The GLP-1 receptor agonist exenatide ameliorates neuroinflammation, locomotor activity, and anxiety-like behavior in mice with diet-induced obesity through the modulation of microglial M2 polarization and downregulation of SR-A4

Lin, Ming‐Hong; Cheng, Po Ching; Hsiao, Pi‐Jung; Chen, Szu-Chia; Hung, Chih‐Hsing; Kuo, Chao-Hung; Huang, Shau‐Ku; Chiou, Hsin-Ying Clair

doi:10.1016/j.intimp.2022.109653

Cited by 10 publications

(6 citation statements)

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“…Diabetes deleteriously affects microglial function and results in cognitive impairment in both mouse models [ 11 , 42 , 43 ] and patients with T2DM [ 12 , 13 , 14 ]. Moreover, an HG environment elevated the intracellular ROS levels and triggered inflammatory responses in the microglia, which were implicated in several pathways including NF-κB signaling [ 17 , 18 ], p38 and SAPK/JNK MAPK pathways [ 19 ], and NLRP3 inflammasome activation [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms underlying diabetes-related cognitive impairment have not been fully elucidated; however, growing evidence suggests the involvement of pathological processes of multifactorial pathways, such as oxidative stress, cerebrovascular damage, and central insulin resistance, in the development of neurodegeneration in the brain [ 6 , 7 , 8 , 9 ]. Recent preclinical studies using a mouse model of obesity/diabetes have revealed that diabetic conditions exacerbate neurotoxic mediators in the brain, including oxidative stress [ 10 ], microglial activation [ 10 , 11 ], and neuroinflammation [ 10 , 11 ], thereby resulting in cognitive impairment [ 10 , 11 ]. Furthermore, these disease manifestations improved along with glucose metabolism following the administration of glucagon-like peptide (GLP)-1 receptor agonists [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recent preclinical studies using a mouse model of obesity/diabetes have revealed that diabetic conditions exacerbate neurotoxic mediators in the brain, including oxidative stress [ 10 ], microglial activation [ 10 , 11 ], and neuroinflammation [ 10 , 11 ], thereby resulting in cognitive impairment [ 10 , 11 ]. Furthermore, these disease manifestations improved along with glucose metabolism following the administration of glucagon-like peptide (GLP)-1 receptor agonists [ 10 , 11 ]. These results suggest that GLP-1 receptor agonists have neuroprotective effects under diabetic conditions [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, these disease manifestations improved along with glucose metabolism following the administration of glucagon-like peptide (GLP)-1 receptor agonists [ 10 , 11 ]. These results suggest that GLP-1 receptor agonists have neuroprotective effects under diabetic conditions [ 10 , 11 ]. Diabetes-related microglial dysfunction is reportedly implicated in the cognitive impairment of patients with T2DM [ 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Taxifolin Suppresses Inflammatory Responses of High-Glucose-Stimulated Mouse Microglia by Attenuating the TXNIP–NLRP3 Axis

et al. 2023

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Type 2 diabetes mellitus is associated with an increased risk of dementia, potentially through multifactorial pathologies, including neuroinflammation. Therefore, there is a need to identify novel agents that can suppress neuroinflammation and prevent cognitive impairment in diabetes. In the present study, we demonstrated that a high-glucose (HG) environment elevates the intracellular reactive oxygen species (ROS) levels and triggers inflammatory responses in the mouse microglial cell line BV-2. We further found that thioredoxin-interacting protein (TXNIP), a ROS-responsive positive regulator of the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, was also upregulated, followed by NLRP3 inflammasome activation and subsequent interleukin-1beta (IL-1β) production in these cells. Conversely, caspase-1 was not significantly activated, suggesting the involvement of noncanonical pathways in these inflammatory responses. Moreover, our results demonstrated that taxifolin, a natural flavonoid with antioxidant and radical scavenging activities, suppressed IL-1β production by reducing the intracellular ROS levels and inhibiting the activation of the TXNIP–NLRP3 axis. These findings suggest the novel anti-inflammatory effects of taxifolin on microglia in an HG environment, which could help develop novel strategies for suppressing neuroinflammation in diabetes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Taxifolin Suppresses Inflammatory Responses of High-Glucose-Stimulated Mouse Microglia by Attenuating the TXNIP–NLRP3 Axis

et al. 2023

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“…GLP-1 has ability to influence number of circulating T-killers and modulate secretion of monocytes, which reduces autoimmune damage to pancreatic islets in diabetes. In mice receiving exenatide for type 2 diabetes, a decrease in body weight and blood glucose levels was observed, along with reduced local motor activity and stress levels [36].…”

Section: «Art Of Medicine»mentioning

confidence: 98%

Morphofunctional State of Pancreas in Rats With Diabetes Mellitus

Ivantsiv,

Fedorak,

Bilinskyi

et al. 2024

Scientific and practical journal

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Goal. To analyze the literature sources concerning morphofunctional state of a pancreas in case of diabetes mellitus and treatment in white laboratory rats. Materials and methods. Generalisation of ukrainian and foreign literature data, results of meta-analyses and randomized studies. Results. Characteristics of main mechanisms of diabetes mellitus modeling was conducted in experimental animals. Literature data regarding the peculiarities of pancreatic islets in normal conditions, in case of diabetes mellitus and pharmacological correction of this disease were intensified. Anatomically, pancreas is divided into three regions: duodenal, gastric and splenic. This division in rats is somewhat conditional due to small size of organ. In some cases, highest concentration of endocrine islets is found in splenic region of gland. Islets are formed by endocrinocytes. There are four types of endocrine cells in rats: insulinocytes, glucagonocytes, somatostatinocytes and pancreatic polypeptide cells. In rats with diabetes, morphofunctional state of pancreas worsens. Numbers of insulinocytes and area of islets are decreases, level of glucose and glycosylated hemoglobin increases. Review of literature sources shows social significance of conducted research, as experimental diabetes mellitus creates discomfort and reduces the quality and lifespan of experimental animals. Prolonged uncorrected hyperglycemia creates the background for micro- and macroangiopathies development. Pharmacotherapy for diabetes primarily aims to achieve normoglycemia through dietary correction in combination with pharmacological agents. This not only slows down the progression of diabetic micro- and macroangiopathies but also extends the lives of rats. In context of absolute insulin deficiency, a priority for correcting streptozotocin-induced diabetes remains using of insulin therapy with exogenous insulin drugs and enhancing reparative processes in the gland due to improved regeneration of endocrinocytes. The priority task for scientists still remains the development of medicines capable of promoting regeneration processes of islets. According to literature sources, polytherapy of diabetes mellitus using pharmacological antidiabetic drugs can be more effective as compared to monotherapy. Several authors have studied the combined effect of insulin and exenatide (an incretin mimetic), finding that exenatide enhances the regenerative capabilities of pancreatic islets in diabetes mellitus. However, the use of incretin mimetics in type І diabetes mellitus remains controversial and requires further study. Expediency of experimental diabetes mellitus modeling is based on developing new methods for type І diabetes mellitus correction. This will promote prolonged functioning of endocrine cells, enhance regeneratory and compensatory processes in pancreas and optimize the therapeutic effect of antidiabetic drugs in experiment. Conclusion. The presented data establish the peculiarities of morphological changes in pancreatic islets in pathogenesis of diabetes, confirm the necessity of pharmacological correction of streptozotocine-induced diabetes in experimental animals by normalizing carbohydrate metabolism, activating compensatory-recovery processes and regenerations of islets with the help of nutrition and treatment. Comprehensive polytherapy and normalization of nutrition allow for the slowing of the development of diabetic micro- and macroangiopathies and cardiovascular events in the context of diabetes.

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Progress in the Pathogenesis of Diabetic Encephalopathy: The Key Role of Neuroinflammation

Luo,

Zhu,

et al. 2024

Diabetes Metabolism Res

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Diabetic encephalopathy (DE) is a severe complication that occurs in the central nervous system (CNS) and leads to cognitive impairment. DE involves various pathophysiological processes, and its pathogenesis is still unclear. This review summarised current research on the pathogenesis of diabetic encephalopathy, which involves neuroinflammation, oxidative stress, iron homoeostasis, blood‐brain barrier disruption, altered gut microbiota, insulin resistance, etc. Among these pathological mechanisms, neuroinflammation has been focused on. This paper summarises some of the molecular mechanisms involved in neuroinflammation, including the Mammalian Target of Rapamycin (mTOR), Lipocalin‐2 (LCN‐2), Pyroptosis, Advanced Glycosylation End Products (AGEs), and some common pro‐inflammatory factors. In addition, we discuss recent advances in the study of potential therapeutic targets for the treatment of DE against neuroinflammation. The current research on the pathogenesis of DE is progressing slowly, and more research is needed in the future. Further study of neuroinflammation as a mechanism is conducive to the discovery of more effective treatments for DE in the future.

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The GLP-1 receptor agonist exenatide ameliorates neuroinflammation, locomotor activity, and anxiety-like behavior in mice with diet-induced obesity through the modulation of microglial M2 polarization and downregulation of SR-A4

Cited by 10 publications

References 61 publications

Taxifolin Suppresses Inflammatory Responses of High-Glucose-Stimulated Mouse Microglia by Attenuating the TXNIP–NLRP3 Axis

Taxifolin Suppresses Inflammatory Responses of High-Glucose-Stimulated Mouse Microglia by Attenuating the TXNIP–NLRP3 Axis

Morphofunctional State of Pancreas in Rats With Diabetes Mellitus

Progress in the Pathogenesis of Diabetic Encephalopathy: The Key Role of Neuroinflammation

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