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Monoallelic expression of several genes has been observed in mice in which transcripts from parental homologues are distinguishable, but this phenomenon has not been demonstrated in humans. One monoallelically expressed murine gene, H19, encodes an abundant fetal RNA. We have found restriction site polymorphisms in the human H19 gene, located on chromosome 11p15, and examined the representation of these polymorphisms in cDNAs from fetal organs. Expression of H19 is largely or exclusively from a single allele; a similar analysis of the WT1 gene, on 11p13, shows biallelic expression. In the context of previous studies of 11p15 allelic losses in human embryonal tumours, our findings support the possibility of single-step inactivation of monoallelically expressed growth-regulating genes in human oncogenesis.

Background and Purpose Recent reports have suggested that salidroside could protect cardiomyocytes from oxidative injury and stimulate glucose uptake in skeletal muscle cells by activating AMP‐activated protein kinase (AMPK). The aim of this study was to evaluate the therapeutic effects of salidroside on diabetic mice and to explore the underlying mechanisms. Experimental Approach The therapeutic effects of salidroside on type 2 diabetes were investigated. Increasing doses of salidroside (25, 50 and 100 mg·kg−1·day−1) were administered p.o. to db/db mice for 8 weeks. Biochemical analysis and histopathological examinations were conducted to evaluate the therapeutic effects of salidroside. Primary cultured mouse hepatocytes were used to further explore the underlying mechanisms in vitro. Key Results Salidroside dramatically reduced blood glucose and serum insulin levels and alleviated insulin resistance. Hypolipidaemic effects and amelioration of liver steatosis were observed after salidroside administration. In vitro, salidroside dose‐dependently induced an increase in the phosphorylations of AMPK and PI3K/Akt, as well as glycogen synthase kinase 3β (GSK3β) in hepatocytes. Furthermore, salidroside‐stimulated AMPK activation was found to suppress the expression of PEPCK and glucose‐6‐phosphatase. Salidroside‐induced AMPK activation also resulted in phosphorylation of acetyl CoA carboxylase, which can reduce lipid accumulation in peripheral tissues. In isolated mitochondria, salidroside inhibited respiratory chain complex I and disturbed oxidation/phosphorylation coupling and moderately depolarized the mitochondrial membrane potential, resulting in a transient increase in the AMP/ATP ratio. Conclusions and Implications Salidroside exerts an antidiabetic effect by improving the cellular metabolic flux through the activation of a mitochondria‐related AMPK/PI3K/Akt/GSK3β pathway

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