup lungs, exposure to additional PP-PRL caused a reduction in epithelial integrity and an increase in apoptosis, whereas exposure to additional U-PRL had beneficial, anti-apoptotic effects. In the heart, PP-PRL caused an apparent developmental delay, whereas U-PRL promoted tissue compaction. In the blood, U-PRL increased the number of mature red blood cells at the expense of white blood cell production. Within the white blood cell population, myelopoiesis was favored at the expense of lymphopoiesis. PP-PRL, in contrast, had a less dramatic influence on the hematopoietic compartment by promoting red blood cell maturation and granulocyte production. In the thymus, exposure to PP-PRL caused accumulation of apoptotic thymocytes in enlarged glands, whereas exposure to U-PRL resulted in smaller thymi. In the spleen, exposure to U-PRL increased cellularity, with the majority of cells belonging to the erythroid series - a finding consistent with increased red blood cells in the circulation. Exposure to PP-PRL was without discernible effect. In all of these tissues, the contrasting effects of the two PRLs indicate that the absolute concentration of PRL is not crucial, but that the ratio of U-PRL to PP-PRL has a profound effect on tissue development. In brown fat, both PRL preparations decreased the number of lipid droplets. This result is therefore probably a consequence of the increase in total PRL. The results of this study attest to the importance of the U-PRL:PP-PRL ratio normally present during pregnancy and have provided clues as to the possible pathogenesis of a variety of neonatal problems.
W Yin, D Liao, M Kusunoki, S Xi, K Tsutsumi, Z Wang, X Lian, T Koike, J Fan, Y Yang, and C Tang
The synthetic compound NO-1886 (ibrolipim) is a lipoprotein lipase activator that has been proven to be highly effective in lowering plasma triglycerides. Recently, we found that NO-1886 also reduced plasma free fatty acids and glucose in high-fat/high-sucrose diet-induced diabetic rabbits. In the current study, we investigated the effects of NO-1886 treatment on ectopic lipid deposition and the islet pathology in miniature swine fed a high-fat/high-sucrose diet. Our results showed that feeding this diet to miniature swine caused insulin resistance, increased lipid deposition in non-adipose tissue, such as in the heart, skeletal muscle, liver and pancreas, and also caused pancreatic beta cell damage. However, supplementing 1% NO-1886 (200 mg/kg per day) into the high-fat/high-sucrose diet decreased ectopic lipid deposition, improved insulin resistance, and alleviated the beta cell damage. These results suggest that improvement of lipid disorder, non-adipose tissue steatosis and insulin resistance may be very important for the protection of beta cell damage. Therefore, NO-1886 is potentially beneficial for the treatment of insulin-resistance syndrome.
A. M. BOOL, G. H. GRAY II, M. E. HADLEY, C. B. HEWARD, V. J. HRUBY, T. K. SAWYER, and Y. C. S. YANG
Heat–alkali treatment of synthetic α- and β-melanocyte-stimulating hormones (MSH), known to cause racemization of amino acids within the peptides, results in prolongation of the darkening (melanophore dispersion) effect of these hormones on frog and lizard skins in vitro. Skins remain darkened for hours or even days if supramaximal concentrations of the racemized hormones are used. This response can be partially reversed by melatonin or noradrenaline. Heat–alkali treatment of α-MSH at either 60 or 97 °C results in a retardation of the response of the skins to the racemized peptides. In contrast, the response of frog skins to heat–alkali-treated β-MSH is immediately enhanced and potentiated. Heat–alkali treatment also prolongs and potentiates the activity of synthetic [des-acetyl]-α-MSH (in contrast to the retardation effect on the natural acetylated peptide). These data suggest a role for the N-acetyl group in the retardation phenomenon. The activity of synthetic [2-d-tyrosine]-α-MSH is much lower than that of α-MSH itself, indicating that heat–alkali treatment of the hormone may produce either potentiation or partial inactivation of the peptide, depending on the site of racemization.