Progress in research on neuroprotective mechanism of glucagon-like peptide-1 receptor agonists and analogues in Parkinson's disease / 中国生物制品学杂志

@#Parkinson's disease(PD)is the second common neurodegenerative disease that mostly occurs in middle-aged and elderly people. Currently,Levodopa is the main first-line treatment drug,but the long-term efficacy of patients is not good,and even side effects such as“on-off”phenomenon and orthostatic hypotension occur. Glucagon-like peptide-1receptor agonists(GLP-1RA)and analogues are endogenous peptide hormones that can be released into the blood and enter the central nervous system to exert neuroprotection by crossing the blood-brain barrier. Numerous studies have shown that GLP-1RA can improve movement disorders and restore dopaminergic neuron activity in PD. However,the mechanism of GLP-1RA is not yet fully clear. This paper summarized the mechanism of GLP-1RA and its analogues in improving PD movement disorders and restoring dopaminergic neuron activity,and reviewed the aspects of reducing neuroinflammation,inhibiting oxidative stress,inhibiting apoptosis,regulating mitochondrial morphology,increasing neuronal protrusions,enhancing autophagy,and regulating intestinal flora homeostasis,so as to provide new ideas for research of the mechanisms of PD and development of GLP-1RA-related new drugs.

Anti-inflammatory effects of liraglutide on innate lymphoid cells in mice with inflammatory bowel disease / 上海交通大学学报（医学版）

Objective • To investigate the role and mechanism of glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide in dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD). Methods • The drinking water with DSS concentration of 3% was prepared by using DSS and sterile water, and the mice were free to drink for 7 days, to construct IBD model. The experimental mice were randomly divided into four groups with five mice in each group: the control group [drinking sterile water, intraperitoneal injection of phosphate buffered saline (PBS)], the liraglutide group (drinking sterile water, intraperitoneal injection of 0.6 mg/kg liraglutide), the model group (drinking DSS water solution, intraperitoneal injection of PBS) and the treatment group (drinking DSS water solution, intraperitoneal injection of 0.6 mg/kg liraglutide). During the experiment, the fecal morphology, body weight, and colon length were observed. And hematoxylin-eosin (H-E) staining was used to observe the degree of colitis in mice. Flow cytometry was used to detect the proportion of neutrophils and eosinophils, as well as the changes of the innate lymphoid cell (ILC) subsets and function in the colon. Results • Compared with the model group, the symptoms of loose stool and bloody stool were improved, and the shortened colon length was also improved (P=0.007) in the treatment group. H-E staining showed that the infiltration of inflammatory cells in the colon of the treatment group was significantly reduced. Flow cytometry analysis of the colonic lamina propria showed that the proportion of neutrophils in the colon of the treatment group was significantly reduced (P=0.004), and the proportion of eosinophils was also reduced (P=0.002); the proportion of ILC (ILC2) in group 2 decreased (P=0.032), but the proportion of ILC (ILC3) in group 3 increased (P=0.008); the cytokine interleukin-22 secreted by ILC3 was increased (P=0.008). Conclusion • Liraglutide may delay the development of IBD by affecting the proportion of ILC subsets and secretion function.

Efectos cardiovasculares de los nuevos fármacos no insulínicos en diabetes / Cardiovascular effects of new non-insulinic anti-diabetes drugs]

La diabetes mellitus constituye actualmente un grave problema de salud pública a nivel mundial, que incrementa el riesgo de presentar complicaciones tanto microvasculares como macrovasculares. Aunque lograr los objetivos de glucemia recomendados reduce el riesgo de complicaciones microvasculares, el efecto de los fármacos para tratar la hiperglucemia sobre las complicaciones macrovasculares y la muerte cardiovascular es motivo de preocupación. En este contexto, las agencias regulatorias han modificado la normativa para la aprobación de nuevos fármacos en diabetes, de forma que establecen la necesidad de demostrar que son capaces de disminuir la glucemia junto con una evaluación sólida de la seguridad cardiovascular. El objetivo de este trabajo es revisar los efectos cardiovasculares de las nuevas familias de fármacos no insulínicos, en especial en su efecto sobre el riesgo de eventos cardiovasculares mayores. En los últimos años, finalmente, se ha confirmado que algunos fármacos para tratar la diabetes no solo son seguros desde el punto de vista cardiovascular, sino que incluso han mostrado capacidad para reducir el riesgo de enfermedad cardiovascular en la diabetes mellitus tipo 2. La evidencia obtenida ha determinado la actualización de algunas guías terapéuticas vigentes cuando el riesgo cardiovascular debería considerarse una variable fundamental al momento de la elección terapéutica en pacientes con diabetes.

Diabetes mellitus is currently a serious public health problem worldwide, that increases the risk of presenting microvascular and macrovascular complications. Although achieving the recommended blood glucose goals reduces the risk of microvascular complications, the effect of the drugs used to treat hyperglycemia on macrovascular complications and cardiovascular death is a cause for concern. In this context, the regulatory agencies have modified the regulations for the approval of new drugs in diabetes, by adding the need to demonstrate that they are capable of lowering blood glucose levels together with a solid assessment of cardiovascular safety. The objective of this study is to review the cardiovascular effects of the new families of non-insulin drugs, with special emphasis on their effect on the risk of major cardiovascular events. In recent years, it has finally been confirmed that some of the drugs used to treat diabetes are not only safe from a cardiovascular point of view, but have even shown capacity to reduce the risk of cardiovascular disease in type 2 diabetes mellitus. The evidence obtained determined the updating of some current therapeutic guidelines when cardiovascular risk should be considered a fundamental variable at the time of therapeutic choice in patients with diabetes.

Paradigm shift-prospective on anti-diabetic medical treatment strategy based on cardiovascular protection / 中国糖尿病杂志

Diabetes has become one of the most devastating non-communicable chronic diseases worldwide.China has the most diabetes patients in the world,the prevention and control of diabetes face great challenges.The main hazard of diabetes is from its complications;especially the cardiovascular complications that are the leading cause of death in type 2 diabetes patients.With the progress and effort of diabetes treatment,Acute and chronic microvascular complications of diabetes,such as retinopathy,have been significantly reduced over the past few decades.But cardiovascular disease is still remained as the leading cause of premature death.Therefore,with the availability of new medications that could exert cardiovascular-protection and life saving,the future diabetes treatment strategy should change from the current "glucose-centered" approach to "cardiovascular-centered" one with balanced glycemic control.

Mechanism of glucagon-like peptide 1 receptor agonist induced weight loss of mice / 天津医药

Objective To investigate the possible mechanisms of glucagon-like peptide 1 receptor agonists (GLP-1Ra) induced weight loss. Methods High fat diet induced obese c57BL/6 mice were divided into normal control group (N, n=8), high fat feeding group (HF, n=32) and GLP-1Ra group treated with GLP-1Ra (liraglutide 200μg/(kg·d) or 400μg/(kg·d) for 8 weeks). Changes of body weight, blood glucose and three acyl glycosides (TG) levels were observed in three groups. HE staining was used to observe the morphological changes. Immunofluorescence staining and real-time PCR were used to mea?sure the expression of UCP-1. Furthermore, the expression of PGC-1αin protein level was observed to explore the possible mechanism of GLP-1Ra induced browning in white fat (WAT). Results After 8-week liraglutide (Lira) administration, the body weights were significantly reduced in obese mice (P<0.05). The levels of blood glucose and TG were significantly high?er in HF group than those in N group, which reduced significantly in Lira (200μg·kg-1) and Lira (400μg·kg-1) administra?tion groups (P<0.05). HE staining showed adipocytes in perirenal and inguinal subcutaneous adipose tissue partly acquired brown-like morphological characteristics. The expression levels of UCP-1 protein and mRNA and PGC-1αprotein were ele?vated in adipse tissues, which increased more in Lira (400) than those in Lira (200, P<0.05). Conclusion GLP-1Ra can induce weight loss through white fat browning by activation of UCP-1.