Anti-Inflammatory Effects of Glucagon-Like Peptide-1 Receptor Agonists via the Neuroimmune Axis.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have shown efficacy in the treatment of metabolic disease-related complications, partially attributable to their anti-inflammatory properties. However, the specific cell types and pathways involved in these effects were not fully understood. A recent study by Wong et al. demonstrated the importance of the brain GLP-1R in mediating the anti-inflammatory effects of GLP-1RAs in Toll-like receptor and sepsis-mediated inflammation. In this discussion, we review the existing literature on the action of GLP-1RAs in inflammation and explore the implications of these recent findings.

Clinical Best Practices for Radiation Safety During Lutetium-177 Therapy.

IMPORTANCE: 177 Lu therapy as part of theranostic treatment for cancer is expanding but it can be a challenge for sites with limited radiation protection staff to implement the radiation safety program required for therapeutic nuclear medicine. OBJECTIVE: To increase the adoption of 177 Lu therapy, especially in smaller centers and clinics, by providing a collection of radiation safety best practices and operational experience. To provide a resource for radiation safety officers supporting the implementation of a 177 Lu therapy program. METHODS: A panel of 11 radiation safety professionals representing sites across Canada and the United States with experience delivering 177 Lu therapy was assembled and discussed their responses to a list of questions focused on the following radiation safety topics: facility layout and design; radiation safety program; and drug management and patient care. RESULTS: A comprehensive set of best practice guidelines for clinical radiation safety during 177 Lu therapy has been developed based on the collective operational experience of a group of radiation safety professionals. Significant findings included that 177 Lu therapy is often safely administered in unshielded rooms, that staff radiation exposure associated with 177 Lu therapy is minimal relative to other nuclear medicine programs, and that some relatively simple preparation in advance including papering of common surfaces and planning for incontinence can effectively control contamination during therapy. CONCLUSION: The guidance contained in this paper will assist radiation safety professionals in the implementation of safe, effective 177 Lu therapy programs, even at smaller sites with limited to no experience in therapeutic nuclear medicine.

Investigating the protective effects of estrogen on ß-cell health and the progression of hyperglycemia-induced atherosclerosis.

Sex differences in the prevalence and development of diabetes and associated cardiometabolic complications are well established. The objective of this study was to analyze the effects of estrogen on the maintenance of ß-cell health/function and atherosclerosis progression, using a mouse model of hyperglycemia-induced atherosclerosis, the ApoE-/-:Ins2+/Akita mouse. ApoE-/-:Ins2+/Akita mice exhibit sexual dimorphism in the control of blood glucose levels. Male ApoE-/-:Ins2+/Akita mice are chronically hyperglycemic due to a significant reduction in pancreatic ß-cell mass. Female mice are only transiently hyperglycemic, maintain ß-cell mass, and blood glucose levels normalize at 35 ± 1 days of age. To determine the effects of estrogen on pancreatic ß-cell health and function, ovariectomies and estrogen supplementation experiments were performed, and pancreatic health and atherosclerosis were assessed at various time points. Ovariectomized ApoE-/-:Ins2+/Akita mice developed chronic hyperglycemia with significantly reduced ß-cell mass. To determine whether the observed effects on ovariectomized ApoE-/-:Ins2+/Akita mice were due to a lack of estrogens, slow-releasing estradiol pellets were inserted subcutaneously. Ovariectomized ApoE-/-:Ins2+/Akita mice treated with exogenous estradiol showed normalized blood glucose levels and maintained ß-cell mass. Exogenous estradiol significantly reduced atherosclerosis in both ovariectomized female and male ApoE-/-:Ins2+/Akita mice relative to controls. Together, these findings suggest that estradiol confers significant protection to pancreatic ß-cell health and can directly and indirectly slow the progression of atherosclerosis.NEW & NOTEWORTHY This study examines the effect(s) of estrogen on ß cell and cardiometabolic health/function in a novel mouse model of hyperglycemia-induced atherosclerosis (ApoE-/-:Ins2+/Akita). Using a combination of estrogen deprivation (ovariectomy) and supplementation strategies, we quantify effects on glucose homeostasis and atherogenesis. Our results clearly show a protective role for estrogen on pancreatic ß-cell health and function and glucose homeostasis. Furthermore, estrogen supplementation dramatically reduces atherosclerosis progression in both male and female mice.