• Hviid Thorhauge posted an update 3 days, 19 hours ago

    BACKGROUND We describe the association between high density lipoprotein cholesterol (HDL-C) concentration and computed tomography (CT)-measured fat depots. METHODS We examined the cross-sectional associations between HDL-C concentration and intra-abdominal (IAF), abdominal subcutaneous (SCF), and thigh fat (TF) areas in 641 Japanese-American men and women. IAF, SCF, and TF were measured by CT at the level of the umbilicus and mid-thigh. The associations between fat area measurements and HDL-C were examined using multivariate linear regression analysis adjusting for age, sex, diabetes family history, homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index (BMI). Non-linearity was assessed using fractional polynomials. RESULTS Mean±standard deviation of HDL-C concentration and IAF in men and women were 1.30±0.34 mg/dL, 105±55.3 cm², and 1.67±0.43 mg/dL, 74.4±46.6 cm² and differed significantly by gender for both comparisons (P less then 0.001). In univariate analysis, HDL-C concentration was significantly associated with CT-measured fat depots. In multivariate analysis, IAF was significantly and non-linearly associated with HDL-C concentration adjusted for age, sex, BMI, HOMA-IR, SCF, and TF (IAF β=-0.1012, P less then 0.001; IAF2 β=0.0008, P less then 0.001). SCF was also negatively and linearly associated with HDL-C (β=-0.4919, P=0.001). CONCLUSION HDL-C does not linearly decline with increasing IAF in Japanese-Americans. A more complex pattern better fits this association. Copyright © 2019 Korean Diabetes Association.Cyclic adenosine monophosphate (cAMP) signaling is critical for regulating metabolic homeostasis in mammals. In particular, transcriptional regulation by cAMP response element-binding protein (CREB) and its coactivator, CREB-regulated transcription coactivator (CRTC), is essential for controlling the expression of critical enzymes in the metabolic process, leading to more chronic changes in metabolic flux. Among the CRTC isoforms, CRTC2 is predominantly expressed in peripheral tissues and has been shown to be associated with various metabolic pathways in tissue-specific manners. While initial reports showed the physiological role of CRTC2 in regulating gluconeogenesis in the liver, recent studies have further delineated the role of this transcriptional coactivator in the regulation of glucose and lipid metabolism in various tissues, including the liver, pancreatic islets, endocrine tissues of the small intestines, and adipose tissues. In this review, we discuss recent studies that have utilized knockout mouse models to delineate the role of CRTC2 in the regulation of metabolic homeostasis. Copyright © 2020 Korean Diabetes Association.BACKGROUND Notch signaling pathway plays an important role in regulating pancreatic endocrine and exocrine cell fate during pancreas development. Notch signaling is also expressed in adult pancreas. There are few studies on the effect of Notch on adult pancreas. KU-60019 chemical structure Here, we investigated the role of Notch in islet mass and glucose homeostasis in adult pancreas using Notch1 antisense transgenic (NAS). METHODS Western blot analysis was performed for the liver of 8-week-old male NAS mice. We also conducted an intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test in 8-week-old male NAS mice and male C57BL/6 mice (control). Morphologic observation of pancreatic islet and β-cell was conducted in two groups. Insulin secretion capacity in islets was measured by glucose-stimulated insulin secretion (GSIS) and perifusion. RESULTS NAS mice showed higher glucose levels and lower insulin secretion in IPGTT than the control mice. There was no significant difference in insulin resistance. Total islet and β-cell masses were decreased in NAS mice. The number of large islets (≥250 μm) decreased while that of small islets ( less then 250 μm) increased. Reduced insulin secretion was observed in GSIS and perifusion. Neurogenin3, neurogenic differentiation, and MAF bZIP transcription factor A levels increased in NAS mice. CONCLUSION Our study provides that Notch1 inhibition decreased insulin secretion and decreased islet and β-cell masses. It is thought that Notch1 inhibition suppresses islet proliferation and induces differentiation of small islets. In conclusion, Notch signaling pathway may play an important role in β-cell mass determination and diabetes. Copyright © 2020 Korean Diabetes Association.BACKGROUND Low-dose persistent organic pollutants (POPs), especially organochlorine pesticides (OCPs), have emerged as a new risk factor of many chronic diseases. As serum concentrations of POPs in humans are mainly determined by both their release from adipose tissue to circulation and their elimination from circulation, management of these internal pathways may be important in controlling the serum concentrations of POPs. As habitual physical activity can increase the elimination of POPs from circulation, we evaluated whether chronic physical activity is related to low serum POP concentrations. METHODS A cross-sectional study of 1,850 healthy adults (age ≥20 years) without cardio-metabolic diseases who participated in the U.S. NHANES 1999-2004 was conducted. Information on moderate or vigorous leisure-time physical activity was based on questionnaires. Serum concentrations of OCPs and polychlorinated biphenyls were investigated as typical POPs. RESULTS Serum concentrations of OCPs among physically active subjects were significantly lower than those among physically inactive subjects (312.8 ng/g lipid vs. 538.0 ng/g lipid, P less then 0.001). This difference was maintained after adjustment for potential confounders. When analyses were restricted to physically active subjects, there were small decreases in the serum concentrations of OCPs with increasing duration of physical activity, showing a curvilinear relationship over the whole POP range (Pquadratic less then 0.001). In analyses stratified by age, sex, body mass index, and smoking status, a strong inverse association was similarly observed among all subgroups. CONCLUSION Physical activity may assist in decreasing serum concentrations of lipophilic chemical mixtures such as OCPs. Copyright © 2020 Korean Diabetes Association.