Metformin is associated with increased insulin sensitivity, whereas oral contraceptive pills (OCP) could increase the risk for type 2 diabetes (T2D) in women with polycystic ovary syndrome (PCOS). Certain microRNAs (miRNAs) might serve as biomarkers for the risk of T2D. The aim of this study was to investigate changes in circulating miRNA levels during treatment with metformin and OCP in women with PCOS. Sixty-five women with PCOS according to Rotterdam criteria were randomized to metformin (2g/d), metformin+OCP (150 mg desogestrel + 30 µg ethinylestradiol) or OCP alone for 12 months. Serum miRNA analysis was performed with individual RT-qPCR or Taqman Low Density Array cards of 22 selected miRNAs previously related to PCOS, glucose and/or lipid metabolism. MiR-122 and miR-29a levels were decreased after treatment with metformin compared with metformin+OCP and OCP group: miR-122: log2 difference -0.7 (p= 0.01) and -0.7 (p= 0.02), miR-29a: log2 difference -0.5 (p= 0.01) and -0.4 (p= 0.04), while miR-223 levels were decreased in the metformin+OCP group after treatment: log2 difference -0.5 (p=0.02). During the treatment period, a significant weight loss was observed in the metformin group compared with the OCP group. In the OCP group, miRNA levels were unchanged during the treatment period. Levels of circulating miRNAs associated with lipid and glucose metabolism decreased during metformin treatment. Changes in miRNA levels in the metformin group could be explained by the simultaneous weight loss in the same group. These results support the notion that metformin treatment alone may be superior for metabolic health compared with OCP.
Pernille Bækgaard Udesen, Dorte Glintborg, Anja Elaine Sørensen, Rikke Svendsen, Nanna Louise Skov Nielsen, Marie Louise Muff Wissing, Marianne Skovsager Andersen, Anne Lis Mikkelsen Englund, and Louise Torp Dalgaard
Caishun Zhang, Junhua Yuan, Qian Lin, Manwen Li, Liuxin Wang, Rui Wang, Xi Chen, Zheng-Yao Jiang, Kun Zhu, Xiaoli Chang, Bin Wang, and Jing Dong
Ghrelin plays a pivotal role in the regulation of food intake, body weight and energy metabolism. However, these effects of ghrelin in the lateral parabrachial nucleus (LPBN) are unexplored. C57BL/6J mice and GHSR-/- mice were implanted with cannula above the right LPBN and ghrelin was microinjected via the cannula to investigate effect of ghrelin in the LPBN. In vivo electrophysiological technique was used to record LPBN glucose sensitive neurons to explore potential underlying mechanisms. Microinjection of ghrelin in LPBN significantly increased food intake in the first 3 hours, while such effect was blocked by [D-Lys3]-GHRP-6 and abolished in GHSR-/- mice. LPBN ghrelin microinjection also significantly increased the firing rate of glucose-excited (GE) neurons and decreased the firing rate of glucose-inhibited (GI) neurons. Additionally, LPBN ghrelin microinjection also significantly increased c-fos expression. Chronic ghrelin administration in the LPBN resulted in significantly increased body weight gain. Meanwhile, no significant changes were observed in both mRNA and protein expression levels of UCP-1 in BAT. These results demonstrated that microinjection of ghrelin in LPBN could increase food intake through the interaction with growth hormone secretagogue receptor (GHSR) in C57BL/6J mice, and its chronic administration could also increase body weight gain. These effects might be associated with altered firing rate in the GS and GI neurons.
Jeyanthini Risikesan, Birgitte Nellemann, Britt Christensen, Jens Otto Lunde Jørgensen, and Søren Nielsen
Studies indicate that erythropoietin (EPO) has effect on lipid and energy metabolism; however, the impact of EPO on lipid oxidation in vivo has not been well documented. Here, we evaluate whether long-term erythropoiesis-stimulating agent (ESA) treatment affects the oxidation of plasma very low-density lipoprotein triglycerides (VLDL–TG) fatty acids (FA) , plasma free fatty acids (FFA) and non-plasma (residual) FA in healthy, young, sedentary men. Infusion of [1-14C]VLDL-TG and [9,10-3H]palmitate was used in combination with indirect calorimetry to assess resting lipid fuel utilization and kinetics, and resting energy expenditure (REE) before and after 10 weeks of ESA exposure compared with placebo. REE increased significantly during ESA compared with placebo (P=0.023, RM-ANOVA). Oxidation rates of VLDL-TG FA, FFA, and residual FA remained unchanged during ESA compared with placebo. The relative contribution of the lipid stores was greatest for FFA (47.1%) and the total lipid oxidation rate and was not significantly different between ESA and placebo treated subjects. We conclude that long-term ESA treatment of healthy young men increases REE but does not alter the oxidation rates of plasma and non-plasma FA sources.
Anna Eremkina, Julia Krupinova, Ekaterina Dobreva, Anna Gorbacheva, Ekaterina Bibik, Margarita Samsonova, Alina Ajnetdinova, and Natalya Mokrysheva
Hypercalcemic crisis is a severe but rare complication of primary hyperparathyroidism (PHPT), and data on denosumab treatment of patients with this disease is still very limited. The aim of this paper is to investigate the hypocalcemic effect of denosumab in PHPT patients with severe hypercalcemia when surgery should be delayed or is impossible for some reasons. We performed a retrospective study of 10 patients. The analysis included the use of biochemical markers of calcium-phosphorus metabolism, which were followed after the administration of 60 mg of denosumab. The trend to calcium reduction was already determined on the 3rd day after denosumab administration. In most cases the decrease in serum calcium level to the range of 2.8 mmol/L on average or lower was observed on the 7th day (p=0.002). In addition to a significant increase in calcium levels we confirmed a significant increase in the estimated glomerular filtration rate on 7th day (p=0.012). After that, 7 patients underwent successful parathyroidectomy and achieved eucalcemia or hypocalcemia, one patient developed the recurrence of parathyroid cancer after initial surgery, while two patients with severe cardiovascular pathology refused surgery. Our study shows that denosumab is a useful tool in PHPT-associated hypercalcemia before surgery or if surgery is contraindicated.
Ju-shuang Li, Tao Wang, Jing-jing Zuo, Cheng-nan Guo, Fang Peng, Shu-zheng Zhao, Hui-hui Li, Xiang-qing Hou, Yuan Lan, Ya-ping Wei, Chao Zheng, and Guang-yun Mao
Diabetic retinopathy (DR), the most common microvascular complication of diabetes and leading cause of visual impairment in adults worldwide, is suggested to be linked to abnormal lipid metabolism. The present study aims to comprehensively investigate the relationship between n-6 polyunsaturated fatty acids (PUFAs) and DR. This was a propensity score matching based case-control study, including 69 pairs of DR patients and type 2 diabetic patients without DR with mean age of 56.7 ± 9.2 years. Five n-6 PUFAs were determined by UPLC-ESI-MS / MS system. Principle component regression (PCR) and multiple conditional logistic regression models were used to investigate the association of DR risk with n-6 PUFAs depending on independent training and testing sets, respectively. According to locally weighted regression model, we observed obvious negative correlation between levels of five n-6 PUFAs (linoleic acid, γ-linolenic acid, eicosadienoic acid, dihomo-γ-linolenic acid and arachidonic acid) and DR. Based on multiple PCR model, we also observed significant negative association between the five n-6 PUFAs and DR with adjusted OR (95% CI) as 0.62 (0.43,0.87). When being evaluated depending on the testing set, the association was still existed, and PCR model had excellent classification performance, in which area under the curve (AUC) was 0.88 (95%CI: 0.78, 0.99). In addition, the model also had valid calibration with a non-significant Hosmer-Lemeshow Chi-square of 9.44 (P = 0.307) in the testing set. n-6 PUFAs were inversely associated with the presence of DR, and the principle component could be potential indicator in distinguishing DR from other T2D patients.
Taísa A R Vicente, Ívina E S Rocha, Roberto Salvatori, Carla R P Oliveira, Rossana M C Pereira, Anita H O Souza, Viviane C Campos, Elenilde G Santos, Rachel D C Araújo Diniz, Eugênia H O Valença, Carlos C Epitácio-Pereira, Mario C P Oliveira, Andrea Mari, and Manuel H Aguiar-Oliveira
effect is likely to be completely absent). It is conceivable that the lack of a GHRH effect per se may have additional consequences on glucose metabolism independent of GHD. It is also possible that the self-reporting approach may have underestimated
M Ahmid, C G Perry, S F Ahmed, and M G Shaikh
, although the evidence base underlying this recommendation is limited ( 8 ). Figure 1 GH–IGF1 axis and actions in bone, muscle and body metabolism. GH secretion is regulated by three peptides: GH-releasing hormone (GHRH), ghrelin-stimulating GH
Esben Thyssen Vestergaard, Morten B Krag, Morten M Poulsen, Steen B Pedersen, Niels Moller, Jens Otto Lunde Jorgensen, and Niels Jessen
the period from t =120 to t =300 min as the clamp period. Serum RBP4 levels were measured twice each study day: at baseline ( t =−60 min) and during the clamp at t =300 min. Data on glucose metabolism, insulin sensitivity, and energy expenditure
Adriano N Cury, Verônica T Meira, Osmar Monte, Marília Marone, Nilza M Scalissi, Cristiane Kochi, Luís E P Calliari, and Carlos A Longui
Pediatric Endocrinology and Metabolism 2001 14 229 – 243 . ( doi:10.1515/JPEM.2001.14.3.229 ). 2 Kaguelidou F Carel JC Leger J . Graves' disease in childhood: advances in management with antithyroid drug therapy
E Vignali, F Cetani, S Chiavistelli, A Meola, F Saponaro, R Centoni, L Cianferotti, and C Marcocci
levels (e.g. Paget's disease) should be excluded. Finally, the use of medications which might affect PTH levels or calcium metabolism (estrogens, thiazide diuretics, lithium, bisphosphonates, denosumab and anticonvulsants) should also be ruled out (4