Prolactin Receptor Is Required for Normal Glucose Homeostasis and Modulation of β-Cell Mass during Pregnancy

Huang, Carol; Snider, Frances; Cross, James C.

doi:10.1210/en.2008-1003

Cited by 272 publications

(327 citation statements)

References 29 publications

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“…Recent reports have demonstrated that prolactin enhanced human b-cell viability (Yamamoto et al 2008) as well as b-cell proliferation through the PI3K signaling pathway (Hü gl & Merger 2007). During pregnancy, both pancreatic b cells and islet endothelial cell display a highly reproducible physiological proliferation that requires the expression of prolactin receptor (Huang et al 2009). From all these observations, reduction of prolactin levels by glucose is important to consider for both islet and endothelial cell functions.…”

Section: Discussionmentioning

confidence: 99%

Glucose inhibits angiogenesis of isolated human pancreatic islets

Dubois

Madec

Mesnier

et al. 2010

Journal of Molecular Endocrinology

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Owing to strong interactions between pancreatic islets and the surrounding capillary network, we hypothesized that high glucose concentrations might affect key angiogenesis factors from isolated human islets, thus contributing to b-cell failure in diabetes. Human islets from eight distinct donors were studied following 96 h in culture in the presence of normal (5 . 5 mmol/l) or high (16 . 7 mmol/l) glucose concentrations. Similar studies were performed with HUVECs. Human angiogenesis-related genes and corresponding proteins were studied by real-time quantitative PCR (RT-qPCR) and protein arrays respectively. Angiogenesis and proliferation assays were also performed with HUVECs under the same culture conditions. RT-qPCR and proteome analysis of human islets incubated with 16 . 7 mM/l glucose revealed a significant decrease in pro-angiogenic factors including vascular endothelial growth factor (VEGF) mRNA by 20% and VEGF protein levels by 42% as well as additional proteins such as fibroblast growth factor-4 by 41%, MMP9 by 18%, monocyte chemoattractant protein-1 by 21%, and prolactin by 25%. In contrast, we observed a 17% increase in thrombospondin-1 (TSP-1, listed as THBS1 in the HUGO database) and a 37% increase in angiotensinogen gene expression levels, but neither angiotensin-converting enzyme nor angiotensin II type 1 receptor gene expression was affected. The amounts of anti-angiogenic proteins such as TSP-1 and serpin B5/maspin were also increased by 70 and 98% respectively as well as endostatin by 63%. Angiogenesis assays of HUVECS in the presence of high glucose concentrations revealed a 30% decrease in tree-like tubular network formation. These data suggest that glucose reduces key factors of islet angiogenesis, which might exacerbate b-cell failure.

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Section: Discussionmentioning

confidence: 99%

Glucose inhibits angiogenesis of isolated human pancreatic islets

Dubois

Madec

Mesnier

et al. 2010

Journal of Molecular Endocrinology

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“…While liver predominantly expresses the short isoform, pancreatic beta cells primarily utilise the long variant of the receptor. Of all tissues examined, expression of PRLRs on rodent beta cells is among the highest and PLs are known to be an important signal for the altered regulation of glucose homeostasis during pregnancy [10,11]. However, a number of interspecies differences exist and these may contribute to the wide variation in reproductive and growth patterns seen between different mammalian families.…”

Section: Introductionmentioning

confidence: 99%

Serotonin competence of mouse beta cells during pregnancy

2016

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Pregnancy is a key mammalian reproductive event in which growth and differentiation of the fetus imposes extra metabolic and hormonal demands on the mother. Its successful outcome depends on major changes in maternal blood circulation, metabolism and endocrine function. One example is the endocrine pancreas, where beta cells undergo a number of changes in pregnancy that result in enhanced functional beta cell mass in order to compensate for the rising metabolic needs for maternal insulin. During the last 5 years, a series of studies have increased our understanding of the molecular events involved in this functional adaptation. In the mouse, a prominent functional change during pregnancy is the capacity of some beta cells to produce serotonin. In this review we will discuss the mechanism and potential effects of pregnancyrelated serotonin production in beta cells, considering functional consequences at the local intra-islet and systemic level.

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“…Preclinical models have demonstrated that prolactin and placentally derived HPL both bind to the prolactin receptor on the b-cells and induce a series of downstream intracellular mediators that ultimately stimulate b-cell growth and proliferation (8)(9)(10)(11). Indeed, the prolactin receptor has been shown to be essential for the expansion of b-cell mass in pregnancy (12,13). Whereas prolactin and HPL are key determinants of this normal physiologic response, the furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) was recently identified as a negative regulator of insulin secretion and hence a mediator of b-cell dysfunction in GDM (14,15).…”

mentioning

confidence: 99%

Maternal Serum Prolactin and Prediction of Postpartum β-Cell Function and Risk of Prediabetes/Diabetes

Retnakaran

Kramer

et al. 2016

Diabetes Care

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OBJECTIVEThe insulin resistance of mid-to late pregnancy poses a physiologic stress test for the pancreatic b-cells, which must respond by markedly increasing their secretion of insulin. This response is achieved through an expansion of b-cell mass induced by the hormones prolactin and human placental lactogen (HPL). Conversely, the furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) has recently emerged as a negative regulator of b-cell function in pregnancy. Given their respective roles in the b-cell response to the stress test of gestation, we hypothesized that antepartum prolactin, HPL, and CMPF may relate to a woman's underlying glucoregulatory physiology and hence to her metabolic status after pregnancy. RESEARCH DESIGN AND METHODSThree hundred and sixty-seven women underwent measurement of fasting serum prolactin, HPL, and CMPF in the late-2nd/early-3rd trimester, followed by an oral glucose tolerance test (OGTT) at 3 months postpartum that enabled assessment of glucose tolerance, insulin sensitivity/resistance, and b-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]). RESULTSThe postpartum OGTT identified 301 women with normal glucose tolerance (NGT) and 66 with prediabetes or diabetes. Serum prolactin in pregnancy was higher in women with postpartum NGT compared with those with postpartum prediabetes/ diabetes (mean 98.2 vs. 80.2 ng/mL, P = 0.0003), whereas HPL and CMPF did not differ between the groups. On multiple linear regression analyses, antepartum prolactin was an independent determinant of postpartum ISSI-2 (b = 0.0016, t = 2.96, P = 0.003). Furthermore, higher serum prolactin in pregnancy independently predicted a lower risk of postpartum prediabetes/diabetes (odds ratio 0.50, 95% CI 0.35-0.72, P = 0.0002). CONCLUSIONSSerum prolactin in pregnancy predicts postpartum b-cell function and risk of prediabetes/diabetes.

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Prolactin Receptor Is Required for Normal Glucose Homeostasis and Modulation of β-Cell Mass during Pregnancy

Cited by 272 publications

References 29 publications

Glucose inhibits angiogenesis of isolated human pancreatic islets

Glucose inhibits angiogenesis of isolated human pancreatic islets

Serotonin competence of mouse beta cells during pregnancy

Maternal Serum Prolactin and Prediction of Postpartum β-Cell Function and Risk of Prediabetes/Diabetes

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