PRLR Regulates Hepatic Insulin Sensitivity in Mice via STAT5

Yu, Junjie; Xiao, Fei; Zhang, Qian; Liu, Bin; Guo, Yinlong; Lv, Ziquan; Xia, Tingting; Chen, Shanghai; Li, Kai; Du, Ying; Guo, Feifan

doi:10.2337/db13-0182

Cited by 49 publications

(34 citation statements)

References 51 publications

(89 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prolactin is a principal determinant of prenatal/postnatal development of pancreatic islet cells, as well as islet adaptation during pregnancy [5, 14, 20, 53]. It is also involved in the regulation of hepatic/adipocytic insulin sensitivity [12, 13], and can indirectly affect hypothalamic dopamine release and energy/glucose homeostasis [54]. In our study, prolactin was inversely correlated with C-peptide and adjusting for C-peptide attenuated the association between prolactin and type 2 diabetes (particularly for bioactive prolactin).…”

Section: Discussionmentioning

confidence: 99%

Circulating prolactin concentrations and risk of type 2 diabetes in US women

Rice

Huang

et al. 2018

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis Prolactin, a multifunctional hormone, is involved in regulating insulin sensitivity and glucose homeostasis in experimental studies. However, whether circulating concentrations of prolactin are associated with risk of type 2 diabetes remains uncertain. Methods We analysed the prospective relationship between circulating prolactin concentrations and type 2 diabetes risk in the Nurses’ Health Study (NHS) and NHSII with up to 22 years of follow-up. Total plasma prolactin was measured using immunoassay in 8615 women free of type 2 diabetes and cardiovascular disease at baseline blood collection (NHS 1989–1990; NHSII 1996–1999) and a subset of 998 NHS women providing a second blood sample during 2000–2002. Baseline bioactive prolactin was measured in a subset of 2478 women using the Nb2 bioassay. HRs were estimated using Cox regression. Results A total of 699 incident type 2 diabetes cases were documented during 156,140 person- years of follow-up. Total plasma prolactin levels were inversely associated with type 2 diabetes risk; the multivariable HR comparing the highest with the lowest quartile was 0.73 (95% CI 0.55, 0.95; ptrend=0.02). The associations were similar by menopausal status and other risk factors (pinteraction>0.70). Additional adjustment for sex and growth hormones, adiponectin, and inflammatory and insulin markers did not significantly alter the results. The association of plasma bioactive prolactin with type 2 diabetes risk was non-significantly stronger than that of total prolactin (HR comparing extreme quartiles, 0.53 vs 0.81 among the subset of 2478 women, pdifference=0.11). The inverse association of total prolactin with type 2 diabetes was significant during the first 9 years after blood draw but waned linearly with time, whereas for bioactive prolactin, the inverse relationship persisted for a longer follow-up time after blood draw. Conclusions/interpretation A normally high circulating total prolactin concentration was associated with a lower type 2 diabetes risk within 9–10 years of follow-up since blood draw in US women. Our findings are consistent with experimental evidence, suggesting that among healthy women, prolactin within the biologically normal range may play a protective role in the pathogenesis of type 2 diabetes.

show abstract

Section: Discussionmentioning

confidence: 99%

Circulating prolactin concentrations and risk of type 2 diabetes in US women

Rice

Huang

et al. 2018

Diabetologia

View full text Add to dashboard Cite

show abstract

“…To evaluate whether PRL treatment in mothers or offspring was acting on PRL target tissues of the pups, we evaluated the phosphorylation of STAT5, a canonical signaling transcription factor downstream of the PRL receptor, in livers from offspring on d 21 of lactation. Liver was used because this tissue has one of the highest expression of PRL receptors (44); it is a relevant metabolic tissue and a direct target of PRL actions (45). We observed that STAT5 phosphorylation decreased in livers of pups from HFD‐fed dams compared with those from CD‐fed mothers, suggesting that even if serum PRL levels are similar in the pups from both groups (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In adult animals, PRL stimulates liver insulin sensitivity. Knockdown of the liver PRL receptor leads to insulin resistance, whereas overexpression of the PRL receptor promotes insulin sensitivity, and the PRL effect is mediated by STAT5, a canonical PRL signaling molecule (45). Additional support for the direct actions of milk PRL in the offspring derive from the finding that PRL treatment in the offspring or in the mothers increases STAT5 phosphorylation in the liver of the offspring, whereas its phosphorylation is reduced in offspring from HFD‐fed dams compared with offspring from CD dams.…”

Section: Discussionmentioning

confidence: 99%

“…Bars without lines are rat PRL (endogenous) levels quantified by radioimmunoassay; lined bars are ovine PRL levels delivered by pumps and measured by using the Nb2 assay. C) Milk yield on d 8 and 19 of lactation of dams fed with CD or HFD in the absence or presence of osmotic minipumps delivering PRL (HFD + PRL) during lactation (n =[40][41][42][43][44][45][46][47][48]. Data are means 6 SEM.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Impaired prolactin actions mediate altered offspring metabolism induced by maternal high‐fat feeding during lactation

et al. 2018

View full text Add to dashboard Cite

Maternal diet during lactation affects offspring metabolic health throughout life. Prolactin (PRL) is present in high quantities in maternal milk; however, the effects of milk PRL on the offspring remain poorly characterized. In this study, we evaluated whether feeding a high-fat diet (HFD) to rats during lactation alters PRL, both in the mother's serum and in milk, and whether this factor contributes to HFD-induced metabolic dysfunction in the offspring. Maternal HFD resulted in decreased PRL levels in milk (but not in serum), reduced mammary gland (MG) PRL receptor expression, and altered MG structure and function. Offspring from HFD-fed dams had increased body weight and adiposity, and developed fatty liver, hyperinsulinemia, and insulin resistance at weaning. Increasing PRL levels in the HFD-fed mothers by subcutaneous osmotic minipumps releasing PRL normalized MG function and PRL levels in milk. Moreover, PRL treatment in HFD-fed mothers, or directly in their pups via oral PRL administration, increased liver STAT5 phosphorylation, reduced visceral adiposity, ameliorated fatty liver, and improved insulin sensitivity in offspring. Our results show that HFD impairs PRL actions during lactation to negatively affect MG physiology and directly impair offspring metabolism.-De los Ríos, E. A., Ruiz-Herrera, X., Tinoco-Pantoja, V., López-Barrera, F., Martínez de la Escalera, G., Clapp, C., Macotela, Y. Impaired prolactin actions mediate altered offspring metabolism induced by maternal high-fat feeding during lactation.

show abstract

“…It is important to study whether the changes in the dietary protein/carbohydrate ratio may affect the expression of SNAT2 not only in the mammary gland but also in other tissues such as the adipose tissue and liver. It has been demonstrated that the prolactin receptor is present in these tissues among others [23][24][25][26][27]. However, there is no knowledge whether during lactation the SNAT2 gene is regulated in a similar fashion in these tissues compared with the mammary gland.…”

Section: Introductionmentioning

confidence: 99%

Prolactin and the dietary protein/carbohydrate ratio regulate the expression of SNAT2 amino acid transporter in the mammary gland during lactation

Velázquez-Villegas

López-Barradas

Torres

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

View full text Add to dashboard Cite

The sodium coupled neutral amino acid transporter 2 (SNAT2/SAT2/ATA2) is expressed in the mammary gland (MG) and plays an important role in the uptake of alanine and glutamine which are the most abundant amino acids transported into this tissue during lactation. Thus, the aim of this study was to assess the amount and localization of SNAT2 before delivery and during lactation in rat MG, and to evaluate whether prolactin and the dietary protein/carbohydrate ratio might influence SNAT2 expression in the MG, liver and adipose tissue during lactation. Our results showed that SNAT2 protein abundance in the MG increased during lactation and this increase was maintained along this period, while 24 h after weaning it tended to decrease. To study the effect of prolactin on SNAT2 expression, we incubated MG explants or T47D cells transfected with the SNAT2 promoter with prolactin, and we observed in both studies an increase in the SNAT2 expression or promoter activity. Consumption of a high-protein/low carbohydrate diet increased prolactin concentration, with a concomitant increase in SNAT2 expression not only in the MG during lactation, but also in the liver and adipose tissue. There was a correlation between SNAT2 expression and serum prolactin levels depending on the amount of dietary protein/carbohydrate ratio consumed. These findings suggest that prolactin actively supports lactation providing amino acids to the gland through SNAT2 for the synthesis of milk proteins.

show abstract

PRLR Regulates Hepatic Insulin Sensitivity in Mice via STAT5

Cited by 49 publications

References 51 publications

Circulating prolactin concentrations and risk of type 2 diabetes in US women

Circulating prolactin concentrations and risk of type 2 diabetes in US women

Impaired prolactin actions mediate altered offspring metabolism induced by maternal high‐fat feeding during lactation

Prolactin and the dietary protein/carbohydrate ratio regulate the expression of SNAT2 amino acid transporter in the mammary gland during lactation

Contact Info

Product

Resources

About