Hypothalamic AMP-Activated Protein Kinase Regulates Glucose Production

OBJECTIVE—The fuel sensor AMP-activated protein kinase (AMPK) in the hypothalamus regulates energy homeostasis by sensing nutritional and hormonal signals. However, the role of hypothalamic AMPK in glucose production regulation remains to be elucidated. We hypothesize that bidirectional changes in hypothalamic AMPK activity alter glucose production. RESEARCH DESIGN AND METHODS—To introduce bidirec-tional changes in hypothalamic AMPK activity in vivo, we first knocked down hypothalamic AMPK activity in male Sprague-Dawley rats by either injecting an adenovirus expressing the dominant-negative form of AMPK (Ad-DN AMPK2 [D157A]) or infusing AMPK inhibitor compound C directly into the medio-basal hypothalamus. Next, we independently activated hypotha-lamic AMPK by delivering either an adenovirus expressing the constitutive active form of AMPK (Ad-CA AMPK1312 [T172D]

Quantum Symmetries and Marginal Deformations

We study the symmetries of the N=1 exactly marginal deformations of N=4 Super Yang-Mills theory. For generic values of the parameters, these deformations are known to break the SU(3) part of the R-symmetry group down to a discrete subgroup. However, a closer look from the perspective of quantum groups reveals that the Lagrangian is in fact invariant under a certain Hopf algebra which is a non-standard quantum deformation of the algebra of functions on SU(3). Our discussion is motivated by the desire to better understand why these theories have significant differences from N=4 SYM regarding the planar integrability (or rather lack thereof) of the spin chains encoding their spectrum. However, our construction works at the level of the classical Lagrangian, without relying on the language of spin chains. Our approach might eventually provide a better understanding of the finiteness properties of these theories as well as help in the construction of their AdS/CFT duals.Comment: 1+40 pages. v2: minor clarifications and references added. v3: Added an appendix, fixed minor typo

Central Nervous System (CNS) Nutrient Sensing in Diabetes

An acute increase in hypothalamic glucose and its downstream metabolite lactate lower glucose production (GP) and plasma glucose (PG) levels in normal rodents. However, the effectiveness of this nutrient-sensing mechanism in metabolic disease is unknown. We assessed the effects of intracerebroventricular (i.c.v.) or intra-hypothalamic glucose and lactate on in vivo glucose kinetics in conscious rats. Study I revealed that i.c.v. lactate lowered PG via a suppression of GP in rodents with uncontrolled diabetes and diet-induced insulin resistance. Study II demonstrated that i.c.v. glucose was ineffective at suppressing GP in uncontrolled diabetic rodents or rodents with a prior 24 h whole-body or hypothalamic hyperglycemic insult. When PG levels per se were normalized in diabetic rodents hypothalamic glucose sensing to lower GP was rescued. As such, sustained hyperglycemia per se impairs hypothalamic glucose effectiveness in diabetes. Further studies are necessary to determine defective mechanisms upstream of lactate metabolism hindering CNS glucose sensing.MAS

Tiotropium for the Treatment of Asthma: Patient Selection and Perspectives

Asthma is a chronic disease of airway inflammation with a large global burden. Despite established, guideline-based stepwise therapy, a significant proportion of patients remain symptomatic and poorly controlled. As such, there is a need for additional safe, effective, convenient, and cost-effective therapies that can be broadly applied across a range of asthma phenotypes. Tiotropium is a long-acting muscarinic antagonist (LAMA) that leads to bronchodilation by blocking endogenous acetylcholine receptors in the airways. Tiotropium has long been approved for the treatment of chronic obstructive pulmonary disease, and it has recently been recognized for its safety and efficacy in improving lung function and controlling asthma. Evidence from several Phase III trials in the adult and paediatric population has shown that tiotropium is well tolerated and significantly improves a range of endpoints as an add-on treatment to ICS therapy, regardless of baseline characteristics and clinical phenotypes. Consequently, regulatory authorities worldwide have recently licensed tiotropium as the only LAMA approved for the treatment of asthma. This review provides an overview of safety and efficacy data and discusses the use of tiotropium in patients across the range of asthma severities, ages, and phenotypes

Risk-adjusted performance evaluation in three academic thoracic surgery units using the Eurolung risk models

The objective of this study was to evaluate the performance of 3 thoracic surgery centres using the Eurolung risk models for morbidity and mortality.status: publishe