Decreased plasma chemerin levels in women with gestational diabetes mellitus.

AIMS: To evaluate fasting and post-prandial serum chemerin levels in pregnant women with and without gestational diabetes, and again following delivery when normal glucose homeostasis is re-established. METHODS: Chemerin levels were measured in serum from nine women with gestational diabetes, and from eight age- and BMI-matched pregnant women with normal glucose tolerance during two meal tests: in the third trimester and 3-4 months post partum. All women with gestational diabetes re-established normal glucose tolerance after delivery. RESULTS: Meal intake did not affect serum chemerin levels. The group with gestational diabetes had lower mean serum chemerin levels during the third trimester compared with the group with normal glucose tolerance (28 ± 1.3 vs. 88 ± 3.5 ng/ml, P < 0.0001). In the group with normal glucose tolerance, mean serum chemerin levels decreased significantly post partum to 57 ± 2.8 ng/ml (P = 0.0001), but remained significantly (P = 0.0003) higher than post-partum levels in the group with gestational diabetes (31 ± 1.9 ng/ml), which did not differ significantly from third trimester levels (P = 0.31). CONCLUSIONS: Normal pregnancy is associated with increased circulating chemerin levels, which may act to reduce pregnancy-induced insulin resistance and prevent glucose intolerance. Women with gestational diabetes, however, have severely reduced chemerin levels that remain low after delivery, which may contribute to the insulin resistance, glucose intolerance and high type 2 diabetes risk associated with gestational diabetes.

Neuroendocrine and endocrine dysfunction in the hyperinsulinemic PCOS patient: the role of metformin.

Metformin is a widely used and extensively studied insulin sensitising drug for the treatment of women with polycystic ovary syndrome (PCOS), with various actions in tissues responding to insulin that include the liver, skeletal muscle, adipose tissue, the endothelium of blood vessels, and the ovaries. Treatment of PCOS women with metformin has been shown to reduce fasting glucose levels, blood pressure, and serum androgens; further effects of metformin in women with PCOS may include direct effects on the central nervous system; and indirect effects via the modification of gut hormone and adipokine synthesis and/or secretion. A number of "novel" adipokines and metabolic factors have been recently identified which may play a role both in the pathogenesis and the treatment of women with PCOS. We here discuss recent advances in the area, with a focus on neuroendocrine and endocrine dysfunctions in women with PCOS and the potential role of metformin in this context.

Phosphoprotein enriched in diabetes gene product (Ped/pea-15) is increased in omental adipose tissue of women with the polycystic ovary syndrome: ex vivo regulation of ped/pea-15 by glucose, insulin and metformin.

Polycystic ovary syndrome (PCOS), the commonest endocrine disorder in women, is characterized by an altered steroid milieu and is associated with insulin resistance and type 2 diabetes mellitus (T2DM). Phosphoprotein enriched in diabetes gene product (Ped/pea-15) regulates glucose metabolism and is increased in T2DM. Our novel data indicate that Ped/pea-15 mRNA expression and protein levels are significantly increased in omental adipose tissue (AT) from PCOS women compared to matched controls (p < 0.01); Ped/pea-15 levels in subcutaneous AT were not significantly different. Furthermore, Ped/pea-15 mRNA expression and protein levels were higher in omental compared to subcutaneous AT in PCOS subjects (p < 0.01); however, in control subjects, this was not significant. Glucose was predictive of omental AT Ped/pea-15 mRNA expression (p = 0.045). Importantly, glucose and insulin increased whereas metformin significantly decreased Ped/pea-15 levels in human omental AT explants. Our findings should serve to promote further research on Ped/pea-15 biology.

Home administration of lanreotide Autogel by patients with acromegaly, or their partners, is safe and effective.

OBJECTIVE: The introduction of ready-to-use lanreotide Autogel has presented the possibility of patients receiving their acromegaly treatment at home. The objective of this study was to assess the ability of patients (or their partners) to administer repeat, unsupervised, injections of lanreotide Autogel without compromising efficacy or safety. DESIGN: Multicentre (10 UK regional endocrine centres), open-label, nonrandomised, controlled study. Patients elected either to receive/administer unsupervised home injections after injection technique training (Test group) or continued to receive injections from a healthcare professional (Control group). Patients received monthly injections of lanreotide Autogel at their established dose. Effects were monitored for up to 40 weeks. PATIENTS: Thirty patients (15 per treatment group) with acromegaly treated with a stable dose of lanreotide Autogel (60, 90 or 120 mg) for > or = 4 months before screening. Measurements The main outcome measure was the proportion of patients/partners who successfully administered injections throughout the study. RESULTS: All Test group patients/partners qualified to administer injections. Fourteen of 15 patients fulfilled all criteria for successful administration of unsupervised injections (95% confidence interval, 70%-99%). Fourteen of 15 Test and 14/15 Control patients maintained growth hormone and IGF-1 control. Local injection tolerability was good for both treatment groups, and safety profiles were similar. All Test group patients continued with unsupervised injections after the study. CONCLUSIONS: Patients with acromegaly or their partners were able to administer lanreotide Autogel injections with no detrimental effect on efficacy and safety; therefore, unsupervised home injections are a viable alternative to healthcare professional injections for suitably motivated patients.

Increased circulating levels of matrix metalloproteinase-2 and -9 in women with the polycystic ovary syndrome.

INTRODUCTION: Matrix metalloproteinases (MMPs) have been implicated in various pathological processes including inflammatory response, cardiovascular disease, and recently also in ovarian dysfunction. Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age and is characterized by chronic anovulation, insulin resistance, and increased prevalence of cardiovascular risk factors. Circulating levels of MMPs and their tissue inhibitors (TIMPs) so far have not been assessed in the PCOS. MATERIALS AND METHODS: Serum levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured in 23 women with PCOS [age (mean +/- sd), 30.5 +/- 6.7 yr; body mass index, 35.8 +/- 7.5 kg/m2] and 22 healthy, regularly menstruating women (age, 29.4 +/- 5.6; body mass index, 31.7 +/- 9.2 kg/m2). RESULTS: Women with PCOS had significantly higher concentrations of MMP-2 (999.8 +/- 155 vs. 521.8 +/- 242 ng/ml; P < 0.001), MMP-9 (592.4 +/- 279 vs. 345 +/- 309; P = 0.007), and TIMP-1 levels (823.8 +/- 145 vs. 692 +/- 210 ng/ml; P = 0.02) than control healthy women. There was no difference in TIMP-2 levels (47.3 +/- 30 vs. 44.4 +/- 39.7 ng/ml; P = 0.21) between women with PCOS and controls. CONCLUSIONS: Obese women with PCOS have elevated serum concentrations of MMP-2 and -9. It might be hypothesized that elevated MMP concentrations may be related to increased cardiovascular risk in PCOS and/or menstrual irregularities associated with this syndrome.

Reductions of circulating matrix metalloproteinase 2 and vascular endothelial growth factor levels after treatment with pegvisomant in subjects with acromegaly.

BACKGROUND: Vascular endothelial growth factor (VEGF) is involved in activation of the matrix metalloproteinase (MMP) system; the latter is implicated in atherosclerosis and cardiovascular disease. Patients with acromegaly have reduced life expectancy primarily due to cardiac disease. AIM: This study assessed plasma MMPs and VEGF levels in patients with active acromegaly (IGF-I > 130% upper limit of normal), and on treatment with pegvisomant. SUBJECTS AND METHODS: Twenty patients [nine female, mean age 56.1 +/- 13.8 yr (mean +/- sd)] were studied at baseline and on pegvisomant therapy and compared with data from 25 healthy volunteers (12 female; 56.6 +/- 14.2 yr). Plasma MMP-2, MMP-9, and VEGF levels were measured. RESULTS: Serum IGF-I fell from a baseline (mean +/- sd) level of 620.1 +/- 209.3 ng/ml to 237.5 +/- 118.5 ng/ml on pegvisomant (doses 10-60 mg; P < 0.001). MMP-2 levels at baseline were significantly higher in patients compared with healthy controls (380.7 +/- 204.8 vs. 207.4 +/- 62.6 ng/ml; P < 0.001), but with treatment a significant reduction in MMP-2 [380.7 +/- 204.8 vs. 203.0 +/- 77.4 ng/ml; P < 0.001] and VEGF (283.4 +/- 233.6 vs. 229.1 +/- 157.4 pg/ml; P = 0.008) was noted. There was no significant difference in MMP-9 levels between patients and controls at baseline (797.5 +/- 142.1 vs. 788.3 +/- 218.0 ng/ml; P = 0.87) or between baseline and posttreatment levels (797.5 +/- 142.1 vs. 780.0 +/- 214 ng/ml; P = 0.76). CONCLUSIONS: Our novel data demonstrate that treatment of acromegaly with pegvisomant leads to reductions in MMP-2 and VEGF concentrations. Further studies are required to determine the significance of these findings with relation to cardiac disease.

Effects of hormone replacement therapy type and route of administration on plasma matrix metalloproteinases and their tissue inhibitors in postmenopausal women.

BACKGROUND: Matrix metalloproteinases (MMPs) are implicated in numerous disease states including cardiovascular disease and cancer. Because recent studies have shown a detrimental effect of hormone replacement therapy on cardiovascular disease and breast cancer, we investigated whether there are any differences in the concentrations of MMPs and their tissue inhibitors (TIMPs) in women receiving various forms of postmenopausal therapy. MATERIAL AND METHODS: A total of 195 healthy postmenopausal women were assessed: 46 were taking tibolone, 47 were taking transdermal estradiol, 46 were taking conjugated equine estrogens (CEE), and 56 were not taking any menopausal therapy (CTR). Plasma levels of MMP-2 and -9 and TIMP-1 and TIMP-2 were measured by ELISA methods. RESULTS: MMP-9 levels were significantly higher in the CEE group in comparison with healthy women not receiving menopausal therapy (P < 0.05). In contrast, MMP-9 levels in the tibolone group were significantly lower than in any other group (P < 0.01, compared with transdermal estradiol and CTR, and P < 0.001, compared with CEE). MMP-9 to TIMP-1 ratio was also significantly higher in the CEE, compared with CTR (P < 0.05), and lower in the tibolone group (P < 0.01, compared with all groups). MMP-2 levels were higher in the CEE group, compared with healthy women not receiving any menopausal therapy, and women taking tibolone (P < 0.05). CONCLUSIONS: Our study demonstrates differential effects of various forms of postmenopausal therapy on serum levels of MMP-9 and MMP-2. It remains to be established whether these differences might be associated with differences in risks of cardiovascular disease and cancer in these women.

Orexin receptor expression in human adipose tissue: effects of orexin-A and orexin-B.

Orexin-A and orexin-B, via their receptors orexin-1 receptor (OX1R) and orexin-2 receptor (OX2R) have been shown to play a role in the regulation of feeding, body weight, and energy expenditure. Adipose tissue also contributes significantly to the maintenance of body weight by interacting with a complex array of bioactive peptides; however, there are no data as yet on the expression of orexin components in adipose tissue. We, therefore, analyzed the expression of OX1R and OX2R in human adipose tissue and determined functional responses to orexin-A and orexin-B. OX1R and OX2R mRNA expression was detected in subcutaneous (s.c.) and omental adipose tissue and in isolated adipocytes. Protein for OX1R and OX2R was also detected in whole adipose tissue sections and lysates. Treatment with orexin-A, and orexin-B (100 nM, 24 h) resulted in a significant increase in peroxisome proliferator-activated receptors gamma-2 mRNA expression in s.c. adipose tissue (P < 0.05). Hormone sensitive lipase mRNA was significantly reduced in omental adipose tissue with orexin-A and orexin-B treatment (P < 0.05). Glycerol release from omental adipose tissue was also significantly reduced with orexin-A treatment (P < 0.05). These findings demonstrate for the first time the presence of functional orexin receptors in human adipose tissue and suggest a role for orexins in adipose tissue metabolism and adipogenesis.

Novel placental expression of 2,3-bisphosphoglycerate mutase.

2,3-Bisphosphoglycerate mutase (2,3-BPGM), an erythroid-expressed enzyme, synthesises 2,3-bisphosphoglycerate (2,3-BPG), the allosteric modulator of haemoglobin. This ligand has a higher affinity for adult haemoglobin than for fetal haemoglobin and differential binding of it facilitates transfer of oxygen between adult and fetal blood by lowering the affinity of adult haemoglobin for oxygen. This paper reports the discovery that 2,3-BPGM is synthesised in non-erythroid cells of the human placenta. Western blot analysis of placental extracts revealed high levels of 2,3-BPGM in the human placenta. Immunohistochemical staining and in situ hybridisation experiments indicated that abundant 2,3-BPGM is present in the syncytiotrophoblast layer of the placental villi at the feto-maternal interface. A cytochemical staining technique showed that the placental 2,3-BPGM is active, indicating that 2,3-BPG is synthesised in the outermost cells of the placenta. These observations demonstrate an unexpected and abundant presence of an enzyme key to oxygen release from adult haemoglobin, at the interface between maternal and fetal circulations.

Urocortin, but not corticotropin-releasing hormone (CRH), activates the mitogen-activated protein kinase signal transduction pathway in human pregnant myometrium: an effect mediated via R1alpha and R2beta CRH receptor subtypes and stimulation of Gq-proteins.

CRH and CRH-related peptides such as urocortin mediate their actions in the human myometrium via activation of two distinct classes of CRH receptors, R1 and R2. These heptahelical receptors are able to stimulate a number of different intracellular signals; one key mediator of G protein-activated intracellular signaling is the cascade of p42/p44, mitogen-activated protein kinase (MAPK). We therefore hypothesized that activation of MAPK might mediate CRH and or/urocortin actions in the myometrium. In cultured human pregnant myometrial cells, urocortin but not CRH was able to induce MAPK phosphorylation and activation, suggesting that in the human myometrium these two peptides have distinct actions and biological roles. To identify the particular receptor subtypes mediating this phenomenon, all known CRH receptors present in the human myometrial cells were stably expressed individually in HEK293 and CHO cells, and their ability to activate MAPK was tested. The R1alpha and R2beta, but not the R1beta, R1c, or R1d, receptor subtypes were able to mediate urocortin-induced MAPK activation. The signaling components were further investigated; activation of Gs, Go, or Gi proteins did not appear to be involved, but activation of Gq with subsequent production of inositol triphosphates (IP3) and protein kinase C (PKC) activation correlated with MAPK phosphorylation. Studies on Gq protein activation using [alpha-32P]-GTP-gamma-azidoanilide and IP3 production in cells expressing the R1alpha or R2beta CRH receptors demonstrated that urocortin was 10 times more potent than CRH. Moreover, urocortin (UCN) generated peak responses that were 50-70% greater than CRH in activating the Gq protein and stimulating IP3 production. In conclusion, UCN acting thought multiple receptor subtypes can stimulate myometrial MAPK via induction of the Gq/phospholipase C/IP3/PKC pathway, whereas CRH-induced activation of this pathway appears to be insufficient to achieve MAPK activation.

A novel spliced variant of the type 1 corticotropin-releasing hormone receptor with a deletion in the seventh transmembrane domain present in the human pregnant term myometrium and fetal membranes.

CRH exerts its actions via activation of specific G protein-coupled receptors, which exist in two types, CRH-R1 and CRH-R2, and arise from different genes with multiple spliced variants. RT-PCR amplification of CRH receptor sequences from human myometrium and fetal membranes yielded cDNAs that encode a novel CRH-R type 1 spliced variant. This variant (CRH-R1d) is present in the human pregnant myometrium at term only, which suggests a physiologically important role at the end of human pregnancy and labor. The amino acid sequence of CRH-R1d is identical to the CRH-R1alpha receptor except that it contains an exon deletion resulting in the absence of 14 amino acids in the predicted seventh transmembrane domain. Binding studies in HEK-293 cells stably expressing the CRH-R1d or CRH-R1alpha receptors revealed that the deletion does not change the binding characteristics of the variant receptor. In contrast, studies on the G protein activation demonstrated that CRH-R1d is not well coupled to the four subtypes of G proteins (G(s), G(i), G(o), G(q)) that CRH-R1alpha can activate. These data suggest that although the deleted segment is not important for CRH binding, it plays a crucial role in CRH receptor signal transduction. Second messenger studies of the variant receptor showed that CRH and CRH-like peptides can stimulate the adenylate cyclase system, with reduced sensitivity and potency by 10-fold compared with the CRH-R1alpha. Furthermore, CRH failed to stimulate inositol trisphosphate production. Coexpression studies between the CRH-R1d or CRH-R1alpha showed that this receptor does not play a role as a dominant negative receptor for CRH.

Severe paraneoplastic hypoglycemia secondary to a gastrointestinal stromal tumour masquerading as a stroke.

UNLABELLED: We report the case of a 70-year-old previously healthy female who presented acutely to the Accident and Emergency department with left-sided vasomotor symptoms including reduced muscle tone, weakness upon walking and slurred speech. Physical examination confirmed hemiparesis with VIIth nerve palsy and profound hepatomegaly. A random glucose was low at 1.7 mmol/l, which upon correction resolved her symptoms. In hindsight, the patient recalled having had similar episodes periodically over the past 3 months to which she did not give much attention. While hospitalized, she continued having episodes of symptomatic hypoglycaemia during most nights, requiring treatment with i.v. dextrose and/or glucagon. Blood tests including insulin and C-peptide were invariably suppressed, in correlation with low glucose. A Synacthen stimulation test was normal (Cort (0') 390 nmol/l, Cort (30') 773 nmol/l). A computed tomography scan showed multiple lobulated masses in the abdomen, liver and pelvis. An ultrasound guided biopsy of one of the pelvic masses was performed. Immunohistochemistry supported the diagnosis of a gastrointestinal stromal tumour (GIST) positive for CD34 and CD117. A diagnosis of a non islet cell tumour hypoglycaemia (NICTH) secondary to an IGF2 secreting GIST was confirmed with further biochemical investigations (IGF2=96.5 nmol/l; IGF2:IGF1 ratio 18.9, ULN <10). Treatment with growth hormone resolved the patient's hypoglycaemic symptoms and subsequent targeted therapy with Imatinib was successful in controlling disease progression over an 8-year observation period. LEARNING POINTS: NICTH can be a rare complication of GISTs that may manifest with severe hypoglycaemia and neuroglucopenic symptoms.NICTH can masquerade as other pathologies thus causing diagnostic confusion.Histological confirmation of GIST induced NICTH and exclusion of other conditions causing hypoglycaemia is essential.Mutational analysis of GISTs should be carried out in all cases as it guides treatment decision.Tailored management of hypoglycaemia, in this case using growth hormone and targeted cyto-reductive therapy, minimizes the risk of possible life-threatening complications.

Expression of orexin-A and functional orexin type 2 receptors in the human adult adrenals: implications for adrenal function and energy homeostasis.

The hypothalamic peptides, orexin-A and orexin-B, have been implicated in the regulation of feeding behavior. In starved rats catabolic activity quickly predominates, reinforced by elevated corticosterone, independent of ACTH, implicating adrenal activity as a metabolic regulator. In view of these findings, we investigated whether orexin and orexin receptors are present in human adult adrenals and might therefore be implicated in hormonal regulation and energy homeostasis outside the central nervous system. RT-PCR, fluorescent in situ hybridization, immunoblotting, and immunostaining analysis confirmed the expression of the orexin type 2 receptor, but not of orexin type 1 receptor, in the adrenal cortex. Immunoblotting analysis also detected the presence of the prepro-orexin and its cleaved product orexin-A. Treatment of adult adrenal membranes with orexin-A increased the labeling of G(s), G(q), and, to a lesser degree, G(i), but not G(o). Stimulation with orexin-A induced cAMP and IP3 production in a dose-dependent manner. The data presented here provide conclusive evidence for the presence of orexin-A and orexin type 2 receptors in human adult adrenal glands. At the moment the functional relevance of this is uncertain. However, it is known that both orexin-A and orexin-B can induce corticosterone production in dispersed rat adrenocortical cells. Our data provide further evidence for a functional link between orexogenic signals and adrenal function. The concept that the peptide acting via these receptors in the adult adrenal is responsible for steroidogenesis and energy balance is attractive.

Expression and coupling characteristics of the CRH and orexin type 2 receptors in human fetal adrenals.

Hormones produced by the fetal adrenal regulate fetal growth, steroidogenic activity, and intrauterine homeostasis, which are essential for the maintenance of pregnancy and the preparation of the fetus for extrauterine life. There is a functional interaction between CRH and the fetal adrenal, as CRH increases dehydroepiandrosterone sulfate production in cultured fetal adrenal cells. Moreover, in a rodent model administration of orexin A induced corticosterone production. To examine this relationship in more detail we measured the expression of the different subtypes of CRH and orexin receptors and their specific coupling to G protein alpha-subunits upon activation with CRH and orexin A, respectively. Using RT-PCR and fluorescent in situ hybridization analysis, we demonstrated the presence of CRH receptors 1alpha and 2alpha, and orexin type 2 receptor mRNA. None of the other CRH receptor variants or orexin type 1 receptor were detected. Immunofluorescent analysis and Western blotting confirmed the protein expression of both receptors, which also bind fluo-CRH and fluo-orexin with high affinity. Immunoblotting analysis confirmed the expression of prepro-orexin and orexin A in fetal adrenals. Using photoaffinity labeling, we determined which G proteins are coupled to the CRH and orexin receptors in fetal adrenals when challenged with CRH or orexin. Treatment of fetal adrenal membranes with CRH (100 nM) increased the labeling of G(o) and, to a lesser extent, G(s), but not G(i) and G(q), whereas treatment with orexin A (100 nM) increased the labeling of G(s) and G(i), but not G(o) and G(q). These findings provide new insights into the components of the signal transduction machinery in human fetal adrenals and demonstrate for the first time the presence of functional orexin receptors outside of the CNS in humans.

Elevated fetal adipsin/acylation-stimulating protein (ASP) in obese pregnancy: novel placental secretion via Hofbauer cells.

CONTEXT AND OBJECTIVE: Obesity in pregnancy is associated with increased risks of obesity in the offspring. We investigated the relationship between obesity in pregnancy and circulating maternal and fetal levels of adipose tissue-derived factors adipsin and acylation stimulating protein (ASP) in lean and obese mothers. DESIGN: Paired peripheral and cord blood samples were taken. Paired fat and placenta tissue were taken for explant culture. Media were assayed for secreted adipsin and ASP. Clinical parameters assayed included fasting insulin, glucose, and adipsin. SETTING: The study was conducted at a university hospital maternity unit. PATIENTS: Patients included 35 lean [body mass index (BMI) 19-25 kg/m(2), mean age 32 years and 39 obese (BMI) > 30 kg/m(2), mean age 32.49 years] pregnant Caucasian women, delivered by cesarean section at term. MAIN OUTCOME MEASURE: Identification of placental macrophages [Hofbauer cells (HBCs)], as a source of adipsin and ASP was determined. RESULTS: HBCs secreted both adipsin and ASP. Cord levels of adipsin (1663.78 ± 52.76 pg/mL) and ASP (354.48 ± 17.17 ng/mL) were significantly elevated in the offspring of obese mothers compared with their lean controls [1354.66 ± 33.87 pg/mL and 302.63 ± 14.98 ng/mL, respectively (P < .05 for both)]. Placentae from obese mothers released significantly more adipsin and ASP than placentae from lean mothers [546.0 ± 44 pg/mL · g vs 284.56 ± 43 pg/mL · g and 5485.75 ± 163.32 ng/mL · g vs 2399.16 ± 181.83 ng/mL · g, respectively (P < .05 for both)]. Circulating fetal adipsin and ASP positively correlated with maternal BMI (r = 0.611, P < .0001, and r = 0.391, P < .05, respectively). Fetal adipsin correlated positively with maternal (r = 0.482, P < .01) and fetal homeostasis model assessment of insulin resistance (r = 0.465, P < .01). CONCLUSIONS: We demonstrate novel secretion of adipsin and ASP by placental HBCs.

Elevated serum levels of visfatin in gestational diabetes: a comparative study across various degrees of glucose tolerance.

AIMS/HYPOTHESIS: Concentrations of visfatin are increased in insulin-resistant conditions, but the relationship between visfatin and insulin and/or insulin resistance indices in pregnancy remains unclear. Insulin resistance in pregnancy is further accentuated in women with gestational diabetes mellitus (GDM). Thus we assessed serum levels of visfatin in pregnant women with varying degrees of glucose tolerance. MATERIALS AND METHODS: Fasting visfatin levels were measured at 28 weeks of gestation in 51 women divided according to their response to a 50-g glucose challenge test (GCT) and a 75-g OGTT: control subjects (n = 20) had normal responses to both a GCT and an OGTT; the intermediate group (IG; n = 15) had a false-positive GCT, but a normal OGTT; the GDM group (n = 16) had abnormal GCTs and OGTTs. RESULTS: There were no age or BMI differences between analysed groups. Across the subgroups there was a progressive increase in glucose and insulin at 120 min of the OGTT (p < 0.01). This was accompanied by an increase in visfatin, from 76.8 +/- 14.1 ng/ml in the control subjects, to 84.0 +/- 14.7 ng/ml in the IG group and 93.1 +/- 12.3 ng/ml in the GDM group (p < 0.01 for GDM vs control subjects). There was a positive correlation between visfatin and fasting insulin (r = 0.38, p = 0.007) and insulin at 120 min of the OGTT (r = 0.39, p = 0.006). CONCLUSIONS/INTERPRETATION: An increase in fasting visfatin, the levels of which correlate with both fasting and post-glucose-load insulin concentrations, accompanies worsening glucose tolerance in the third trimester of pregnancy. However, the significance of these findings, and in particular the role of visfatin in the regulation of insulin sensitivity during pregnancy, remains to be elucidated.

The regulation of adiponectin receptors in human prostate cancer cell lines.

Obesity is a risk factor for prostate cancer, and plasma levels of the adipokine, adiponectin, are low in the former but high in the latter. Adiponectin has been shown to modulate cell proliferation and apoptosis, suggesting that adiponectin and its receptors (Adipo-R1, Adipo-R2) may provide a molecular association between obesity and prostate carcinogenesis. We show for the first time, the protein distribution of Adipo-R1 and Adipo-R2 in LNCaP and PC3 cells, and in human prostate tissue. Using real-time RT-PCR we provide novel data demonstrating the differential regulation of Adipo-R1 and Adipo-R2 mRNA expression by testosterone, 5-alpha dihydrotestosterone, beta-estradiol, tumour necrosis factor-alpha, leptin, and adiponectin in LNCaP and PC3 cells. Our findings suggest that adiponectin and its receptors may contribute to the molecular association between obesity and prostate cancer through a complex interaction with other hormones and cytokines that also play important roles in the pathophysiology of obesity and prostate cancer.