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1.
Serum Elabela/Toddler Levels Are Associated with Albuminuria in Patients with Type 2 Diabetes.
Zhang, H, Gong, D, Ni, L, Shi, L, Xu, W, Shi, M, Chen, J, Ai, Y, Zhang, X
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2018;(3):1347-1354
Abstract
BACKGROUND/AIMS: Elabela (ELA) or Toddler is a recently identified hormone that plays a crucial role in embryonic development through the activation of the apelin receptor (APJ). Our previous study indicated that ELA is highly expressed in adult kidney and the ELA receptor signaling pathway is functional in mammalian systems. Whereas nothing is yet known regarding ELA and diabetic kidney disease (DKD). Here, we evaluated the relationship between serum ELA levels and albuminuria in patients with type 2 diabetes (T2D). METHODS An observational study involving 80 patients divided into groups according to their baseline urinary albumin/creatinine ratio (ACR): Group 1 (ACR ≤ 29 mg/g), Group 2 (ACR = 30-299 mg/g), Group 3 (ACR ≥ 300 mg/g with normal serum creatinine), and Group 4 (ACR ≥ 300 mg/g with increased serum creatinine). The demographic, clinical, and biochemical variables including serum ELA were obtained or measured through disease history, physical examination, or laboratory evidence. RESULTS The results showed that the serum ELA levels decreased gradually with the deterioration of DKD from the stages of normal albuminuria, microalbuminuria, macroalbuminuria, to macroalbuminuria and elevated serum creatinine. In addition, ELA had a significantly negative correlation with ACR (r = -0.561, P < 0.001), retinopathy (r = -0.424, P < 0.001), serum creatinine (r = -0.269, P = 0.016), SBP (r = -0.249, P = 0.026), DBP (r = -0.261, P = 0.020) and a positive correlation with eGFR (r = 0.318, P = 0.004). Furthermore, stepwise multiple linear regression analysis showed that ACR, retinopathy, and LDL-C were considered the most relevant variables to ELA, and ELA, retinopathy, eGFR, and age were important predictors for ACR (t = -4.546, P = 0.000). CONCLUSIONS To our knowledge, this is the first study to explore the clinical relationship between ELA levels and CKD. Decreased serum ELA levels might be a significant clinical predictor in patients with DKD or even as a promising agent for treating CKD patients.
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CEP peptide hormones: key players in orchestrating nitrogen-demand signalling, root nodulation, and lateral root development.
Taleski, M, Imin, N, Djordjevic, MA
Journal of experimental botany. 2018;(8):1829-1836
Abstract
Secreted peptide hormones play pivotal roles in plant growth and development. So far, CEPs (C-TERMINALLY ENCODED PEPTIDEs) have been shown to act through CEP receptors (CEPRs) to control nitrogen (N)-demand signalling, nodulation, and lateral root development. Secreted CEP peptides can enter the xylem stream to act as long-distance signals, but evidence also exists for CEPs acting in local circuits. Recently, CEP peptide species varying in sequence, length, and post-translational modifications have been identified. A more comprehensive understanding of CEP biology requires insight into the in planta function of CEP genes, CEP peptide biogenesis, the components of CEP signalling cascades and, finally, how CEP peptide length, amino-acid composition, and post-translational modifications affect biological activity. In this review, we highlight recent studies that have advanced our understanding in these key areas and discuss some future directions.
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ANGPTL8 (betatrophin) role in diabetes and metabolic diseases.
Abu-Farha, M, Abubaker, J, Tuomilehto, J
Diabetes/metabolism research and reviews. 2017;(8)
Abstract
Diabetes is a major disease worldwide that is reaching epidemic levels. Its increased prevalence as well as its association with a high number of complications such as cardiovascular diseases, nephropathy, and retinopathy makes it an important disease for investigation. ANGPTL8 is a recently identified hormone that has been associated with two functionally important processes in the development of type 2 diabetes, insulin resistance as well as lipid metabolism. Initial work has shown that ANGPTL8 was expressed in liver, white adipose, and brown adipose tissues. ANGPTL8 regulates the activity of lipoprotein lipase, which is a key enzyme in lipoprotein lipolysis pathway through its direct interaction with ANGPTL3. It has been also reported that it regulates the replication of β-cells in response to insulin resistance. As a result, many recent studies have focused on the association of ANGPTL8 with diabetes and obesity as well as its association with various metabolic markers in order to better understand its physiological role in glucose homeostasis and lipid metabolism. In this review, we will highlight some of the key clinical findings, mainly from human studies, that investigated the role of ANGPTL8 in metabolic diseases such as diabetes, obesity, and the metabolic syndrome.
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Assessment of circulating betatrophin concentrations in lean glucose-tolerant women with polycystic ovary syndrome.
Erol, O, Özel, MK, Ellidağ, HY, Toptaş, T, Derbent, AU, Yılmaz, N
Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology. 2017;(5):633-638
Abstract
The aims of the current study were to investigate the betatrophin levels in lean glucose-tolerant women with polycystic ovary syndrome (PCOS), and to explore the relationships between these levels and antropometric, hormonal and metabolic parameters. The study population consisted of 50 lean (body mass index [BMI] < 25 kg/m2) women diagnosed with PCOS using the Rotterdam criteria, and 60 age- and BMI-matched healthy controls without any features of clinical or biochemical hyperandrogenism. Before recruitment, glucose tolerance was evaluated in all of the subjects using the 2-h 75 g oral glucose-tolerance test, and only those exhibiting normal glucose tolerance were enrolled. Serum betatrophin levels were significantly higher in women with PCOS (median 322.3; range 44.7-1989.3 ng/L) compared to the controls (median 199.9; range 6.2-1912.9 ng/L; p = .005). In the control group, no significant correlation was evident between betatrophin levels and clinical or biochemical parameters. In the PCOS group, betatrophin levels were positively correlated with prolactin levels (r = .286, p = .046) and negatively correlated with BMI (r = -.283, p = .049), waist/hip ratio (r = -.324, p = .023), and low-density lipoprotein cholesterol levels (r = -.385, p = .006). Impact statement What is already known on this subject: Several studies have suggested that primary alteration in beta-cell function is a pathophysiological feature of PCOS, and insulin resistance is the most significant predictor of beta-cell dysfunction independent of obesity. Betatrophin is a circulating protein that is primarily expressed in the liver in humans. Early experimental investigations demonstrated that overexpression of betatrophin significantly promoted pancreatic beta-cell proliferation, insulin production and improved glucose tolerance. Few studies have investigated the association between PCOS and betatrophin. However, in contrast to our study, the authors included overweight/obese patients and glucose tolerance was not evaluated before recruitment. What the results of this study add: Our results showed that serum betatrophin levels were significantly higher in lean glucose-tolerant PCOS women than in age- and BMI-matched healthy controls. What are the implications of these findings for clinical practice and/or further research: Elevated betatrophin levels in PCOS women, in the absence of obesity and glucose intolerance, may reflect a compensatory mechanism in order to counteract metabolic syndrome-related risk factors.
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Peptide Hormones as Tumor Markers in Clinical Practice.
Sun, Q, Zhao, Z
The Enzymes. 2017;:65-79
Abstract
Peptide hormones represent a major class of hormones that are made from amino acids by specialized endocrine glands. The maturation of bioactive hormones take place in the rough endoplasmic reticulum and Golgi apparatus, where preprohormones are proteolytically cleaved into prohormones, and subsequently into mature peptide hormones. Once the bioactive hormones are released into the circulation, they interact with receptors located on the plasma membrane of target cells, and initiate intracellular signaling pathways to regulate physiological processes including energy metabolism, growth, stress, and reproduction. However, excessive amount of circulating peptide hormones often associates with the presence of tumors. Section 2 discusses 10 peptide hormones as tumor markers and their clinical application in aiding the diagnosis of tumors as well as monitoring the disease process.
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Renal function is independently associated with circulating betatrophin.
Maurer, L, Schwarz, F, Fischer-Rosinsky, A, Schlueter, N, Brachs, S, Möhlig, M, Pfeiffer, A, Mai, K, Spranger, J, Bobbert, T
PloS one. 2017;(3):e0173197
Abstract
OBJECTIVE Betatrophin has been identified as a marker linking liver with beta cell function and lipid metabolism in murine models. Until now, the regulation of circulating betatrophin in humans is not entirely clear. We here analyzed the relation of betatrophin levels to phenotypes of the metabolic syndrome and speculated that renal function might influence circulating betatrophin levels and explain age-dependent changes of betatrophin. SUBJECTS We analyzed blood samples from 535 individuals participating in the Metabolic Syndrome Berlin Potsdam study. RESULTS In a crude analysis we found a positive correlation between betatrophin levels and HbA1c (r = 0.24; p < 0.001), fasting glucose (r = 0.20; p < 0.001) and triglycerides (r = 0.12; p = 0.007). Furthermore betatrophin was positively correlated with age (r = 0.47; p <0.001), systolic blood pressure (r = 0.17; p < 0.001), intima media thickness (r = 0.26; p < 0.001) and negatively correlated with CKD-EPI eGFR (r = -0.33; p < 0.001) as an estimate of renal function. Notably, eGFR remained highly associated with betatrophin after adjustment for age, waist circumference, gender, HbA1c and lipid parameters in a multivariate linear regression model (β = -0.197, p< 0.001). CONCLUSIONS Our data suggest that circulating levels of betatrophin depend on age, gender, waist circumference, total/HDL cholesterol ratio and renal function. Especially the association to eGFR highlights the importance for future studies to address renal function as possible influence on betatrophin regulation and consider eGFR as potential confounder when analyzing the role of betatrophin in humans.
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Circulating ANGPTL8/Betatrophin Concentrations Are Increased After Surgically Induced Weight Loss, but Not After Diet-Induced Weight Loss.
Pascual-Corrales, E, Gómez-Ambrosi, J, Moncada, R, Valentí, V, Catalán, V, Rodríguez, A, Ramírez, B, Silva, C, Gil, MJ, Salvador, J, et al
Obesity surgery. 2016;(8):1881-9
Abstract
BACKGROUND ANGPTL8/betatrophin is a secreted protein reported to be involved in β-cell replication that has recently been shown to be more related to lipid metabolism. Weight loss represents a clinical situation of improvement of glucose homeostasis and overall metabolic control. The aim of the present study was to analyze the impact of weight loss induced by either a conventional dietary treatment or bariatric surgery on ANGPTL8/betatrophin concentrations. METHODS Serum concentrations of ANGPTL8/betatrophin were measured by ELISA in 158 subjects before and 1 year after weight loss induced either by conventional dietary treatment (n = 38) or bariatric surgery (sleeve gastrectomy, n = 20, or Roux-en-Y gastric bypass, n = 100). RESULTS Massive surgery-induced weight loss after SG or RYGB was accompanied by a statistically significant increase in circulating levels of ANGPTL8/betatrophin (28.1 ± 13.9 to 40.3 ± 22.8 ng/mL, P = 0.001 after SG; 24.6 ± 10.9 to 41.7 ± 19.4 ng/mL, P < 0.001 after RYGB), while remaining unchanged 25.6 ± 13.3 to 25.4 ± 10.7 ng/mL (P = 0.891) after diet-induced weight loss. The change in ANGPTL8/betatrophin levels was positively correlated with the change in HDL-C concentrations. CONCLUSIONS Our study showed that serum ANGPTL8/betatrophin concentrations were increased in obese subjects after surgically induced weight loss, but not after weight loss achieved by conventional dietary treatment. The change in ANGPTL8/betatrophin concentrations emerged as a significant predictor of the change in HDL-C levels after weight loss.
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The effect of zinc supplementation on body composition and hormone levels related to adiposity among children: a systematic review.
Gunanti, IR, Al-Mamun, A, Schubert, L, Long, KZ
Public health nutrition. 2016;(16):2924-2939
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Abstract
OBJECTIVE To provide a comprehensive synthesis of the effects of Zn supplementation on childhood body composition and adiposity-related hormone levels. DESIGN Five electronic databases were searched for randomized controlled trials of Zn supplementation studies published before 28 February 2015. No statistical pooling of results was carried out due to diversity in study designs. SETTING Community- or hospital-based, from fourteen developing and developed countries. SUBJECTS Children and adolescents aged 0 to 10 years. RESULTS Seven of the fourteen studies reported an overall or subgroup effect of Zn supplementation on at least one parameter of body composition, when determined by anthropometric measurements (increased mid upper-arm circumference, triceps skinfold, subscapular skinfold and mid upper-arm muscle area, and decreased BMI). Three out of the fourteen studies reported increased mean value of total body water estimated by bio-impedance analysis and increased fat-free mass estimated by dual energy X-ray absorptiometry and by total body water. Zn supplementation was associated with increased fat-free mass among stunted children. One study found supplementation decreased leptin and insulin concentrations. CONCLUSIONS Due to the use of anthropometry when determining body composition, a majority of the studies could not accurately address whether alterations in the fat and/or fat-free mass components of the body were responsible for the observed changes in body composition. The effect of Zn supplementation on body composition is not consistent but may modify fat-free mass among children with pre-existing growth failure.
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Early effects of Roux-en-Y gastric bypass on peptides and hormones involved in the control of energy balance.
Molin Netto, BD, Earthman, CP, Cravo Bettini, S, Grotti Clemente, AP, Landi Masquio, DC, Farias, G, Boritza, K, da Silva, LG, von der Heyde, ME, Dâmaso, AR
European journal of gastroenterology & hepatology. 2016;(9):1050-5
Abstract
INTRODUCTION Body weight varies depending on the prevailing direction of environmental pressures; however, physiological factors also play a significant role in the control of body weight. The aim of the present study was to assess the impact of Roux-en-Y gastric bypass (RYGB) on hormones and peptides involved in the control of energy balance and their possible implications in appetite/satiety. METHODS The sample included 39 individuals with extreme obesity (37 women and two men) who underwent RYGB. Anthropometric and biochemical markers were collected before surgery and 6 months after RYGB. RESULTS The BMI decreased from 44.3±6.4 to 31.7±5.7 kg/m (P<0.001) at the sixth month. Percentage of excess weight lost was 63.2±25.0%. Leptin and glucose levels decreased significantly 6 months after RYGB (P<0.001). Interestingly, a significant correlation was confirmed between the anorexigenic gut hormone peptide YY (PYY) and the central anorexigenic mediator α-melanocyte-stimulating hormone after 6 months of RYGB (r=0.35, P=0.004). In contrast, PYY concentrations were correlated negatively with BMI (r=-0.34, P=0.002). CONCLUSION In the present investigation, it was found that there is a relationship between α-melanocyte-stimulating hormone and PYY concentrations, and it supports the role of the PYY to POMC signal in appetite regulation after RYGB.
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Postprandial effects of consuming a staggered meal on gut peptide and glycemic responses in obese women and men.
Griffith, L, Haddad, EH, Tonstad, S
Obesity research & clinical practice. 2016;(3):264-74
Abstract
Eating slowly by staggering a meal may reduce energy intake. Our aim was to examine the effect of eating a portion of beans 15min before the rest of the meal, on gastrointestinal (GI) peptides, glucose and insulin concentrations and subsequent energy intake in obese adults. This was a randomised crossover design study with 28 obese subjects. Participants consumed a standardised breakfast on test days followed by test meals: (1) control meal containing 86g (0.5 cup) of beans, and (2) staggered meal in which 86g (0.5 cup) of beans were consumed 15min before the rest of the meal. Blood obtained prior to and at 30, 60, and 120min following the meals was analysed for acylated ghrelin, unacylated ghrelin, glucagon-like peptide-1 (GLP-1), peptide YY, oxyntomodulin, glucose and insulin. Feelings of hunger and satiety were assessed using analog visual scales. Energy intake following the test meal was obtained by computer assisted dietary recalls. Mixed model statistical analysis of data showed time effects for unacylated ghrelin, GLP-1, glucose, insulin, hunger and fullness, however, meal effects were not shown for any of the parameters. GLP-1 area under the curve from baseline to 120min (AUC0-120) decreased by 19% (P=0.024) and that of glucose increased by 7% (P=0.046) following the staggered compared to the control bean meal. Energy intake subsequent to the test meals did not differ between treatments. In conclusion, lengthening meal times by staggering eating did not benefit hormonal, metabolic or appetite control in obese individuals.