Advances on cardiovascular effects of GLP-lRAs / 中国药理学通报

Glucagon-like peptide-1 ( GLP-1 ) is secreted by gut enteroendocrine cells. GLP-1 receptor agonists ( GLP-1 RAs) control glucose-related augmentation of insulin and suppress glu-cagon secretion. GLP-lRAs also inhibit gastric emptying, food intake and limit weight gain. In the past decade, significant progresses have been made in the investigation on the effects of GLP-1 RAs on cardiovascular system. The potential advantages of oral small-molecule GLP-1 RAs could improve the application of this class of drugs. This review highlights the multiple cardiovascular profiles of GLP-1 RAs in the treatment of cardiovascular diseases to provide new insights into cardiovascular benefits of GLP-1 RAs.

Cost-utility analysis of dorzagliatin combined with metformin in the treatment of type 2 diabetes mellitus patients with poor glycemic control with metformin / 中国药房

OBJECTIVE To assess the long-term cost-effectiveness of five glucagon-like peptide-1 receptor agonists （GLP- 1RAs） in the treatment of poorly controlled type 2 diabetes mellitus （T2DM） treated with metformin. METHODS Baseline data from patients in previously published meta-analysis and included randomized controlled trials （RCTs） were extracted to predict survival， long-term efficacy， and costs for each group using the United Kingdom prospective diabetes study outcome model 2.1. The cost-effectiveness of 5 GLP-1RAs （liraglutide， lixisenatide， exenatide， dulaglutide， and semaglutide） was analyzed by cost- utility analysis. Sensitivity analysis and scenario analysis were also performed to verify the uncertainty of basic analysis results. RESULTS A total of 21 RCTs with 6 796 patients were included. Survival analysis curves showed the superiority of semaglutide in reducing the risk of death from cardiovascular disease and dulaglutide in reducing the risk of all-cause mortality over other GLP- 1RAs. The cost-utility analysis showed that the five drugs were economically superior to inferior in the order of lixisenatide， semaglutide， exenatide， dulaglutide， and liraglutide； one-way and probabilistic sensitivity analyses indicated that the results were robust. The scenario analysis results indicated that the price of semaglutide should decrease by at least 54.64% to 369.21 yuan， which is cost-effectiveness compared to lixisenatide. CONCLUSIONS For T2DM patients in China with poor glycemic control after treatment with metformin， lixisenatide and semaglutide may be considered as the preferred regimen.

Cost-utility analysis of 5 kinds of GLP-1RAs in the treatment of poorly controlled type 2 diabetes mellitus treated with metformin / 中国药房

OBJECTIVE To assess the long-term cost-effectiveness of five glucagon-like peptide-1 receptor agonists （GLP- 1RAs） in the treatment of poorly controlled type 2 diabetes mellitus （T2DM） treated with metformin. METHODS Baseline data from patients in previously published meta-analysis and included randomized controlled trials （RCTs） were extracted to predict survival， long-term efficacy， and costs for each group using the United Kingdom prospective diabetes study outcome model 2.1. The cost-effectiveness of 5 GLP-1RAs （liraglutide， lixisenatide， exenatide， dulaglutide， and semaglutide） was analyzed by cost- utility analysis. Sensitivity analysis and scenario analysis were also performed to verify the uncertainty of basic analysis results. RESULTS A total of 21 RCTs with 6 796 patients were included. Survival analysis curves showed the superiority of semaglutide in reducing the risk of death from cardiovascular disease and dulaglutide in reducing the risk of all-cause mortality over other GLP- 1RAs. The cost-utility analysis showed that the five drugs were economically superior to inferior in the order of lixisenatide， semaglutide， exenatide， dulaglutide， and liraglutide； one-way and probabilistic sensitivity analyses indicated that the results were robust. The scenario analysis results indicated that the price of semaglutide should decrease by at least 54.64% to 369.21 yuan， which is cost-effectiveness compared to lixisenatide. CONCLUSIONS For T2DM patients in China with poor glycemic control after treatment with metformin， lixisenatide and semaglutide may be considered as the preferred regimen.

Recomendaciones de expertos acerca del uso de teduglutide en pacientes pediátricos con sindrome de intestino corto / Expert recommendations on the use of teduglutide in pediatric patients with short bowel syndrome

Resumen El síndrome de intestino corto es una entidad de baja incidencia en los pacientes pediátricos, pero se asocia con elevadas tasas de morbimortalidad. El abordaje de estos pacientes por un equipo interdisciplinario de expertos enfocados en la rehabilitación intestinal mejora los resultados a corto y a largo plazo. Entre los recursos disponibles para el tratamiento se incluye el teduglutide, un análogo del péptido similar al glucagón tipo 2 (GLP-2) elaborado mediante técnicas recombinantes. Por medio de la aplicación del método Delphi, a partir de la evidencia disponible y de la experiencia de los autores, se proponen recomendaciones para el uso de teduglutide, dirigidas a los profesionales de la salud que tratan a los pacientes pediátricos con síndrome de intestino corto, así como a las autoridades sanitarias.

Abstract Short bowel syndrome is a low-incidence disorder among pediatric patients, but it is associated with high morbidity and mortality rates. Management of these patients by an interdisciplinary team of experts focused on intestinal rehabilitation improves short- and long-term outcomes. Available resources for treatment include teduglutide, a glucagon-like peptide type 2 (GLP-2) analog made by recombinant techniques. Considering the available evi dence and the authors' experience, Delphi-based recommendations for the use of teduglutide are suggested for healthcare professionals who treat pediatric patients with short bowel syndrome, as well as for health authorities.

La semaglutida en el tratamiento de las personas con diabesidad / Semaglutide in the Treatment of Diabesity Individuals

Introducción: La semaglutida es un fármaco que contribuye a la liberación de insulina por el páncreas y a la supresión del apetito por lo que lo convierte en un importante candidato para ser usado en el tratamiento de la diabesidad. Objetivo: Describir el efecto de la semaglutida en el tratamiento de las personas con diabesidad. Métodos: Se revisó la literatura publicada en el período comprendido de enero-febrero de 2021. Las palabras clave utilizadas fueron obesidad; diabetes mellitus; diabesidad; semaglutida; análogo del péptido similar al glucagón tipo 1. Se utilizaron como motores de búsqueda las bases de datos de Google Académico, PubMed y SciELO. Se evaluaron diferentes trabajos de revisión, investigación y páginas web que tenían menos de 10 años de publicados en idioma español, portugués o inglés, y que por el título trataban el tema de estudio. Fueron excluidos los artículos que no abordaron la relación entre diabetes y obesidad, así como el tratamiento con análogos del péptido similar al glucagón tipo 1. Esto permitió la consulta de 84 artículos, de los cuales 59 fueron referenciados. Conclusiones: El empleo de semaglutida favorece una mejor evolución en paciente con diabesidad, como complemento de una dieta y una actividad física adecuada. Al optimizar el control glucémico, contribuir a la pérdida de peso y a la mejoraría de ciertas comorbilidades, entre ellas la salud cardiovascular(AU)

Introduction: Semaglutide is a drug that contributes to the release of insulin from the pancreas and suppresses appetite, which makes it an important candidate for treating diabesity. Objective: To describe the role of semaglutide in the treatment of diabesity individuals. Methods: The necessary information to write this article was obtained in the 2022 two-month period January-February. The keywords used were obesity; Mellitus diabetes; diabesity; semaglutide; type 1 glucagon-like peptide analogue. The search engines corresponding to the Google Scholar, PubMed and SciElO databases were used. Different review, research and web pages were evaluated, which in general were published no more than 10 years ago, in Spanish, Portuguese or English and which dealt with the subject of study by title. Articles that did not address the relationship between diabetes and obesity, as well as treatment with glucagon-like peptide 1 analogues, were excluded. This allowed the consultation of 84 articles, 59 of them were referenced. Conclusions: The use of semaglutide, as a complement to a diet and physical activity appropriate to the needs of patients with diabesity, brought about several effects that favor better evolution of this health problem, by optimizing glycemic control, contributing to the loss of weight and the improvement of certain comorbidities, including cardiovascular health(AU)

The efficacy of liraglutide combined with intragastric balloon on weight loss

SUMMARY OBJECTIVE: Intragastric balloon placement is an effective method for weight reduction. The aim of this study was to evaluate the efficacy of combining liraglutide with intragastric balloon. METHODS: Initially, demographic data of patients such as age, gender, comorbid diseases, adverse events, initial weight, height, body mass index, percent body fat, and waist-hip ratio were collected. Weight, body mass index, percent body fat, and waist-hip ratio were measured in the second, third, fourth, fifth, and sixth months. Then, intragastric balloon was removed and liraglutide was stopped. RESULTS: A total of 50 patients were included in the study, of whom 28 (56%) were in Group A (intragastric balloon) and 22 (44%) were in Group B (plus liraglutide). Weight change at the time of balloon removal was higher in Group B [median weight change 13.8 (7.8 min to 16.8 max) versus 7.9 (4.8 min to 11.8 max); p<0.01]. When the weight, percent body fat, body mass index, and waist-hip ratio changes were compared according to gender, no significant difference was observed in the groups. Comorbid diseases were hypertension in 7 patients (4 in Group A and 3 in Group B) and diabetes in 9 patients (5 in Group A and 4 in Group B). No statistical significance was found. CONCLUSION: Liraglutide has benefits in terms of weight, percent body fat, and body mass index reduction when administered with intragastric balloon.

Design and oral hypoglycemic activity of novel oral hypoglycemic peptide ODA / 中国药科大学学报

@#Incretin promotes insulin secretion through a glucose-dependent mechanism, involving glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Therefore, their correspondingly specific receptors GLP-1R and GIPR are suitable targets for the treatment of type 2 diabetes. Based on the oral hypoglycemic peptide OHP2 designed by our team, we further designed a new oral hypoglycemic peptide, ODA to reduce glucose. Compared with OHP2, ODA exhibited better lipophilicity as well as the enhanced endocytosis and transcytosis in Caco-2 cells. In addition, ODA remained the ability to activate GLP-1R and enhanced the binding ability to GIPR. The hypoglycemic efficacy of the low-dose ODA (0.53 mg/kg) is comparable to that of OHP2 (1.06 mg/kg). These results indicated that ODA could be a new oral drug with potential for the treatment of type 2 diabetes.

Effect of Zuogui Jiangtang Tongmai Prescription on SCFAs/GPR43/GLP-1/GLP-1R Signaling Pathway in Rats with Diabetes Mellitus Complicated with Cerebral Infarction / 中国实验方剂学杂志

ObjectiveTo explore the potential mechanism of Zuogui Jiangtang Tongmai prescription （ZJT） in the treatment of diabetes mellitus complicated with cerebral infarction （DM-CI） in rats based on the short-chain fatty acids （SCFAs）/G protein-coupled receptor 43 （GPR43）/glucagon-like peptide-1 （GLP-1）/GLP-1 receptor （GLP-1R） signaling pathway. MethodSixty SD rats were randomly divided into sham operation group， model group， low- and high-dose ZJT groups （12， 24 g·kg-1）， western medicine group （140 mg·kg-1 pioglitazone metformin tablets + 27 mg·kg-1 enteric-coated aspirin tablets）. Except for the sham operation group， all other groups were fed a high-sugar high-fat diet for 4 weeks and then subjected to intraperitoneal injection of 1% streptozotocin at 35 mg·kg-1 combined with middle cerebral artery occlusion （MCAO） to establish a DM-CI rat model. The corresponding interventions were performed with distilled water， low-dose ZJT， high-dose ZJT， pioglitazone metformin tablets， and enteric-coated aspirin tablets. After surgery， National Institutes of Health Stroke Scale （NIHSS） scoring and triphenyltetrazolium chloride （TTC） staining to measure the rat's cerebral infarct volume were carried out. Random blood glucose levels were measured， and hematoxylin-eosin （HE） staining was used to observe histopathological changes in rat brain tissues. Gas chromatography was employed to detect the content of SCFAs in the cecum contents. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure serum GLP-1 level. Western blot was used to detect the protein expression of GPR43 in rat ileal tissues and GLP-1R in the ischemic brain tissues. ResultCompared with the sham operation group， the model group showed significantly increased NIHSS scores， random blood glucose levels， and cerebral infarct volumes （P<0.01）， and significantly decreased SCFAs content， GLP-1 levels， and GPR43 and GLP-1R protein expression （P<0.01）. Compared with the model group， the high-dose ZJT group and the western medicine group exhibited significantly reduced NIHSS scores， random blood glucose levels， and cerebral infarct volumes （P<0.05， P<0.01）， and significantly increased SCFAs content， GLP-1 levels， and GPR43 and GLP-1R protein expression （P<0.01）. ConclusionZJT can improve glucose metabolism disorder and reduce neurological damage in DM-CI rats， and its mechanism may be related to the increase in SCFAs content and the upregulation of the GPR43/GLP-1/GLP-1R signaling pathway.

Effects of glucagon-like peptide-1 on male reproductive function / 中华内分泌代谢杂志

With the younger onset of diabetes, the reproductive dysfunction caused by diabetes has received widespread attention. Hyperglycemia and insulin resistance, the main features of diabetes, are high-risk factors for male reproductive dysfunction. Obesity, the common co-morbidity of diabetes, may aggravate the progression of reproductive dysfunction. Glucagon-like peptide-1(GLP-1) and its receptor agonists improve the overall health status by lowering blood glucose, reducing body weight, and inhibiting inflammatory response, which indirectly exerts protective effects on the reproductive system. GLP-1 also protects reproductive function by regulating the neuroendocrine function, and directly acting on the supporting cells and interstitial cells of the testis. However, some studies did not find the protective effects. High-quality clinical studies are needed. GLP-1 receptor agonists may be a therapeutic option to improve reproductive dysfunction in diabetic men.

Glucagon-like peptide-1 receptor agonists and glycemic management in non-critical hospitalized patients / 中华内分泌代谢杂志

In recent years, with the continuous development of glucagon-like peptide-1 receptor agonists(GLP-1RA), its role in the management of blood glucose in hospitalized patients has been explored. GLP-1RA can not only control blood glucose in non-critically ill hospitalized patients, but also inhibit appetite, delay gastric emptying, protect nerves, anti-inflammation, reduce systolic blood pressure and blood lipids. At the same time, many studies have found that it can also improve cardiovascular and renal outcomes and reduce the risk of hospitalization complications. Therefore, this paper analyzes the role of GLP-1RA in glycemic management by reviewing domestic and international studies, consensus and guidelines related to inpatient blood glucose management, and helps to better manage blood glucose of patients in non-critical care setting.

Evaluation of monitoring on serum silent information regulator-related enzyme 3, glucagon-like peptide-1 and angiopoietin-like protein 4 in patients with acute ischemic stroke / 中国医师进修杂志

Objective:To investigate the value of monitoring on serum silent information regulator-related enzyme 3 (SIRT3), glucagon-like peptide-1 (GLP-1) and angiopoietin-like protein 4 (ANGPTL4) in patients with acute ischemic stroke (AIS).Methods:Eighty patients with AIS who treatment in Qiongzhong Li and Miao Autonomous County People′s Hospital from May 2019 to April 2022 were selected retrospectively as the observation group, and 60 healthy volunteers who underwent physical examination during the same period were selected as the normal control group. The levels of serum SIRT3, GLP-1, and ANGPTL4 between the two groups were compared. The neurological deficit degree of AIS patients was evaluated by National Institutes of Health Stroke Scale(NIHSS) and the correlation of SIRT3, GLP-1 and ANGPTL4 with neurological deficit degree were analyzed. The levels of serum SIRT3, GLP-1 and ANGPTL4 before and after treatment and their difference value were compared between different clinical outcome of AIS patients, the risk factors for poor clinical outcome of AIS patients were analyzed by Logistic regression analysis, the value of prediction was analyzed by receiver operating characteristic (ROC) curve.Results:The level of serum GLP-1 in the observation group was lower than that in the normal control group: (50.37 ± 5.69) nmol/L vs. (34.89 ± 4.26) nmol/L; and the levels of serum SIRT3 and ANGPTL4 in the observation group were higher than those in the normal control group: (50.37 ± 5.69) ng/L vs. (34.89 ± 4.26) ng/L, (15.07 ± 3.12) μg/L vs. (11.15 ± 2.63) μg/L, there were statistical differences ( P<0.05). The results of correlation analysis showed that the levels of serum SIRT3 and ANGPTL4 were positively correlated with the degree of neurological impairment in AIS patients( r = 0.631, 0.776, P<0.05), and the level of serum GLP-1 was negatively correlated with the degree of neurological impairment in AIS patients ( r = - 0.693, P<0.05). After treatment, 66 patients obtained good clinical outcome, the good outcome rate was 82.50%(66/80). The levels of serum SIRT3 and ANGPTL4 in the poor clinical outcome patients were higher than those in the good clinical outcome patients: (41.33 ± 4.74) ng/L vs. (37.82 ± 4.05) ng/L, (12.98 ± 2.17) μg/L vs. (11.69 ± 2.06) μg/L; the level of serum GLP-1 in the poor clinical outcome patients was lower than that in the good clinical outcome patients: (592.33 ± 98.44) nmol/L vs. (709.41 ± 125.31) nmol/L; the difference value of SIRT3, GLP-1 and ANGPTL4 before and after treatment in the poor clinical outcome patients were lower than those in the good clinical outcome patients: (10.22 ± 2.05) ng/L vs. (12.31 ± 2.94) ng/L, (268.21 ± 70.12) nmol/L vs. (379.92 ± 85.33) nmol/L, (2.18 ± 0.65) μg/L vs. (3.36 ± 0.94) μg/L, there were statistical differences ( P<0.05). The results of Logistic regression analysis showed that differences value of SIRT3, GLP-1 and ANGPTL4 before and after treatment were all independent influencing factors of poor clinical outcome in patients with AIS ( P<0.05). The results of ROC curve analysis showed that the area under the curve (AUC) of differences value of SIRT3, GLP-1 and ANGPTL4 before and after treatment in predicting poor clinical outcome were 0.701, 0.758 and 0.844, respectively, and had certain predictive value, the AUC of joint evaluation was the largest (0.912). Conclusions:The levels of serum SIRT3 and ANGPTL4 in patients with AIS are increased, and the level of serum GLP-1 is decreased, and they are related to the degree of neurological deficit. Clinical monitoring of their level changes is helpful for clinical evaluation of the clinical outcome of patients with AIS.

Tirzepatide: A new glucagon-like peptide-1 receptor/glucose-dependent insulinotropic peptide receptor dual agonist / 中国临床药理学与治疗学

Tirzepatide is the first-in-class dual agonist of glucagon-like peptide-1 (GLP-1) receptor and glucose-dependent insulinotropic peptide (GIP) receptor, which plays a variety of physiological effects by imitating natural GLP-1 and GIP. In the completed large phase III series of clinical studies of SURPASS and SURMOUNT, Tirzepatide has demonstrated excellent effects in decreasing glycosylated hemoglobin, reducing weight, improving blood lipid and other metabolic indicators, and is superior to the currently approved GLP-1 receptor agonist. Gastrointestinal reaction is the most common adverse event of the drug, which is generally mild to moderate, and decreases with continuous administration. On May 13, 2022, Tirzepatide was approved for listing by FDA, the current indication is to improve glycemic control of adult patients with type 2 diabetes (T2D) as an adjunct of diet and exercise. In addition to T2D and obesity, there are also extensive and in-depth studies on other metabolic fields. This paper makes a systematic overview of this.

Regulation of gluconeogenesis in liver, kidney and intestine by glucagon / 中国药理学通报

Aim To investigate the regulatory effect of glucagon on gluconeogenesis in liver, kidney and intes¬tine during different fasting periods and the underlying mechanism. Methods The 8-week-old male C57BIV 6J mice were randomly divided into six groups ( n = 6) :control group, control + glucagon group, fasting 18 h group, fasting 18 h + glucagon group, fasting 36 h group, and fasting 36 h + glucagon group. Glucose, triglyceride ( TG) and free fatty acids ( FFAs ) kits were used to detect their serum contents in mouse in-traperitoneal injection of glucagon at different fasting time points. Besides, liver/muscle glycogen assay kit and PAS staining were used to detect the glycogen con¬tents in liver tissue. RT-PCR method was used to observe the effects of glucagon on the gene expressions of peroxisome proliferators-activated receptor y coactivator la (PGC-1α), glucose-6-phosphatase (G6Pase) and phosphoenol pyruvate carboxykinase 1 (PEPCK) in liver, kidney and intestine of mice at different fasting time. Western blot was employed to detect the protein expressions of PGC-1α, G6Pase, PEPCK, phosphoryl-ase protein kinase A ( p-PKA) , protlein kinase A (PKA) , phosphorylase cAMp-response element binding protein (p-CREB) and cAMp-response element binding protein (CREB) in liver, kidney and intestine of mice were. Results (1) Glucagon increased the serum glucose level, reduced serum TG and FFAs levels, and reduced the hepatic glycogen content. (2) Glucagon promoted gluconeogenesis via upregulation of PGC-1α. On the stimulation of glucagon, PGC-1α gene and protein expressions in liver were significantly raised by glucagon when the mice were fasted 18 h and 36 h, while the gene and protein expressions of PGC-1α in kidney were obviously up-regulated by glucagon after fasting 18 h. However, PGC-1α gene and protein expressions in intestine were significantly elevated by glucagon at 36 h after fasting. (3 ) Glucagon induced gene and protein expressions of gluconeogenesis-related enzymes G6Pase and PEPCK in liver, kidney and intestine after fasting. (4 ) Glucagon upregulated p-PKA/PKA and p-CREB/CREB in liver. Conclusions Glucagon shows temporal difference in the gluconeo-genic response of liver, kidney and intestine in mice. Glucagon promotes the gene and protein expressions of key gluconeogenic enzymes G6Pase and PEPCK by increasing PGC-1α gene and protein expression, and thus increasing fasting blood glucose. Besides, glucagon promotes hepatic gluconeogenesis via PKA/CREB signaling pathway.

Role and mechanism of glucagon-like peptide-1 in depression / 中国药理学通报

Glucagon-like peptide-1 (GLP-1) is a major hormone of incretin hormone and gut-brain axis, which is related to the control of energy homeostasis and the occurrence of obesity. In addition to suppressing appetite, GLP-1 has neuroprotective effects by acting on areas of the brain involved in stress response and mood regulation. Depression is a common mental disease, and GLP-1 is closely related to depression. This article reviews the role and mechanism of GLP-1 in depression.

A cell model for high-throughput screening GLP-1 receptor agonists / 中国药理学通报

Aim To establish a high-throughput screening cell model for GLP-1 receptor agonists. Methods A pEGFP-GLP-1R-3 C recombinant plasmid was constructed and transfected into HEK293T cells. The cells were screened with G418 and flow cytometry. The established stable cell line was named HEK293TGLP-lR-3C-eGFP cell line. The expression level of GLP-1 R-3C-eGFP protein was confirmed by Western blotting and laser confocal microscopy. Then cyclic adenosine monophosphate (cAMP) response element reporter gene was transfected into the HEK293T-GLP-lR-3C-eGFP cells. The luminescence values were detected by One-Step Luciferase Reporter Gene Assay Kit after stimulation with different concentrations of GLP-1 peptide. The luminescence values reflected the cellular cAMP level, which was verified using the cAMP kit (E L I S A). Results HEK293T-GLP-lR-3C-eGFP cell line was successfully constructed. The relative light unit change trend after stimulation with different concentrations of GLP-1 was similar to that of the cellular cAMP level change trend. The value of Z' in this experiment was 0.52. Conclusions A recombinant HEK293T cell line is established, which can be used for high-throughput screening of GLP-1 receptor agonists.

Construction of a 10rolGLP-1-expressing glucose-lowing Saccharomyces cerevisiae by CRISPR/Cas9 technique / 生物工程学报

To develop a novel glucose-lowering biomedicine with potential benefits in the treatment of type 2 diabetes, we used the 10rolGLP-1 gene previously constructed in our laboratory and the CRISPR/Cas9 genome editing technique to create an engineered Saccharomyces cerevisiae strain. The gRNA expression vector pYES2-gRNA, the donor vector pNK1-L-PGK-10rolGLP-1-R and the Cas9 expression vector pGADT7-Cas9 were constructed and co-transformed into S. cerevisiae INVSc1 strain, with the PGK-10rolGLP-1 expressing unit specifically knocked in through homologous recombination. Finally, an S. cerevisiae strain highly expressing the 10rolGLP-1 with glucose-lowering activity was obtained. SDS-PAGE and Western blotting results confirmed that two recombinant strains of S. cerevisiae stably expressed the 10rolGLP-1 and exhibited the desired glucose-lowering property when orally administered to mice. Hypoglycemic experiment results showed that the recombinant hypoglycemic S. cerevisiae strain offered a highly hypoglycemic effect on the diabetic mouse model, and the blood glucose decline was adagio, which can avoid the dangerous consequences caused by rapid decline in blood glucose. Moreover, the body weight and other symptoms such as polyuria also improved significantly, indicating that the orally hypoglycemic S. cerevisiae strain that we constructed may develop into an effective, safe, economic, practical and ideal functional food for type 2 diabetes mellitus treatment.

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.

A cross-sectional study to assess beta-cell function in individuals with recently diagnosed young-onset type 2 diabetes mellitus and its’ complications / Journal of the ASEAN Federation of Endocrine Societies

Objective@#The primary objective was to assess beta-cell function of recently-diagnosed young-onset type 2 diabetes mellitus (T2DM) individuals using basal and stimulated C-peptide levels. The secondary objective was to examine the association between C-peptide with metabolic factors and diabetes complications.@*Methodology@#A cross-sectional study was conducted for young-onset T2DM individuals aged 18-35 years with a disease duration of not more than 5 years. Plasma C-peptide was measured before and after intravenous glucagon injection. Demographic data, medical history and complications were obtained from medical records and clinical assessment. Continuous data were expressed as median and interquartile range (IQR). Categorical variables were described as frequency or percentage. Multivariable linear regression analysis was used to determine factors associated with C-peptide levels.@*Results@#113 participants with young-onset T2DM with a median (IQR) age of 29.0 (9.5) years and 24 (36) months were included in this study. The median (IQR) basal and stimulated C-peptide was 619 (655) pmol/L and 1231 (1024) pmol/L. Adequate beta-cell function was present in 78-86% of the participants based on the basal and stimulated C-peptide levels. We found hypertension, obesity and diabetic kidney disease (DKD) to be independently associated with higher C–peptide levels. In contrast, females, smokers, those on insulin therapy and with longer duration of disease had lower C–peptide levels.@*Conclusion@#Most recently diagnosed young-onset T2DM have adequate beta-cell function. Elevated C-peptide levels associated with obesity, hypertension and diabetic kidney disease suggest insulin resistance as the key driving factor for complications.

Medication guidelines for glucagon-like peptide-1 receptor agonist （2023 edition） / 中国药房

The prevalence of diabetes in China is increasing year by year， and has become a health issue of close concern to the whole society. Glucagon-like peptide-1 （GLP-1） receptor agonist （GLP-1RA）， as a new class of glucose-lowering drugs， is now widely used in the treatment of type 2 diabetes mellitus （T2DM） because of its significant glucose-lowering efficacy and low risk of hypoglycemia. As the level of evidence for its effects on improving cardiovascular system and renal protection and reducing body mass continues to improve， its status in the treatment guidelines for T2DM is gradually increasing. Currently， nine GLP-1RA drugs have been approved for the clinical treatment of T2DM in China. Although all of these drugs exert hypoglycemic effects based on the activation of GLP-1 receptors in the body， the differences in their own structures and natural GLP-1 amino acid homology lead to large differences in pharmacokinetic parameters and clinical efficacy among different analogs. In order to enable clinicians and pharmacists to have a full understanding of the characteristics and clinical evidence of these analogs and to better perform their therapeutic effects， Liaoning Provincial Pharmaceutical Society organized clinical medicine and pharmacy experts to develop a medication guide for nine GLP-1RA drugs to provide a reference for clinical medication needs and promote rational and standardized use by compiling and summarizing the pharmacological characteristics， clinical applications， adverse reactions， interactions， the medications in special populations and medication management.

Cinnamomi Cortex Regulates Incretin Effect in Diabetic Rats / 中国实验方剂学杂志

ObjectiveTo observe the pharmacodynamic effects of Cinnamomi Cortex on the incretin effect in the rat model of diabetes mellites （DM） induced by streptozotocin （STZ） and explore the underlying mechanism from glucagon-like peptide-1 （GLP-1） and dipeptidyl peptidase-4 （DPP-4）. MethodForty SD rats were randomly assigned into blank， model， sitagliptin （0.1 g·kg-1）， and low- and high-dose Cinnamomi Cortex （0.45 and 0.9 g·kg-1， respectively） groups. The DM rat model was established by a high-fat diet combined with intraperitoneal injection of 40 mg·kg-1 STZ in other groups except the blank group. The intervention lasted for 8 weeks. The status， body weight， water intake， food intake， and fasting blood glucose （FBG） of the rats were observed and determined. Hematoxylin-eosin staining was employed to reveal the pathological changes of the pancreas， and immunohistochemistry to detect the expression of glucagon in the pancreas. Biochemical assay was employed to measure the serum levels of lipid metabolism indexes such as total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL）. Enzyme-linked immunosorbent assay was employed to determine the levels of glycosylated hemoglobin， insulin， glucagon， GLP-1， and glucose-dependent insulinotropic polypeptide （GIP） in rat serum， and Western blot to determine the protein levels of GLP-1 and DPP-4 in the pancreas. ResultAfter 8 weeks of intervention， the model group showed higher body weight， FBG， TC， TG， LDL， glycosylated hemoglobin， glucagon， insulin， and insulin resistance index and lower HDL， GLP-1， and GIP than the blank group （P<0.05， P<0.01）. The Cinnamomi Cortex groups showed lower body weight， FBG， TC， TG， LDL， glycosylated hemoglobin， glucagon， insulin， and insulin resistance index and higher HDL， GLP-1， and GIP than the model group （P<0.05， P<0.01）. The Cinnamomi Cortex groups showed recovered morphology of islet cells and no nucleus aggregation. Compared with the model group， the Cinnamomi Cortex groups showed declined levels of glucagon in the center of islet cells. Compared with the blank group， the model group showed up-regulated protein level of DPP-4 and down-regulated protein level of GLP-1 （P<0.01）. Compared with the model group， the high-dose Cinnamomi Cortex groups showed down-regulated protein level of DPP-4 and up-regulated protein level of GLP-1 （P<0.05）. ConclusionCinnamomi Cortex may reduce blood glucose and improve incretin effect to lower the blood glucose level by regulating DPP-4 and GLP-1 in DM rats.