Epidemiological studies have shown that shift workers are at a greater risk of developing cardiovascular disease which may, in part, be related to metabolic and hormonal changes. Partial sleep deprivation, a common consequence of rotating shift work, has been shown to affect glucose tolerance and insulin sensitivity. The current study investigated the effects of one night of total sleep deprivation, as a proxy for the first night shift, on postprandial glucose, insulin and lipid (triacylglycerols (TAGs) and non-esterified fatty acids (NEFAs)) responses under controlled laboratory conditions in shift workers and non-shift workers. Eleven experienced shift workers (35.7±7.2 years, mean±s.d.) who had worked in shifts for 8.7±5.25 years were matched with 13 non-shift workers who had worked for 32.8±6.4 years. After an adaptation night and a baseline sleep night, volunteers were kept awake for 30.5 h, followed by a nap (4 h) and recovery sleep. Blood samples were taken prior to and after a standard breakfast following baseline sleep, total sleep deprivation and recovery sleep. Basal TAG levels prior to the standard breakfast were significantly lower after sleep deprivation, indicating higher energy expenditure. Basal NEFA levels were significantly lower after recovery sleep. Postprandial insulin and TAG responses were significantly increased, and the NEFA response was decreased after recovery sleep, suggestive of insulin insensitivity. Although there were no overall significant differences between non-shift workers and shift workers, non-shift workers showed significantly higher basal insulin levels, lower basal NEFA levels, and an increased postprandial insulin and a decreased NEFA response after recovery sleep. In future, the reasons for these inter-group differences are to be investigated.

This study was performed to assess the effect of glucocorticoids (dexamethasone) on insulin- and IGF-I-regulated muscle protein metabolism in adult and old rats. Muscle atrophy occurred more rapidly in old rats, and recovery of muscle mass was impaired when compared with adults. Muscle wasting resulted mainly from increased protein breakdown in adult rat but from depressed protein synthesis in the aged animal. Glucocorticoid treatment significantly decreased the stimulatory effect of insulin and IGF-I on muscle protein synthesis in adult rats by 25.9 and 58.1% respectively. In old rats, this effect was even greater, being 49.3 and 100% respectively. With regard to muscle proteolysis, glucocorticoids blunted the anti-proteolytic action of insulin and IGF-I in both age groups. During the recovery period, adult rats reversed the glucocorticoid-induced resistance of muscle protein metabolism within 3 days, at which time old rats still exhibited the decrease in insulin-regulated proteolysis. In conclusion, the higher sensitivity of old rat muscle to glucocorticoids may in part result from the greater modification of the effects of insulin and IGF-I on muscle protein metabolism. These responses to glucocorticoids in old rats may be associated with the emergence of muscle atrophy with advancing age.

Epidemiologic studies have demonstrated that increased prolactin (PRL) exposure raises the risk of invasive estrogen receptor α (ERα)-positive breast cancer in women. However, the mechanism(s) whereby this occurs and the interactions with estrogen itself in this disease remain poorly understood. In order to investigate the role of ovarian hormones in the disease process, we employed a transgenic model neu-related lipocalin (NRL)–PRL in which transgenic PRL is directed to mammary epithelial cells by the PRL- and estrogen-insensitive NRL promoter, mimicking the endogenous PRL expression within the breast observed in women. This high local exposure leads to mammary lesion development and eventually carcinomas. Ovariectomy (ovx), shortly after puberty, did not alter the incidence or latency of PRL-induced mammary carcinomas, consistent with the independence of PRL from circulating estrogens as a risk factor for invasive breast cancer in women. However, chronic estrogen administration to ovx NRL–PRL females decreased the latency of both ERα-positive and -negative tumors. We identified multiple mechanisms that may underlie this observation. Elevated estrogen exposure cooperated with PRL to increase epithelial proliferation and myoepithelial abnormalities, increasing the incidence of preneoplastic lesions. Critical components of the extracellular matrix secreted by the myoepithelium were reduced with age, and transgenic PRL raised transcripts for tenascin-C and maspin, both associated with tumor progression and poor prognosis in subclasses of clinical breast tumors. Mammary pERK1/2 and pAkt, but not phosphorylated Stat5, were markedly elevated by local PRL. Together, these findings indicate that PRL employs multiple mechanisms to promote mammary tumorigenesis.