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The Discovery and Development of Liraglutide and Semaglutide
We describe one such approach, albumin binding, and explain how it was applied in the development of the human GLP-1 analog liraglutide once daily and, subsequently, semaglutide once weekly. The pharmacology of these two long-acting GLP-1 analogs, in terms of improving glycemic control, reducing body weight and decreasing cardiovascular (CV) risk, is also reviewed, together with some novel biology. In addition, we describe the importance of accurate target (GLP-1 receptor) tissue expression analysis. Now an established class of agents, GLP-1-based therapies represent a significant advance in the treatment of T2D. All curr...
Source: Frontiers in Endocrinology - April 11, 2019 Category: Endocrinology Source Type: research

Orexin-A Prevents Lipopolysaccharide-Induced Neuroinflammation at the Level of the Intestinal Barrier
We examined a possible protective effect of OX-A against LPS-induced ROS formation and microglia activation. To mimic in vitro the connection between gut and brain and to study the putative effect on the cortical microglia, we used a co-culture of Caco-2 cells and primary cortical microglia with Caco-2 cells placed at the apical side of a transwell and primary cortical microglia at the basolateral side. All treatments used to study the apical vs. basal connection were applied to the apical compartment. We used DHR (10 μM, 20 min), a cell-permeable fluorogenic probe useful for the detection of ROS formation, to dete...
Source: Frontiers in Endocrinology - April 9, 2019 Category: Endocrinology Source Type: research

Cardiovascular Programming During and After Diabetic Pregnancy: Role of Placental Dysfunction and IUGR
This study demonstrated that the incidence of ischemic heart disease and death were three times higher among men with low birth weight compared to men with high birth weight (5). Epidemiological investigations of adults born at the time of the Dutch famine between 1944 and 1945 revealed an association between maternal starvation and a low infant birth weight with a high incidence of hypertension and coronary heart disease in these adults (23). Furthermore, Painter et al. reported the incidence of early onset coronary heart disease among persons conceived during the Dutch famine (24). In that regard, Barker's findin...
Source: Frontiers in Endocrinology - April 8, 2019 Category: Endocrinology Source Type: research