The stimulatory effect of HI 129, a novel indole derivative, on glucose-induced insulin secretion.

Indole derivatives exhibit a broad spectrum of beneficial effects, encompassing anti-inflammatory, antiviral, antimalarial, anti-diabetic, antioxidant, anti-hepatitis, and antidepressant properties. Here, we describe the potentiation of insulin secretion in pancreatic islets and INS-1 cells through methyl 2-(2-ethoxy-1-hydroxy-2-oxoethyl)-1-(pyrimidine-2-yl)-1H-indole-3-carboxylate (HI 129), a novel indole derivative. Treatment with HI 129 led to notably decreased ADP/ATP ratios in pancreatic islets and INS-1 cells compared to those in the vehicle-treated controls, indicating a shift in cellular ATP production.

S6K1 deficiency in tumor stroma impairs lung metastasis of melanoma in mice.

Accumulating data suggest that ribosomal protein S6 kinase 1 (S6K1), an effector in the mammalian target of rapamycin (mTOR) pathway, plays pleiotropic roles in tumor progression. However, to date, while the tumorigenic function of S6K1 in tumor cells has been well elucidated, its role in the tumor stroma remains poorly understood. We recently showed that S6K1 mediates vascular endothelial growth factor A (VEGF-A) production in macrophages, thereby supporting tumor angiogenesis and growth.

The Novel Inhibitory Effect of YM976 on Adipocyte Differentiation.

The pyrimidine derivative YM976 (4-(3-chlorophenyl)-1,7-diethylpyrido(2,3-)-pyrimidin-2(1)-one) exerts anti-inflammatory and anti-asthmatic effects. Considering that accumulation of lipids in adipose tissue is accompanied by inflammation, we investigated whether YM976 affects adipocyte differentiation. We found that YM976 significantly decreased lipid accumulation without cytotoxicity and reduced the expression levels of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα) as well as their lipogenic regulators including fatty acid synthase (FASN) and fatty acid-binding protein 4 (FABP4) in 3T3-L1 cells induced for differentiation.

Anti-Adipogenic Effects of Salicortin from the Twigs of Weeping Willow () in 3T3-L1 Cells.

(), the "weeping willow," has been used in traditional Korean medicine to treat pain and fever due to its high concentrations of salicylic acid and salicin. The present study investigated bioactive compounds from twigs to discover bioactive natural products. Phytochemical investigation of the ethanol (EtOH) extract of twigs followed by liquid chromatography-mass spectrometry (LC/MS)-based analysis led to the isolation of two salicin derivatives, salicortinol and salicortin, the structures of which were determined by interpretation of their NMR spectra and data from the LC/MS analysis.

Bioactive Phytochemicals from Twigs: Anti-Adipogenic Effect of 2'--Acetylsalicortin in 3T3-L1 Cells.

(Salicaceae) is a willow tree and has been used as a medicinal herb in Korea to treat pain and fever. As a part of an ongoing study to identify bioactive natural products, potential anti-adipogenic compounds were investigated using the ethanol (EtOH) extract of twigs. Phytochemical investigation of the EtOH extracts using liquid chromatography-mass spectrometry (LC/MS) led to the separation of two compounds, oregonin () and 2'--acetylsalicortin ().

Novel anti-adipogenic effect of CF-allylated indole in 3T3-L1 cells.

Indole derivatives from various plants are known to have health benefits because of their anti-cancer, anti-oxidant, anti-inflammatory, and anti-tubercular effects. However, their effects on adipogenesis have not been fully elucidated yet. Herein, we show that a newly synthesized indole derivative, CF-allylated indole, [(E)-1-(pyrimidin- 2-yl)-2-(4,4,4- trifluorobut-2-enyl)-1H-indole], effectively inhibits adipogenesis.

Exosome-Mediated Differentiation of Mouse Embryonic Fibroblasts and Exocrine Cells into β-Like Cells and the Identification of Key miRNAs for Differentiation.

Diabetes is a concerning health malady worldwide. Islet or pancreas transplantation is the only long-term treatment available; however, the scarcity of transplantable tissues hampers this approach. Therefore, new cell sources and differentiation approaches are required.

Loss of S6K1 But Not S6K2 in the Tumor Microenvironment Suppresses Tumor Growth by Attenuating Tumor Angiogenesis.

Two isoforms of the 70-kDa ribosomal protein S6 kinase, S6K1 and S6K2, have been identified and are considered key downstream effectors of the mTOR signaling pathway, which is involved in tumor growth and progression. However, their biological roles in the tumor microenvironment are poorly understood. In this study, utilizing tumor xenograft models in S6k1 and S6k2 mice, we show that loss of S6K1 but not S6K2 in the tumor stroma suppresses tumor growth, accompanied by attenuated tumor angiogenesis.

Carbamazepine Enhances Adipogenesis by Inhibiting Wnt/β-catenin Expression.

Carbamazepine is a drug that is widely used in the treatment of epilepsy and bipolar disorder. The prevalence of obesity in patients treated with carbamazepine has been frequently reported. However, whether carbamazepine affects adipogenesis, one of the critical steps in the development of obesity, remains unclear.

Vacuolar H-ATPase Subunit V0C Regulates Aerobic Glycolysis of Esophageal Cancer Cells via PKM2 Signaling.

The vacuolar H-adenosine triphosphatase (ATPase) subunit V0C (ATP6V0C), a proton-conducting, pore-forming subunit of vacuolar ATPase, maintains pH homeostasis and induces organelle acidification. The intracellular and extracellular pH of cancer cells affects their growth; however, the role of ATP6V0C in highly invasive esophageal cancer cells (ECCs) remains unclear. In this study, we examined the role of ATP6V0C in glucose metabolism in ECCs.

A single extra copy of Down syndrome critical region 1-4 results in impaired hepatic glucose homeostasis.

Objectives: During fasting, hepatic gluconeogenesis is induced to maintain energy homeostasis. Moreover, abnormal dysregulation of hepatic glucose production is commonly observed in type 2 diabetes. However, the signaling components controlling hepatic glucose production to maintain normal glucose levels are not fully understood.

Allicin induces beige-like adipocytes via KLF15 signal cascade.

Under specific conditions, white adipose tissue (WAT) depots are readily converted to a brown-like state, which is associated with weight loss. However, whether diet-derived factors directly induce browning of white adipocytes has yet to be established. Thus, we investigated the effects of allicin, one of the major components of garlic, on brown-like adipocyte formation in inguinal WAT (iWAT), and prevention of obesity and related complications in animal models.

Association between nonalcoholic fatty liver disease and bone mineral density in postmenopausal women.

Objective: Growing evidence suggests that nonalcoholic fatty liver disease (NAFLD) is associated with reduced bone mineral density (BMD). This study examined the association between NAFLD and BMD in postmenopausal Korean women.

Methods: This retrospective cross-sectional study analyzed 3739 postmenopausal women aged 50-59 years who visited a health promotion center for a routine checkup from 2009 to 2014.

Trichostatin A resistance is facilitated by HIF-1α acetylation in HeLa human cervical cancer cells under normoxic conditions.

Trichostatin A (TSA) is an anticancer drug that inhibits histone deacetylases (HDACs). Hypoxia-inducible factor 1 (HIF-1) participates in tumor angiogenesis by upregulating target genes, such as vascular endothelial growth factor (VEGF). In the present study, we investigated whether TSA treatment increases HIF-1α stabilization acetylation under normoxic conditions, which would lead to VEGF upregulation and resistance to anticancer drugs.

Growth differentiation factor 15 predicts advanced fibrosis in biopsy-proven non-alcoholic fatty liver disease.

Background & Aims: We explored whether growth differentiation factor 15 (GDF15) affects the histological severity of non-alcoholic fatty liver disease (NAFLD) independent of insulin resistance.

Methods: In a biopsy-proven NAFLD cohort, we measured serum GDF15 levels using enzyme-linked immunosorbent assays.

Results: Among 190 subjects (mean age, 53 ± 14 years; men, 52.

mTOR controls ChREBP transcriptional activity and pancreatic β cell survival under diabetic stress.

Impaired nutrient sensing and dysregulated glucose homeostasis are common in diabetes. However, how nutrient-sensitive signaling components control glucose homeostasis and β cell survival under diabetic stress is not well understood. Here, we show that mice lacking the core nutrient-sensitive signaling component mammalian target of rapamycin (mTOR) in β cells exhibit reduced β cell mass and smaller islets.

Sinigrin attenuates the progression of atherosclerosis in ApoE mice fed a high-cholesterol diet potentially by inhibiting VCAM-1 expression.

Atherosclerosis is a complex inflammatory disease associated with elevated levels of atherogenic molecules for leukocyte recruitment. Sinigrin (2-propenylglucosinolate) is found mainly in broccoli, brussels sprouts, and black mustard seeds. Recently, sinigrin has received attention for its role in disease prevention and health promotion.

Synovial cell death is regulated by TNF-α-induced expression of B-cell activating factor through an ERK-dependent increase in hypoxia-inducible factor-1α.

B-cell activating factor (BAFF) has a role in the maturation and maintenance of B cells and is associated with rheumatoid arthritis (RA). Here, we investigated whether tumor necrosis factor (TNF)-α-induced BAFF expression controls the survival of fibroblast-like synoviocytes (FLS) and whether their survival can be regulated by TNF-α-mediated upregulation of hypoxia-inducible factor (HIF)-1α using MH7A synovial cells transfected with the SV40 T antigen. More TNF-α-treated cells died compared with the control.

Sinigrin inhibits production of inflammatory mediators by suppressing NF-κB/MAPK pathways or NLRP3 inflammasome activation in macrophages.

Sinigrin (2-propenyl glucosinolate) is found mainly in broccoli, brussels sprouts, and black mustard seeds. Recently, sinigrin has received attention for its role in disease prevention and health. This study investigated the effect of sinigrin on macrophage function, including the activity of Nod-like receptor protein 3 (NLRP3) inflammasome.

Depot-specific differences in angiogenic capacity of adipose tissue in differential susceptibility to diet-induced obesity.

Objective: Adipose tissue (AT) expansion requires AT remodeling, which depends on AT angiogenesis. Modulation of AT angiogenesis could have therapeutic promise for the treatment of obesity. However, it is unclear how the capacity of angiogenesis in each adipose depot is affected by over-nutrition.

Redox-Neutral Rh(III)-Catalyzed Olefination of Carboxamides with Trifluoromethyl Allylic Carbonate.

The rhodium(III)-catalyzed olefination of various carboxamides with α-CF-substituted allylic carbonate is described. This reaction provides direct access to linear CF-allyl frameworks with complete trans-selectivity. In particular, a rhodium catalyst provided Heck-type γ-CF-allylation products via the β-O-elimination of rhodacycle intermediate and subsequent olefin migration process.

Polarized macrophages treated with nonylphenol differently regulate lipopolysaccharide-induced sepsis.

Nonylphenol (NP) as well-known "endocrine disrupter" influences sexual and reproductive development. Here, we investigated the effect of NP on M1-/M2-type macrophages and their role in lipopolysaccharide (LPS)-induced sepsis. Polarized macrophages of M1- and M2-types were obtained by the treatment with LPS and interleukin-4 (IL-4) to bone marrow-derived macrophages (BMDM), respectively.

Interferon-alpha inhibits adipogenesis via regulation of JAK/STAT1 signaling.

Background Information: Adipose tissue regulates energy metabolism by means of adipocyte hypertrophy and/or the differentiation of pre-existing adipocytes. Excessive production of some cytokines in adipose tissue is known to be a negative regulator of adipocyte differentiation, and the resulting impaired adipogenesis contributes to disorders like insulin resistance. IFN-α is a key immunoregulatory cytokine in the development of type 1 diabetes, lipid disorders and insulin resistance; however, its effect on adipogenesis remains unknown.