Abnormally high levels of circulating free fatty acids can lead to pancreatic islet β-cell dysfunction and apoptosis, contributing to β-cell failure in Type 2 diabetes. The NAD+-dependent protein deacetylase Sirtuin-3 (SIRT3) has been implicated in Type 2 diabetes. In this study, we tested whether SIRT3 overexpression affects palmitate-induced β-cell dysfunction in cells of line NIT1, which are derived from mouse pancreatic β-cells. Two different lengths of SIRT3 were overexpressed: full length SIRT3 (SIRT3LF), which was preferentially targeted to mitochondria and partially to the nucleus, and its N-terminal truncated form (SIRT3SF), which was located in the nucleus and cytoplasm. Overexpression of SIRT3LF and SIRT3SF using an adenoviral system alleviated palmitate-induced lipotoxicity such as reduction of cell viability and mitogen-activated protein kinase (MAPK) activation. Chronic exposure to low concentrations of palmitate suppressed glucose-stimulated insulin secretion, but the suppression was effectively reversed by overexpression of SIRT3LF or SIRT3SF. The mRNA levels of the endoplasmic reticulum (ER) stress responsive genes ATF4, GRP94 and FKBP11 were increased by palmitate treatment, but the increases were completely inhibited by SIRT3LF overexpression and less effectively inhibited by SIRT3SF overexpression. This result suggests that overexpression of SIRT3 inhibits induction of ER stress by palmitate. Collectively, we conclude that overexpression of SIRT3 alleviates palmitate-induced β-cell dysfunction.

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In this study, a 40% ethanol extract of Chinese yam flour (Dioscoreae rhizoma), containing 177 +/- 58 microg/mL of dioscin, was tested in order to evaluate its pharmacological effects on the gastrointestinal tracts of Sprague-Dawley rats. Via the ingestion of the Chinese yam extract, the secretion of gastric acid was suppressed in the rats, and gastrointestinal motility increased by as much as 10%. The fecal quantity of rats fed on the Chinese yam extract also increased, by more than 40% as compared with that of the controls. The Chinese yam extract was found not to affect the growth of normal intestinal bacteria. However, a great deal of lactose-fermenting bacteria was observed in the fecal samples of rats fed for 6 weeks on 2% Chinese yam extract. This finding would appear to suggest that Chinese yam extract not only induces an improvement in digestive capability, but also affects the conversion of some intestinal flora to helpful bacteria. Our serochemical analyses indicated that serum glucose, neutral lipid, and total cholesterol levels were reduced to some degree by long-term feeding on Chinese yam extract. This finding bolsters the notion that Chinese yam extract may prove helpful as a digestion-aiding agent for patients suffering from hyperglycemia or hyperlipidemia.

Activation of the Wnt/β‐catenin signaling pathway inhibits adipogenesis, while disruption of Wnt signaling leads to spontaneous adipogenesis. CCAAT/enhancer binding protein β (C/EBPβ) is rapidly induced in early stages of adipogenesis and is responsible for transcriptional induction of two major adipogenic transcription factors, peroxisome proliferator‐activated receptor γ (PPARγ) and C/EBPα. In this study, we examined whether C/EBPβ is involved in the suppression of Wnt/β‐catenin signaling during adipogenesis. Knockdown of C/EBPβ expression not only inhibited adipogenesis but also maintained active Wnt/β‐catenin signaling, after addition of adipogenic inducers. In contrast, overexpression of C/EBPβ substantially inhibited Wnt signaling. Interestingly, our data showed that C/EBPβ is involved in the expression of Wnt10b, a major Wnt ligand in preadipocytes, even though C/EBPβ is not an essential factor to regulate Wnt10b expression during adipogenesis, and that C/EBPβ inhibits Wnt10b promoter activity by directly binding to specific regions of the promoter. These results suggest a dual function of C/EBPβ: stimulating expression of adipogenic genes and inhibiting Wnt signaling.