Regulation and Roles of Urocortins in the Vascular System

Urocortins (Ucns) are members of the corticotropin-releasing factor (CRF) family of peptides. Ucns would have potent effects on the cardiovascular system via the CRF receptor type 2 (CRF2 receptor). Regulation and roles of each Ucn have been determined in the vascular system. Ucns have more potent vasodilatory effects than CRF. Human umbilical vein endothelial cells (HUVECs) express Ucns1-3 mRNAs, and the receptor, CRF2a receptor mRNA. Ucns1-3 mRNA levels are differentially regulated in HUVECs. Differential regulation of Ucns may suggest differential roles of those in HUVECs. Ucn1 and Ucn2 have strong effects on interleukin (IL)-6 gene expression and secretion in rat aortic smooth muscle A7r5 cells. The increase that we observed in IL-6 levels following Ucn treatment of A7r5 cells suggests that smooth muscle cells may be a source of IL-6 secretion under physiological stress conditions. Ucns are important and unique modulators of vascular smooth muscle cells and act directly or indirectly as autocrine and paracrine factors in the vascular system

Possible Insulinotropic Action of Apolipoprotein A–I Through the ABCA1/Cdc42/cAMP/PKA Pathway in MIN6 Cells

Aims/Introduction: We studied the mechanisms for the possible insulinotropic action of apolipoprotein (Apo) A–I in mouse insulinoma (MIN6) cells.Materials and Methods: The effects of ApoA-I on cAMP production and glucose-stimulated insulin secretion (GSIS), and the dose dependency (ApoA-I at 5, 10, 25, and 50 μg/ml) were determined using MIN6 cells. The effects of the small-interference ribonucleic acid (siRNA) of ATP-binding cassette transporter A1(ABCA1) and Cell division control protein 42 homolog (Cdc42) on the insulinotropic action of ApoA-I was studied, as well as mRNA and protein levels of ABCA1 and Cdc42. Then, the influence of cAMP inhibitor SQ22536, and the cAMP-dependent protein kinase inhibitor Rp-cAMPS on ApoA-I action were studied.Results: Addition of ApoA-I produced cAMP and increased insulin secretion, dose-dependently in high glucose concentration (25 mmmol/l). and ABCA1 protein and Cdc42 mRNA and protein were also enhanced. Specific ABCA1 and Cdc42 siRNA significantly decreased the effects of ApoA-I on insulin secretion compared with negative controls. Manifestations of ABCA1 and Cdc42 mRNA and protein were less than that of the negative control group. Both cAMP inhibiror (SQ22536) and protein kinases inhibitor (Rp-cAMPS) strongly inhibited the effects of ApoA-I on insulin secretion.Conclusions: We demonstrated that ApoA-I enhances glucose-stimulated insulin release in high glucose at least partially through the ABCA1/Cdc42/cAMP/ Protein kinase A (PKA) pathway

Regulation and Roles of Urocortins in the Vascular System

Urocortins (Ucns) are members of the corticotropin-releasing factor (CRF) family of peptides. Ucns would have potent effects on the cardiovascular system via the CRF receptor type 2 (CRF 2 receptor). Regulation and roles of each Ucn have been determined in the vascular system. Ucns have more potent vasodilatory effects than CRF. Human umbilical vein endothelial cells (HUVECs) express Ucns1-3 mRNAs, and the receptor, CRF 2a receptor mRNA. Ucns1-3 mRNA levels are differentially regulated in HUVECs. Differential regulation of Ucns may suggest differential roles of those in HUVECs. Ucn1 and Ucn2 have strong effects on interleukin (IL)-6 gene expression and secretion in rat aortic smooth muscle A7r5 cells. The increase that we observed in IL-6 levels following Ucn treatment of A7r5 cells suggests that smooth muscle cells may be a source of IL-6 secretion under physiological stress conditions. Ucns are important and unique modulators of vascular smooth muscle cells and act directly or indirectly as autocrine and paracrine factors in the vascular system

2型糖尿病患者において高インスリン血症は肥満，脂質異常症，インスリン抵抗性とは独立して血漿アルドステロン濃度上昇に関与している

The study was to define plasma insulin level with the association of renin-angiotensin-aldosterone system activity in patients with type 2 diabetes. One hundred fi fty type 2 diabetic patients and 24 non-diabetic subjects were studied. There was no statistical diff erence between the two groups in age, gender, the prevalence of hypertension, and serum potassium concentration. Plasma aldosterone concentration(PAC) was signifi cantly higher in type 2 diabetics than that in non-diabetic subjects(10.4±4.9 vs. 7.4±3.7 ng/dl；p=0.004)； however plasma renin activity(PRA) did not diff er signifi cantly between the two groups. In diabetic patients, PAC correlated signifi cantly with body mass index(BMI), fasting plasma insulin(F-IRI), homeostasis model assessment insulin resistance (HOMA-R), urinary C-peptide excretion(U-CPR), triglycerid(e TG), and high-density lipoprotein cholestero(l HDL-C). PRA correlated signifi cantly with F-IRI and HOMA-R, but did not correlate with BMI, U-CPR, TG, and HDL-C. The additional contribution of U-CPR in predicting PAC was signifi cant after adjustment for age, BMI, F-IRI, TG, HDL-C, and PRA(β=0.204, p=0.016). These fi ndings indicate that hyperinsulinemia may aff ect the increase in PAC unrelated with obesity, dyslipidemia, insulin resistance that are components of metabolic syndrome in patients with type 2 diabetes

Non-Sectarian Committee for German Refugee Children, Wagner-Rogers Bill, Memorandum on Resolutions and Congressional Hearing (Box 3, Folder 10)

The Marion E. Kenworthy Papers contain correspondence, newsletters and minutes of meetings of the Non-Sectarian Committee for German Refugee Children, which was established in 1938 to lobby the United States government to allow immigration for refugee children. The collection also contains correspondence, pamphlets, newspaper articles, editorials, and congressional testimony relating to the 1939 Wagner-Rogers Bill authorizing the admittance of German refugee children to the United States as well as correspondence pertaining to this legislation from the Jewish Children's Bureau of Chicago (1939). Among the more important correspondents are Stephen S. Wise, Robert F. Wagner, Justin Wise Polier, Eugene Meyer and Dorothy Canfield Fisher.Digital ImageDigital finding aid