Abstract
Pancreatic islet transplantation has become an established approach to β-cell replacement therapy for the treatment of insulin-deficient diabetes. Recent progress in techniques for islet ...isolation, islet culture, and peritransplant management of the islet transplant recipient has resulted in substantial improvements in metabolic and safety outcomes for patients. For patients requiring total or subtotal pancreatectomy for benign disease of the pancreas, isolation of islets from the diseased pancreas with intrahepatic transplantation of autologous islets can prevent or ameliorate postsurgical diabetes, and for patients previously experiencing painful recurrent acute or chronic pancreatitis, quality of life is substantially improved. For patients with type 1 diabetes or insulin-deficient forms of pancreatogenic (type 3c) diabetes, isolation of islets from a deceased donor pancreas with intrahepatic transplantation of allogeneic islets can ameliorate problematic hypoglycemia, stabilize glycemic lability, and maintain on-target glycemic control, consequently with improved quality of life, and often without the requirement for insulin therapy. Because the metabolic benefits are dependent on the numbers of islets transplanted that survive engraftment, recipients of autoislets are limited to receive the number of islets isolated from their own pancreas, whereas recipients of alloislets may receive islets isolated from more than one donor pancreas. The development of alternative sources of islet cells for transplantation, whether from autologous, allogeneic, or xenogeneic tissues, is an active area of investigation that promises to expand access and indications for islet transplantation in the future treatment of diabetes.
Mid-to-late M stars are opportunistic targets for the study of low-mass exoplanets in transit because of the high planet-to-star radius ratios of their planets. Recent studies of such stars have ...shown that, like their early-M counterparts, they often host multi-resonant networks of small planets. Here, I reanalyze radial velocity measurements of YZ Ceti, an active M4 dwarf for which the HARPS exoplanet survey recently discovered three exoplanets on short-period (P = 4.66, 3.06, 1.97 days) orbits. My analysis finds that the orbital periods of the inner two planets cannot be uniquely determined using the published HARPS velocities. In particular, it appears likely that the 3.06 day period of YZ Ceti c is an alias and that its true period is 0.75 days. If so, the revised minimum mass of this planet is less than 0.6 Earth masses and its geometric transit probability increases to 10%. I encourage additional observations to determine the true periods of YZ Ceti b and c and suggest a search for transits at the 0.75 day period in TESS light curves.
Reactive oxygen species (ROS) are formed by virtually all tissues. In normal concentrations they facilitate many physiologic activities, but in excess they cause oxidative stress and tissue damage. ...Local antioxidant enzyme synthesis in cells is regulated by the cytoplasmic KEAP-1/Nrf2 complex, which is stimulated by ROS, to release Nrf2 for entry into the nucleus, where it upregulates antioxidant gene expression. Major antioxidant enzymes include glutathione peroxidase (GPx), catalase (CAT), superoxide dismutases (SOD), hemoxygenases (HO), and peroxiredoxins (Prdx). Notably, the pancreatic islet β-cell does not express GPx or CAT, which puts it at greater risk for ROS damage caused by postprandial hyperglycemia. Experimentally, overexpression of GPx in β-cell lines and isolated islets, as well as in vivo studies using genetic models of type 2 diabetes (T2D), has demonstrated enhanced protection against hyperglycemia and oxidative stress. Oral treatment of diabetic rodents with ebselen, a GPx mimetic that is approved for human clinical use, reproduced these findings. Prdx detoxify hydrogen peroxide and reduce lipid peroxides. This suggests that pharmacologic development of more potent, β-cell-specific antioxidants could be valuable as a treatment for oxidative stress due to postprandial hyperglycemia in early T2D in humans.
Abstract
Thyroid dysfunction and diabetes mellitus are closely linked. Several studies have documented the increased prevalence of thyroid disorders in patients with diabetes mellitus and vice versa. ...This review critically discusses the different underlying mechanisms linking type 1 and 2 diabetes and thyroid dysfunction to demonstrate that the association of these two common disorders is unlikely a simple coincidence. We assess the current state of knowledge on the central and peripheral control of thyroid hormone on food intake and glucose and lipid metabolism in target tissues (such as liver, white and brown adipose tissue, pancreatic β cells, and skeletal muscle) to explain the mechanism linking overt and subclinical hypothyroidism to type 2 diabetes and metabolic syndrome. We also elucidate the common susceptibility genes and the pathogenetic mechanisms contributing to the autoimmune mechanism involved in the onset of type 1 diabetes mellitus and autoimmune thyroid disorders. An untreated thyroid dysfunction can impair the metabolic control of diabetic patients, and this association can have important repercussions on the outcome of both of these disorders. Therefore, we offer recommendations for the diagnosis, management, and screening of thyroid disorders in patients with diabetes mellitus, including the treatment of diabetic patients planning a pregnancy. We also discuss the major causes of failure to achieve an optimal management of thyroid dysfunction in diabetic patients and provide recommendations for assessing and treating these disorders during therapy with antidiabetic drugs. An algorithm for a correct approach of these disorders when linked is also provided.
The M dwarf star Gliese 581 is believed to host four planets, including one (GJ 581d) near the habitable zone that could possibly support liquid water on its surface if it is a rocky planet. The ...detection of another habitable-zone planet–GJ 581g–is disputed, as its significance depends on the eccentricity assumed for d. Analyzing stellar activity using the Hα line, we measure a stellar rotation period of 130 ± 2 days and a correlation for Hα modulation with radial velocity. Correcting for activity greatly diminishes the signal of GJ 581d (to 1.5 standard deviations) while significantly boosting the signals of the other known super-Earth planets. GJ 581d does not exist, but is an artifact of stellar activity which, when incompletely corrected, causes the false detection of planet g.
This perspective examines the proposition that chronically elevated blood glucose levels caused by type 2 diabetes (T2D) harm body tissues by locally generating reactive oxygen species (ROS). A ...feed-forward scenario is described in which the initial onset of defective beta cell function T2D becomes sustained and causes chronic elevations in blood glucose, which flood metabolic pathways throughout the body, giving rise to abnormally high local levels of ROS. Most cells can defend themselves via a full complement of antioxidant enzymes that are activated by ROS. However, the beta cell itself does not contain catalase or glutathione peroxidases and thereby runs a greater risk of ROS-induced damage. In this review, previously published experiments are revisited to examine the concept that chronic hyperglycemia can lead to oxidative stress in the beta cell, how this relates to the absence of beta cell glutathione peroxidase (GPx) activity, and whether this deficiency might be ameliorated by genetic enrichment of beta cell GPx and by oral antioxidants, including ebselen, a GPx mimetic.
The therapeutic potential of pancreatic islet allotransplantation, in which human donor islets are used, as a treatment for type 1 diabetes (T1D) has fascinated diabetes researchers and clinicians ...for decades. At the same time, the therapeutic potential of total pancreatectomy and islet autotransplantation (TPIAT) (in which one's own islets are used) as a preventive treatment for diabetes in patients who undergo total pancreatectomy for chronic, painful pancreatitis has received relatively less attention. This is ironic, since the latter has been much more effective than the former in terms of successful glucose management and duration of efficacy. The reasons for this disparity can be partially identified. TPIAT receives very little attention in textbooks of internal medicine and general surgery and surprisingly little print in textbooks of endocrinology and transplantation. T1D is much more predominant than TPIAT as a clinical entity. Provision of insulin or replacement of islets is mandatory and a primary goal in T1D. Provision of pain relief from chronic pancreatitis is the primary goal of total pancreatectomy in TPIAT, whereas treatment of diabetes, and certainly prevention of diabetes, has been more of a secondary consideration. Nonetheless, research developments in both fields have contributed to success in one another. In this Perspective, I will provide a brief history of islet transplantation and contrast and compare the procedures of allo- and autoislet transplantation from three major points of view 1) the procedures of islet procurement, isolation, and transplantation; 2) the role and complications of immunosuppressive drugs; and 3) the posttransplant consequences on β- as well as α-cell function.
JCEM Editor's Swan Song: 2015-2019 Robertson, R Paul
The journal of clinical endocrinology and metabolism,
12/2019, Volume:
104, Issue:
12
Journal Article
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