Search

ObjectivesJuvenile idiopathic arthritis (JIA) is one of the most prevalent rheumatic disorders in children and is classified as an autoimmune disease (AID). While a robust genetic contribution to JIA etiology has been established, the exact pathogenesis remains unclear. We conducted a comprehensive integrative analysis to gain new insights into the etiology of JIA.MethodsTo prioritize biologically interpretable susceptibility genes and proteins for JIA, we conducted transcriptome-wide and proteome-wide association studies (TWAS/PWAS). Then, to understand genetic architecture JIA, we systematically analyzed single nucleotide polymorphism (SNP)-based heritability, a signature of natural selection, and polygenicity. Finally, we performed HLA typing using multi-ancestry RNA sequencing data and analyzed the T cell receptor (TCR) repertoire at a single-cell level to investigate the associations between immunity and JIA risk.ResultsWe have identified 19 TWAS genes and two PWAS proteins that are associated with JIA risks. Furthermore, we observe that the heritability and cell type enrichment analysis of JIA are enriched in T lymphocytes and HLA regions, and that JIA shows higher polygenicity compared to other AIDs. In multi-ancestry HLA typing, B*45:01 is more prevalent in African JIA patients than in European JIA patients, whereas DQA1*01:01, DQA1*03:01, and DRB1*04:01 exhibit a higher frequency in European JIA patients. Using single-cell immune repertoire analysis, we identify clonally expanded T cell subpopulations in JIA patients, includingCXCL13+BHLHE40+THcells which are significantly associated with JIA risks.ConclusionsOur findings shed new light on the pathogenesis of JIA and provide a strong foundation for future mechanistic studies aimed at uncovering the molecular drivers of JIA

The plasma atherogenic index (AIP) has been suggested as a useful independent predictor of cardiovascular diseases (CVDs) in high CV risk patients. We investigated the association between AIP and arterial stiffness measured by brachial–ankle pulse wave velocity (baPWV) in healthy adults. A total of 3468 healthy subjects without any metabolic or CV diseases were enrolled. Anthropometric and CV risk factors were measured. The AIP was defined as the base 10 logarithm of the ratio of the concentration of triglycerides to high-density lipoprotein-cholesterol. Subjects were classified into AIP quartiles. There were gradual deteriorations in metabolic parameters and increase in baPWV across the increasing AIP quartiles. In a fully adjusted analysis, compared with Q1 (lowest quartile) group, the odds ratio (95% confidence interval) for increased baPWV was higher in Q2 1.51, Q3 1.64, and Q4 (highest quartile) 2.77 among men, and Q2 1.09, Q3 1.55, and Q4 1.83 among women (all P trend

Background The gender disparity in the thyroid cancer incidence rate, which is 3-folds higher in women than in men, has been hypothesized to be related to estrogen and estrogens receptors (ERs). Recent evidence suggests that nuclear receptor-interacting protein 1 (NRIP1) is known as a coregulator of ERs and a direct target of microRNA-346 (miR-346), which was reported as a biomarker for follicular thyroid carcinoma (FTC). In this study, we investigated the roles of miR-346 on behavioral traits and estrogen-associated pathogenesis of FTCs. Methods Two Human follicular thyroid carcinomas (FTC-133 and RO82-W-1) were used. To examine the effects of miR-346 and estrogen on behavioral traits and estrogen-associated pathogenesis of FTCs, FTC-133 and RO82-W-1 were transfected with the inhibitor targeting human miR-346 or the non-specific miR (-Control), then were treated with 100nM or 200nM of estradiol-17 β (E2). Cell migration and invasion assays were performed; gene and protein levels of NRIP1, ERα, and ERβ were examined by qPCR and western blot, respectively. In addition, cell cycle-regulating genes, epithelial biomarkers, mesenchymal biomarkers were also examined. Results E2 decreased the number of invaded and migrated cells regardless of miR-346-downregulation in both FTCs. Downregulation of miR-346 itself also had protective effects on invasion and migration of both FTCs, and it augmented the inhibitory effects of E2. E2 decreased both gene and protein levels of NRIP1 in FTC-133 while miR-346 downregulation did in RO82-W-1. E2 and miR-346 downregulation decreased the gene and protein expressions of ERα while it increased ERβ, accordingly, decreasing the ratio of ERα to ERβ in both FTCs. E2 significantly decreased cellular proliferation in miR-346 downregulated FTCs. These support that miR-346 has significant roles in estrogen-associated pathogenesis of FTCs by regulating NRIP1 and the interaction of ERα and ERβ. Downregulation of miR-346 increased gene expressions of occluding and cloudin-1 (CLDN1) while decreasing vimentin in FTC-133, it significantly increased gene expressions of CLDN1 in RO82-W-1. These suggest miR-346 in involved in maintaining integrity of FTCs. Conclusion Inhibition of miR-346 in FTCs have protective effects on metastasis, thereby, miR-346 is suggested as a therapeutic target for FTC.

Hyperglycemia is among the main risk factors for severe COVID-19. We evaluated the association of glycated albumin (GA) and GA/HbA1c ratio with progression of COVID-19 from mild to severe disease in patients with type 2 diabetes mellitus (T2DM). Our retrospective study included 129 patients aged over 18 years with COVID-19 and T2DM who did not have any need of oxygen supplement. Of these, 59 patients whose COVID-19 was aggravated and required oxygen supplementation eventually were classified as having severe disease. Clinical and laboratory data were compared between mild and severe cases. The median of GA (18.4% vs. 20.95%, p = 0.0013) and GA/HbA1c (2.55 vs. 2.68, p = 0.0145) were higher in severe disease than in mild disease and positively correlated with C-reactive protein (Kendal Tau coefficient 0.200 and 0.126, respectively; all p < 0.05). Multiple logistic regression analysis showed that GA (odds ratio (OR), 1.151; 95% confidence interval (CI), 1.024–1.294) and GA/HbA1c (OR, 8.330; 95% CI, 1.786–38.842) increased the risk of severe disease. Patients with GA 20% or higher were 4.03 times more likely to progress from mild to severe disease. GA and GA/HbA1c ratio predicted progression of COVID-19 from mild to severe disease in patients with T2DM.

Background. Many Type 2 diabetes (T2DM) patients in Korea take Korean Red Ginseng (KRG) for various reasons. In this study, we investigated the effects of KRG administration on diabetic peripheral neuropathy in T2DM patients. Methods. This study was a randomized, double-blind, placebo-controlled trial. Participants were randomly allocated to either the placebo or KRG group and took corresponding tablets for 24 weeks. The primary outcomes were changes in current perception threshold (CPT) at week 24. Secondary outcomes were altered fasting plasma glucose, HbA1c, and various metabolic and inflammatory markers at week 24. Results. Sixty-one patients completed the study. The CPT of the lower extremities at various frequencies exhibited significant improvements at week 24 in the KRG group. Other metabolic parameters were not altered after 24 weeks in both groups. In the subgroup analysis, CPT levels were improved in those with a longer diabetes duration or who already had neuropathy at the beginning of the study, and insulin resistance was improved in patients with a shorter diabetes duration. Conclusion. Twenty-four week administration of KRG in T2DM patients resulted in a significant improvement in neuropathy, especially in those with a longer diabetes duration. A further, larger population study with a longer follow-up period is warranted to verify the effects of KRG on diabetic neuropathy.

Several experimental studies have suggested beneficial effects ofNinety patients diagnosed with type 2 diabetes (T2DM) for more than 6 months were enrolled. Subjects were randomly divided into placebo (Eighty-four patients completed the study. There were no significant differences in fasting, postprandial glucose, HbA1c, or lipid parameters. HOMA-IR and QUICKI indices were improved at week 12 in theTwelve-week administration of

BACKGROUND/AIMS The importance of α-cell dysfunction in the pathogenesis of type 2 diabetes has re-emerged recently. However, data on whether relative glucagon excess is present in clinical settings are scarce. We aimed to investigate associations between glucagon-to-insulin ratio and various metabolic parameters. METHODS A total of 451 patients with type 2 diabetes naive to insulin treatment were recruited. Using glucagon-to-insulin ratio, we divided subjects into quartiles according to both fasting and postprandial glucagon-to-insulin ratios. RESULTS The mean age of the subjects was 58 years, with a mean body mass index of 25 kg/m2 . The patients in the highest quartile of glucagon-to-insulin ratio had higher glycated hemoglobin (HbA1c) levels. HbA1c levels were positively correlated with both fasting and postprandial glucagon-to-insulin ratios. Subjects in the highest quartile of postprandial glucagon-to-insulin ratio were more likely to exhibit uncontrolled hyperglycemia, even after adjusting for confounding factors (odds ratio, 2.730; 95% confidence interval, 1.236 to 6.028; p for trend < 0.01). CONCLUSION Hyperglucagonemia relative to insulin could contribute to uncontrolled hyperglycemia in type 2 diabetes patients.

Ethnopharmacological relevance Korean red ginseng (KRG) has been traditionally used to treat diabetes. Ginsenosides are considered as the major bioactive components mediating anti-diabetic effects of KRG. However, considering that ginsenosides account for only about 3–4% of ginsengs, other fractions of KRG may also carry potential anti-diabetic effects. There is no study reporting the differentiated effects of ginsenosides (Spn) and non-saponin fractions (NSpn) of KRG on glycemic control. Aim of the study We investigated the effects of KRG, Spn, and NSpn on the indications of glycemic control and sought to elucidate physiological factors contributing their effects. Materials and methods Human T2DM mimicking Nagoya-Shibata-Yasuda (NSY/hos) mice were given KRG, Spn, or NSpn admixed in rodent diet at 200 mg/kg/day for 24 weeks. Glycemic and obesity indications, blood lipid profile, systematic and local oxidative stress markers in metabolically important organs, and systematic inflammatory markers were assessed. Molecular assessments associated with glycemic control in liver and skeletal muscle were further performed. Results KRG attenuated deterioration in glucose homeostasis as evidenced by significantly lower fasting blood glucose from 22nd week and AUC during GTT at the end of the experiment compare to control. Spn enhanced insulin secretion in response to glucose stimulation and reduced protein level of glycogen phosphorylase in liver. On the other hand, NSpn ameliorated oxidative stress and inflammation. Some beneficial effects of Spn and NSpn were reflected in KRG treated mice. KRG also attenuated the accumulation of malondialdehyde in skeletal muscle and, accordingly, enhanced insulin responsiveness compare to control. Conclusion Anti-diabetic properties of KRG are not solely determined by the contents of ginsenosides but the harmonic functions of its different fractions.

Islets are highly vascularized for prompt insulin secretion. Although angiopoietin-1 (Ang1) is a well-known angiogenic factor, its role in glucose homeostasis remains largely unknown. The objective of this study was to investigate whether and how Ang1 contributes to glucose homeostasis in response to metabolic challenge. We used inducible systemic Ang1 knockout (Ang1sys−/−) and β-cell–specific Ang1 knockout (Ang1β-cell−/−) mice fed a high-fat diet for 24 weeks. Although the degree of insulin sensitivity did not differ between Ang1sys−/− and Ang1sys+/+ mice, serum insulin levels were lower in Ang1sys−/− mice, resulting in significant glucose intolerance. Similar results were observed in Ang1β-cell−/− mice, suggesting a critical role of β-cell–derived Ang1 in glucose homeostasis. There were no differences in β-cell area or vasculature density, but glucose-stimulated insulin secretion was significantly decreased, and PDX-1 expression and GLUT2 localization were altered in Ang1β-cell−/− compared with Ang1β-cell+/+ mice. These effects were associated with less pericyte coverage, disorganized endothelial cell ultrastructure, and enhanced infiltration of inflammatory cells and upregulation of adhesion molecules in the islets of Ang1β-cell−/− mice. In conclusion, β-cell–derived Ang1 regulates insulin secretion and glucose homeostasis by stabilizing the blood vessels in the islet and may be a novel therapeutic target for diabetes treatment in the future.

Aims/Introduction Natural killer (NK) cells are cytotoxic lymphocytes critical to human immunity. Previous studies showed correlations between NK cell function and blood glucose concentrations. The purpose of the present study was to assess the NK cell activity and various metabolic parameters in people with type 2 diabetes, prediabetes and normal glucose tolerance. Materials and Methods A total of 49 participants were enrolled in the study. Anthropometric and biochemical parameters including age, sex, body mass index, smoking status, blood pressure, fasting plasma glucose, C‐peptide, insulin, glycated hemoglobin, total cholesterol, triglyceride, high‐density lipoprotein cholesterol and low‐density lipoprotein cholesterol were assessed. The 75 g oral glucose tolerance test was carried out for 2‐h postload glucose level. Homeostatic model assessment was calculated for insulin resistance and β‐cell function. NK cell activity was measured by detecting the circulating interferon‐gamma level secreted from NK cells. Results NK cell activity was lower in patients with type 2 diabetes (768.01 ± 650.35) compared with those with prediabetes (2,396.08 ± 653.76, P

This study investigated the endurance exercise-induced changes in lesser known adipokines (visfatin, chemerin, apelin, semaphorin 3 C) related to obesity and metabolism, and their correlations with the changes in the parameters of obesity and glucose homeostasis. Forty metabolically healthy obese young males were randomly assigned to control group (C, n = 12) or exercise group (Ex, n = 28). The subjects in Ex participated in a 8-week supervised endurance exercise training program, comprised of four sessions of treadmill running at 65–70% of VO2max per week. Serum levels of visfatin, chemerin, apelin, and semaphorin 3 C were significantly decreased in Ex. At baseline, apelin and semaphorin 3 C appeared to be correlated with obesity measures, including body mass index, % total fat and trunk fat, and waist circumference. Exercise-induced changes in these obesity measures significantly correlated with the changes in chemerin and semaphorin 3 C. Basal chemerin, apelin and semaphorin 3 C correlated with glucose homeostasis parameters, including fasting plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance and β-cell function, and quantitative insulin-sensitivity check index to different extents. Furthermore, the changes in apelin and semaphorin 3 C well predicted the improvements in glycemic parameters. We suggest that semaphorin 3 C is a novel adipokine involved in pathophysiology of obesity and metabolism, and that it is a biomarker representing an exercise-induced improvement in metabolically healthy obese young males.

Cluster of differentiation 93 (CD93) is a glycoprotein expressed in activated endothelial cells. The extracellular portion of CD93 can be secreted as a soluble form (sCD93) under inflammatory conditions. As diabetic nephropathy (DN) is a well-known inflammatory disease, we hypothesized that sCD93 would be a new biomarker for DN. We prospectively enrolled 97 patients with type 2 diabetes and evaluated the association between serum sCD93 and DN prevalence. The association between CD93 and development of DN was investigated using human umbilical cord endothelial cells (HUVECs) in vitro and diabetic db/db mice in vivo. Subjects with higher sCD93 levels had a lower estimated glomerular filtration rate (eGFR). The sCD93 level was an independent determinant of both the albumin-to-creatinine ratio (ACR) and the eGFR. The risk of prevalent DN was higher in the high sCD93 group (adjusted odds ratio 7.212, 95% confidence interval 1.244&ndash, 41.796, p = 0.028). In vitro, CD93 was highly expressed in HUVECs and both CD93 expression and secretion were upregulated after lipopolysaccharides (LPS) stimulation. In vivo, peritoneal and urine sCD93 levels and the renal glomerular expression of CD93 were significantly higher in the db/db mice than in the control db/m+ mice. These results suggest the potential of sCD93 as a candidate biomarker associated with DN.

Type 2 diabetes is the fastest growing metabolic disease in the world. Recently, muscle is considered an endocrine organ which secretes various peptides that play an important role in insulin resistance and metabolic syndrome. We assessed 4 different myokines, irisin, interleukin-13 (IL-13), follistatin-related protein-1 (FSTL-1), and fractalkine, in normal, prediabetes, and diabetes patients. A total of 126 participants who visited Gangnam Severance Hospital were enrolled and divided into normal, prediabetes, and diabetes groups based on oral glucose tolerance test and hemoglobin a1c. A cross-sectional study was conducted to measure and compare serum levels of irisin, IL-13, FSTL-1, and fractalkine among the groups. Irisin level showed a tendency to increase in prediabetes group compared to normal group (P

Purpose Oxidative stress plays an important role in the pathogenesis of chronic metabolic diseases. This study investigated the effect of the antioxidant-rich dietary intervention on oxidative stress, metabolic parameters, and arterial stiffness in elderly Koreans with metabolic syndrome (MetS). Materials and Methods Thirty-one subjects with MetS were enrolled and randomly divided into dietary intervention group and control group. Subjects in the intervention group received three meal boxes prepared with antioxidant-rich ingredients every day for 4 weeks, and subjects in the control group maintained their usual diets. Anthropometric and various biochemical parameters related to oxidative stress, inflammation, and MetS were assessed. Brachial-ankle pulse wave velocity (baPWV) and fat measurement using computed tomography were also conducted before and after 4 weeks. Results There were significant differences in waist circumference, visceral to subcutaneous fat ratio, lipid peroxidation, oxidized low density lipoprotein (oxLDL), systolic and diastolic blood pressure, lipid parameters, advanced glycation end products, and baPWV between before and after the study in the experimental group (all p

This study was performed to determine the effectiveness of the Smart Care service on glucose control based on telemedicine and telemonitoring compared with conventional treatment in patients with type 2 diabetes.This 24-week prospective multi-center randomized controlled trial involved 338 adult patients with type 2 diabetes at four university hospitals in South Korea. The patients were randomly assigned to a control group (group A, n = 113), a telemonitoring group (group B, n = 113), or a telemedicine group (group C, n = 112). Patients in the telemonitoring group visited the outpatient clinic regularly, accompanied by an additional telemonitoring service that included remote glucose monitoring with automated patient decision support by text. Remote glucose monitoring was identical in the telemedicine group, but assessment by outpatient visits was replaced by video conferencing with an endocrinologist.The adjusted net reductions in HbA1c concentration after 24 weeks were similar in the conventional, telemonitoring, and telemedicine groups (-0.66% ± 1.03% vs. -0.66% ± 1.09% vs. -0.81% ± 1.05%; p0.05 for each pairwise comparison). Fasting glucose concentrations were lower in the telemonitoring and telemedicine groups than in the conventional group. Rates of hypoglycemia were lower in the telemedicine group than in the other two groups, and compliance with medication was better in the telemonitoring and telemedicine than in the conventional group. No serious adverse events were associated with telemedicine.Telehealthcare was as effective as conventional care at improving glycemia in patients with type 2 diabetes without serious adverse effects.

Over the past three decades, human pancreatic islet isolation and transplantation techniques have developed as a routine clinical procedure for selected patients with type 1 diabetes mellitus. However, due to the donor shortage and required chronic systemic immunosuppression, the widespread application of islet transplantation is limited. To overcome these limitations, providing a physical barrier to transplanted islet cells with encapsulating biomaterial has emerged as a promising approach to enhance engraftment and promote islet survival post-transplantation. Alginate has been considered to be a reliable biomaterial, as it enhances islet survival and does not hamper hormone secretion. Alginate-catechol (Al-CA) hydrogel was reported to provide high mechanical strength and chemical stability without deformation over a wide range of pH values. In this study, we, demonstrated, for the first time in the literature, that encapsulation of murine pancreatic islet cells with Al-CA hydrogel does not induce cytotoxicity ex vivo for an extended period; however, it does markedly abate glucose-stimulated insulin secretion. Catechol should not be considered as a constituent for alginate gelation for encapsulating islet cells in the application of islet transplantation.

Background Diabetes mellitus (DM) is one of the most common diseases worldwide. Uncontrolled and prolonged hyperglycemia can cause diabetic complications, which reduce the quality of life of patients. Diabetic complications are common in DM patients. Because it is impossible to completely recover from diabetic complications, it is important for early detection. In this study, we suggest a novel method of determining blood flow characteristics based on fluorescence image analysis with indocyanine green and report that diabetic complications have unique blood flow characteristics. Methods We analyzed time-series fluorescence images obtained from controls, DM patients, and DM patients with complications. The images were segmented into the digits and the dorsum of the feet and hands, and each part has been considered as arterial and capillary flow. We compared the blood flow parameters in each region among the three groups. Results The DM patients with complications showed similar blood flow parameters to the controls, except the area under the curve and the maximum intensity, which indicate the blood flow volume. These parameters were significantly decreased in DM patients with complications. Although some blood flow parameters in the feet of DM patients with complications were close to normal blood flow, the vascular response of the macrovessels and microvessels to stimulation of the hands was significantly reduced, which indicates less reactivity in DM patients with complications. Conclusions Our results suggest that DM patients, and DM patients with complications, have unique peripheral blood flow characteristics.

Background and aims Coffee is known to have a beneficial effect on various liver diseases. The aim of this retrospective longitudinal study was to investigate an association between the amount of coffee consumption and the incidence of fatty liver disease in Korean adults. Methods and results Data from a total of 91,436 male and female subjects with the mean follow-up period of 2.8 years were analyzed. The incidence of fatty liver was not associated with the amount of coffee consumption at baseline, but it was associated with the change in the amount of coffee consumption at the follow-up period. Multiple linear regression analyses showed that hazard ratios for incidence of fatty liver disease were significantly low in “increase” group comparing with “no change” group in fully adjusted model. When a subgroup analysis by gender was conducted, similar significant results were observed in male subjects, but not in females. Conclusions The increment in the amount of coffee consumption is associated with the lower incidence of fatty liver in Korean men and suggests that increasing the coffee consumption may have a protective effect on fatty liver.

Many studies have demonstrated that an alteration in hemorheological properties is closely correlated with diabetic microcirculatory diseases. However, most of these studies have been limited to animal studies or used a small number of clinical samples, due to a lack of effective point-of-care (POC) devices to measure such properties within clinical environments. Owing to recent developments in microfluidic technology, several hemorheological POC devices have been designed that allow for the possibility of conducting extensive clinical studies using hemorheological measurements. Here, we reviewed recent clinical studies of diabetic kidney disease (DKD) associated with hemorheological parameters. We found that RBC deformability alone did not show a significant difference according to the degree of DKD, whereas critical shear stress (CSS) was found to be closely related to the ratio of albumin to creatinine and glomerular filtration rate. We also reviewed studies that alteration of hemorheological properties are associated with the development of DKD, which showed that CSS could be considered as a potential index to diagnose other diabetic complications as well as DKD.

Background: Baicalin, isolated from Scutellaria baicalensis, has been reported to have anti-inflammatory effect by inhibiting expression of cell adhesion molecules and migration of leukocytes in vascular cells. However, there is a limited evidence on its anti-inflammatory effect in hyperglycemia-associated milieu in other cells. Hyperglycemia and its associated factors are known to induce diabetic nephropathy by exacerbating inflammation, especially, in proximal convoluted tubule. Herein, we investigated whether baicalin exerts anti-inflammatory and anti-fibrosis effects on human renal proximal tubular cells in hyperglycemia induced conditions. Method: HK-2 cell was maintained in normal glycemic (5.78mM glucose) or in hyperglycemic (30mM glucose) condition with or without advanced glycation end-products (AGE) and tumor necrosis factor alpha (TNFα). In each condition, baicalin was treated at 10uM. Cell viability was determined by MTT assay. Gene and protein expression of multiple inflammatory and fibrosis markers including toll-like receptor 2 (TLR2), TLR4, fibronectin, collagen IV α1 (ColIVα1), collagen IV α2 (ColIVα2), transforming growth factor β (TGFβ), intercellular adhesion molecule 1 (ICAM1), and vascular adhesion molecule 1 (VCAM1) were evaluated by PCR and WB, respectively. Results: Baicalin had no effect on cell viability. Baicalin significantly decreased gene expression of ColIVα2 in response to TNFα stimulation in normal glycemic condition (p=0.038). In hyperglycemic condition, baicalin decreased gene expressions of ICAM1 (p=0.049) and VCAM1 (p=0.049) significantly in AGE treated cells; and it significantly decreased gene expressions of TGFβ (p=0.038) and ICAM1 (p=0.017) in TNFα treated cells. Baicalin also decreased protein expression of ICAM1 in response to AGE (p=0.048) and TNFα (p=0.040) stimulation in hyperglycemic condition. Conclusion: Baicalin attenuated fibrosis process by hyperglycemia associated factors in HK-2 cell. Disclosure J. Nam: None. J. Kim: None. K. Park: None. S. Lee: None. J. Nam: None. J. Park: None. S. Park: None. Y. Kim: None. C. Ahn: None.

Objective: FSTL1, an extracellular glycoprotein, is a novel myokine that is secreted by skeletal muscle. However, its functions in metabolism remain unclear, Adipose tissue is one of the important organs for maintaining energy homeostasis. FSTL1 is known to induce inflammatory response and inhibit insulin-mediated Akt signaling pathway, we aimed to investigate whether FSTL1 play metabolic roles in human adipose tissue. We hypothesized that FSTL1 increases lipolysis through its putative receptor DIP2A (Disco interacting protein 2 homolog A). Methods: Human primary adipocytes were treated with recombinant FSTL1 in dose and time dependent manner. To determine its lipolytic activity, pHSL ser563,565,660, perilipin, AMPK, PKA were determined by western blot and the rate of free fatty acid was assessed. Expression of DIP2A was determined by PCR and western blot. DIP2A was knocked-down to examine whether it mediates metabolic effects of FSTL1. Results: FSTL1 did not affect catecholamine-induced lipolysis via PKA. FSTL1, however, increased lipolysis through AMPK activation and, subsequently, HSL ser565 phosphorylation in dose dependent manner. It was found that DIP2A expression did not change during differentiation of human primary adipocyte, suggesting that it is not involved in adipocyte maturation. Conclusion: FSTL1 increased basal lipolysis through AMPK activation. AMPK is well known sensor of the intracellular energy state and serves to regulate various signals. Its activation provides ATP by FA oxidation. Therefore, FSTL1 may play an important in the regulation of energy homeostasis. FSTL1 also has effect through DIP2A. These findings suggest that DIP2A plays important roles in FSTL1 mediated lipolysis. Disclosure C. Ahn: None. A. Choi: None. J. Kim: None. K. Park: None. S. Lee: None. J. Nam: None. S. Park: None. M. Kim: None. Y. Kim: None. J. Nam: None. S. Kang: None. J. Park: None.

Objective: CD93 is a glycoprotein that is known to enhance phagocytosis. The extracellular portion of CD93 can be enzymatically cleaved and secreted to the serum as a soluble form (sCD93). Diabetic nephropathy (DN) is a well-known inflammatory disease that commonly progresses to end stage renal disease (ESRD) in diabetes. Although albuminuria and estimated glomerular filtration rate (eGFR) is currently used for the diagnosis and the prognostication of DN, the prognostic value of the two parameters is modest at best. Here, we hypothesized that sCD93 would be a new biomarker for DN. Methods: We registered 97 human subjects with type 2 diabetes and evaluated the association between serum sCD93 and DN. The underlying mechanism of CD93 regulation was elucidated using human umbilical cord endothelial cell (HUVEC) in vitro and diabetic db/db mice in vivo. Results: The group with higher sCD93 has lower eGFR level and higher prevalence of CKD defined by eGFR. The log(sCD93) was significantly associated with albumin-to-creatinine ratio (ACR) (r=0.229, p=0.028) and the sCD93 level was an independent determinant of ACR and eGFR. The odds ratio of having DN was higher in the high serum sCD93 group even after adjusting for other covariates (adjusted odds ratio 7.283, 95% CI 1.255-42.268, p=0.027). In vitro, CD93 was highly expressed in HUVEC and both CD93 expression and sCD93 secretion was upregulated after LPS stimulation. In db/db mice, sCD93 level was much higher in the peritoneal fluid compared to the db/m mice. The db/db mice showed significantly higher CD93 expression in the renal glomerulus compared to that of the db/m mice suggesting that the elevated sCD93 according to the degree of DN progression might be associated with upregulated expression of CD93 in glomerulus. Conclusion: Based on these human and rodent data, we conclude that sCD93 could be a candidate molecule associated with DN. Disclosure S. Lee: None. H. Park: None. M. Lee: None. A. Choi: None. J. Park: None. C. Ahn: None. S. Lee: None. S. Kang: None. Funding Korean National Research Foundation (2014R1A1A3051221)