| 1. |
- Adhikari, Deepak, et al.
(författare)
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The regulation of maturation promoting factor during prophase I arrest and meiotic entry in mammalian oocytes
- 2014
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207. ; 382:1, s. 480-487
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Tidskriftsartikel (refereegranskat)abstract
- Mammalian oocytes arrest at prophase of meiosis I at around birth and they remain arrested at this stage until puberty when the preovulatory surge of luteinizing hormone (LH) causes ovulation. Prophase I arrest in the immature oocyte results from the maintenance of low activity of maturation promoting factor (MPF), which consists of a catalytic subunit (CDK1) and regulatory subunit (cyclin B1). Phosphorylation-mediated inactivation of CDK1 and constant degradation of cyclin B1 keep MPF activity low during prophase I arrest. LH-mediated signaling manipulates a vast array of molecules to activate CDK1. Active CDK1 not only phosphorylates different meiotic phosphoproteins during the resumption of meiosis but also inhibits their rapid dephosphorylation by inhibiting the activities of CDK1 antagonizing protein phosphatases (PPs). In this way, CDK1 both phosphorylates its substrates and protects them from being dephosphorylated. Accumulating evidence suggests thatthe net MPF activity that drives the resumption of meiosis in oocytes depends on the activation status of CDK1 antagonizing PPs. This review aims to provide a summary of the current understanding of the signaling pathways involved in regulating MPF activity during prophase I arrest and reentry into meiosis of mammalian oocytes. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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| 2. |
- Andersson, Sofia A, et al.
(författare)
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Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes.
- 2012
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 364:1-2, s. 36-45
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Tidskriftsartikel (refereegranskat)abstract
- Reduced insulin release has been linked to defect exocytosis in β-cells. However, whether expression of genes suggested to be involved in the exocytotic process (exocytotic genes) is altered in pancreatic islets from patients with type 2 diabetes (T2D), and correlate to insulin secretion, needs to be further investigated. Analysing expression levels of 23 exocytotic genes using microarray revealed reduced expression of five genes in human T2D islets (χ(2)=13.25; p<0.001). Gene expression of STX1A, SYT4, SYT7, SYT11, SYT13, SNAP25 and STXBP1 correlated negatively to in vivo measurements of HbA1c levels and positively to glucose stimulated insulin secretion (GSIS) in vitro in human islets. STX1A, SYT4 and SYT11 protein levels correspondingly decreased in human T2D islets. Moreover, silencing of SYT4 and SYT13 reduced GSIS in INS1-832/13 cells. Our data support that reduced expression of exocytotic genes contributes to impaired insulin secretion, and suggest decreased expression of these genes as part of T2D pathogenesis.
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| 3. |
- Balhuizen, Alexander, et al.
(författare)
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Activation of G protein-coupled receptor 30 modulates hormone secretion and counteracts cytokine-induced apoptosis in pancreatic islets of female mice.
- 2010
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 320, s. 16-24
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Tidskriftsartikel (refereegranskat)abstract
- The role of the newly discovered estrogen receptor GPR30 in islet physiology and pathophysiology is unclear. We examined GPR30 expression in relation to hormone secretion and possible anti-apoptotic effects in isolated mouse islets using the synthetic GPR30 ligand G-1. The mRNA and protein expression of GPR30 was analyzed by qPCR, Western blot and confocal microscopy. Hormone secretion and cAMP content were determined with RIA and apoptosis in islet cells with the Annexin-V method. GPR30 mRNA and protein expression was markedly higher in islets from females compared to male. This gender difference was not found for the genomic estrogen receptors ERalpha and ERbeta, the ERalpha expression being 10-fold higher than ERbeta in both genders. Confocal microscopy revealed abounden GPR30 expression in insulin, glucagon and somatostatin cells. Dose-response studies of G-1 vs 17beta-estradiol in isolated islets at 1 or 12mM glucose showed an almost identical pattern in that both compounds increased insulin and inhibited glucagon and somatostatin secretion. ICI-182,780 and EM-652, potent antagonists of the 17beta-estradiol receptors (ERalpha and ERbeta) did not influence the amplifying effect of G-1 or 17beta-estradiol on cAMP content or insulin secretion from isolated islets. Cytokine-induced (IL-1beta+TNFalpha+INFgamma) apoptosis in islets, cultured for 24h at 5mM glucose, was almost abolished by G-1 or 17beta-estradiol treatment. Addition of ICI-182,780 or EM-652 did not affect this beneficial effect of G-1 or 17beta-estradiol. Taken together, our findings show that GPR30 is expressed in most islet endocrine cells. The synthetic GPR30 ligand G-1 mimics the non-genomic effects of 17beta-estradiol on islet hormone secretion, cAMP content in islets and its anti-apoptotic effects. G-1 or analogs thereof might be new potential candidates in the therapeutic strategy for type 2 diabetes in women.
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| 4. |
- Banerjee, Meenal, et al.
(författare)
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Proliferation and plasticity of human beta cells on physiologically occurring laminin isoforms
- 2012
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 355:1, s. 78-86
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Tidskriftsartikel (refereegranskat)abstract
- We have previously characterized the molecular composition of human islet basement membranes and shown that human beta cells bind to laminin 511 (LM511) through integrin alpha 3 beta 1 and Lutheran glycoprotein. We have now investigated the impact of physical contact between cultured human beta cells and the laminin isoforms occurring in their natural niche. Human islet preparations derived from 15 donors were used, beta cells and duct cells were purified by magnetic sorting. Overall beta-cell proliferation was low or undetectable. However, in many experiments the only proliferating beta cells were detected in contact with the laminin isoforms that are found in the human islets in vivo (511 and 411). Purified ductal and beta cells underwent epithelial-mesenchymal transition (EMT). LM511 partially blocked this dedifferentiation of purified beta cells, and did not affect purified duct cells. Interactions with the surrounding basement membrane are important for the growth and function of human beta cells. However, only a very limited level of beta-cell proliferation can be induced by exogenous factors. LM511 may be a useful substrate for human beta-cell maintenance in vitro.
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| 5. |
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| 6. |
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| 7. |
- Brokken, Leon, et al.
(författare)
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Association of polymorphisms in genes encoding hormone receptors ESR1, ESR2 and LHCGR with the risk and clinical features of testicular germ cell cancer.
- 2012
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 351:2, s. 279-285
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Tidskriftsartikel (refereegranskat)abstract
- Testicular germ cell cancer (TGCC) is the most common malignancy in young men. Genetic variants known to be associated with risk of TGCC only partially account for the observed familial risks. We aimed to identify additional polymorphisms associated with risk as well as histological and clinical features of TGCC in 367 patients and 214 controls. Polymorphisms in ESR2 (rs1256063; OR=0.53, 95% CI: 0.35-0.79) and LHCGR (rs4597581; OR=0.68, 95% CI: 0.51-0.89, and rs4953617; OR=1.88, 95% CI: 1.21-2.94) associated with risk of TGCC. Polymorphisms in ESR1 (rs9397080; OR=1.85, 95% CI: 1.18-2.91) and LHCGR (rs7371084; OR=2.37, 95% CI: 1.26-4.49) associated with risk of seminoma and metastasis, respectively. SNPs in ESR1 (rs9397080) and LHCGR (rs7371084) were predictors of higher LH levels and higher androgen sensitivity index in healthy subjects. The results suggest that polymorphisms in ESR1, ESR2 and LHCGR contribute to the risk of developing TGCC, histological subtype, and risk to metastasis.
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| 8. |
- Brokken, Leon, et al.
(författare)
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Non-linear association between androgen receptor CAG and GGN repeat lengths and reproductive parameters in fertile European and Inuit men.
- 2013
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 370:1-2, s. 163-171
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Tidskriftsartikel (refereegranskat)abstract
- Recently the dogma that there is an inverse linear association between androgen receptor (AR) CAG and GGN polymorphisms and receptor activity has been challenged. We analysed the pattern of association between 21 male reproductive phenotypes and AR CAG/GGN repeat lengths in 557 proven-fertile men. A linear association was only found between sperm DNA fragmentation index (DFI) and CAG length, and between inhibin B and GGN length. Men with longer CAG then the reference (22-24), had higher oestradiol levels, whereas men with shorter CAG stretches had a higher DFI and a higher proportion of Fas-positive germ cells. Subjects with either short or long CAG had increased seminal levels of prostate-specific antigen and neutral α-glucosidase activity. Compared to men with the median GGN length of 23, those with shorter GGN repeats had higher levels of inhibin B, higher proportions of normal and progressive sperm, and a higher fraction of Fas-positive sperm, while men with longer GGN had higher oestradiol levels. These data indicate that at least for some markers of male reproductive function the association with CAG or GGN repeat length is curvilinear.
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| 9. |
- Bäck, Karolina, et al.
(författare)
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Differential effects of IGF-I, IGF-II and insulin in human preadipocytes and adipocytes - Role of insulin and IGF-I receptors
- 2011
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier Science B.V., Amsterdam.. - 0303-7207 .- 1872-8057. ; 339:02-jan, s. 130-135
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Tidskriftsartikel (refereegranskat)abstract
- We compared insulin and IGF effects in adipocytes expressing IR (insulin receptors), and preadipocytes expressing IR and IGF-IR (IGF-I receptors). Treatment of adipocytes with insulin, IGF-II or IGF-I resulted in phosphorylation of IR. Order of potency was insulin greater thanIGF-IIgreater than IGF-I. In preadipocytes IR, IGF-IR and insulin/IGF-I hybrid receptors (HR) were detected. Treatment of preadipocytes with IGF-I and IGF-II 10(-8) M resulted in activation of IGF-IR and IR whereas insulin was more potent in activating IR, with no effect on IGF-IR. In adipocytes glucose transport was 100-fold more sensitive to insulin than to IGFs and the maximal effect was higher with insulin. In preadipocytes glucose accumulation and DNA synthesis was equally sensitive to insulin and IGFs but the maximal effect was higher with IGF-I. In conclusion, insulin and IGF-I activate their cognate receptors and IGF-I also HR. IGF-II activates IR, IGF-IR and HR. Insulin and IGF-I are partial agonists to each others receptors.
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| 10. |
- Cansby, Emmelie, 1984, et al.
(författare)
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Partial hepatic resistance to IL-6-induced inflammation develops in type 2 diabetic mice, while the anti-inflammatory effect of AMPK is maintained
- 2014
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207. ; 393:1-2, s. 143-151
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-6 (IL-6) induces hepatic inflammation and insulin resistance, and therapeutic strategies to counteract the IL-6 action in liver are of high interest. In this study, we demonstrate that acute treatment with AMP-activated protein kinase (AMPK) agonists AICAR and metformin efficiently repressed IL-6-induced hepatic proinflammatory gene expression and activation of STAT3 in a mouse model of diet-induced type 2 diabetes, bringing it back to basal nonstimulated level. Surprisingly, the inflammatory response in liver induced by IL-6 administration in vivo was markedly blunted in the mice fed a high-fat diet, compared to lean chow-fed controls, while this difference was not replicated in vitro in primary hepatocytes derived from these two groups of mice. In summary, our work reveals that partial hepatic IL-6 resistance develops in the mouse model of type 2 diabetes, while the anti-inflammatory action of AMPK is maintained. Systemic factors, rather than differences in intracellular IL-6 receptor signaling, are likely mediating the relative impairment in IL-6 effect.
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