Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors, characterized by excessive release of catecholamines (CAs), and manifested as the classic triad of headaches, palpitations, profuse sweating, and a variety of other signs and symptoms. The diagnosis of PPGL requires both evidence of excessive release of CAs and anatomical localization of CA-secreting tumor. Surgery is the mainstay of treatment for all patients with PPGL unless contraindicated. However, without proper preparation, the release of excessive CAs, especially during surgery, can result in lethal cardiovascular complications. Herein, we briefly reviewed the pathogenesis of this disease, discussed the current approaches and evidence available for preoperative management, summarizing the results of the latest studies which compared the efficacies of preoperative management with or without α adrenergic-receptor antagonists, aiming to facilitate better understanding of the preoperative management of PPGL for the physicians.
β Cell apoptosis and dedifferentiation are 2 hotly debated mechanisms underlying β cell loss in type 2 diabetes; however, the molecular drivers underlying such events remain largely unclear. Here, we performed a side-by-side comparison of mice carrying β cell–specific deletion of ER-associated degradation (ERAD) and autophagy. We reported that, while autophagy was necessary for β cell survival, the highly conserved Sel1L-Hrd1 ERAD protein complex was required for the maintenance of β cell maturation and identity. Using single-cell RNA-Seq, we demonstrated that Sel1L deficiency was not associated with β cell loss, but rather loss of β cell identity. Sel1L-Hrd1 ERAD controlled β cell identity via TGF-β signaling, in part by mediating the degradation of TGF-β receptor 1. Inhibition of TGF-β signaling in Sel1L-deficient β cells augmented the expression of β cell maturation markers and increased the total insulin content. Our data revealed distinct pathogenic effects of 2 major proteolytic pathways in β cells, providing a framework for therapies targeting distinct mechanisms of protein quality control.
Adiponectin is essential for the regulation of tissue substrate utilization and systemic insulin sensitivity. Clinical studies have suggested a positive association of circulating adiponectin with healthspan and lifespan. However, the direct effects of adiponectin on promoting healthspan and lifespan remain unexplored. Here, we are using an adiponectin null mouse and a transgenic adiponectin overexpression model. We directly assessed the effects of circulating adiponectin on the aging process and found that adiponectin null mice display exacerbated age-related glucose and lipid metabolism disorders. Moreover, adiponectin null mice have a significantly shortened lifespan on both chow and high-fat diet. In contrast, a transgenic mouse model with elevated circulating adiponectin levels has a dramatically improved systemic insulin sensitivity, reduced age-related tissue inflammation and fibrosis, and a prolonged healthspan and median lifespan. These results support a role of adiponectin as an essential regulator for healthspan and lifespan.
Summary: A network meta‐analysis of randomized controlled trials (RCTs) was performed to determine the hierarchies of different bariatric surgeries in patients with obesity and type 2 diabetes mellitus (T2DM), in terms of diabetes remission and cardiometabolic outcomes. Seventeen RCTs and six bariatric surgeries, including single anastomosis (mini) gastric bypass (mini‐GBP), biliopancreatic diversion without duodenal switch (BPD), laparoscopic‐adjustable gastric banding (LAGB), laparoscopic sleeve gastrectomy (LSG), Roux‐en‐Y gastric bypass (RYGBP), greater curvature plication (GCP) and nonsurgical treatments (NST) were included. Mini‐GBP, BPD, LSG, RYGBP and LAGB (from best to worst), as compared with NST, were all significantly associated with the remission of T2DM. For the follow‐up period > 3 years, BPD, mini‐GBP, RYGBP and LSG (from best to worst) were significantly superior to NST in achieving the remission of T2DM. For secondary outcomes, the overall ranking for bariatric surgeries was RYGBP > BPD > LSG > LAGB after comprehensively weighting glucose, weight, systolic and diastolic pressure, total cholesterol, triglycerides, high‐density lipoprotein cholesterol (HDL‐C) and low‐density lipoprotein cholesterol (LDL‐C). Mini‐GBP has the greatest probability of achieving diabetes remission in adults with obesity and T2DM, yet BPD was the most effective in long‐term diabetes remission. RYGBP appears to be the most favourable alternative treatment to manage patients with cardiometabolic conditions.