GLP-1 receptor agonist liraglutide exerts central action to induce β-cell proliferation through medulla to vagal pathway in mice

Parmila, Kumari; Nakata, Masao; Zhang, Bo Yang; Otgon-Uul, Zesemdorj; Yada, Toshihiko

doi:10.1016/j.bbrc.2018.03.199

Cited by 10 publications

(3 citation statements)

References 37 publications

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“…5 Some animal studies (primarily conducted in mice) have investigated intracerebroventricular injection of the GLP-1 RA liraglutide and native GLP-1. 14 Their findings suggest that liraglutide and endogenous GLP-1 induce pancreatic beta-cell proliferation; they also suggest that the neural pathway of beta-cell proliferation is highly sensitive to GLP-1 RAs and involves the brainstem areas equipped with leaky blood-brain barriers. Therefore, the effect of beta-cell proliferation may occur in patients with diabetes treated with GLP-1 RAs.…”

Section: Benefits Of Glp-1 Ra Therapymentioning

confidence: 99%

GLP-1 receptor agonists

Clark

2024

Jaapa

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Type 2 diabetes mellitus (T2DM) is a chronic medical condition affecting millions of individuals worldwide. The burden of disease is significant, as demonstrated by high morbidity and mortality and billions of healthcare dollars spent. The pathophysiology of T2DM is complex, with eight primary deficits. In recent years, an increased focus has been placed on incretin hormones, such as glucagon-like peptide-1 (GLP-1) for its glucose-lowering benefits. Several FDA-approved short-acting and long-acting GLP-1 receptor agonists (GLP-1 RAs) are available in the United States for the treatment of T2DM. These are liraglutide, exenatide, dulaglutide, and semaglutide, all administered via subcutaneous injection. Semaglutide is also available in an oral formulation. A newer dual glucose-dependent insulinotropic peptide (GIP) and GLP-1 RA, tirzepatide, is available as a subcutaneous injectable. In addition to improving glycemic control, GLP-1 RAs have been shown to lower total body weight, BP, and cholesterol as well as to improve renal function and beta-cell proliferation. These agents should be considered in every patient with T2DM due to their substantial clinical benefits and potential to help reduce disease burden.

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Section: Benefits Of Glp-1 Ra Therapymentioning

confidence: 99%

GLP-1 receptor agonists

Clark

2024

Jaapa

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“…GLP-1RA may influence the activity of two opposite subgroup neurons within ARC, which are related to food intake and body weight, containing proopiomelanocortin/cocaine- and amphetamine-regulated transcript (POMC/CART) and neuropeptide Y/agouti related peptide (NPY/AgRP) neurons; 137 , 157 In PVN, 158 , 159 GLP-1RA particularly, has been shown to interact with neuropeptides, such as AVP, oxytocin, and CRH release, thereby regulating eating and stress; BNST, 160 , 161 which is associated with suppression of food intake and stress response; LPB, 162 which reportedly mediates food intake and reward; hippocampus, 163 which influences cognition performance for food intake in rodents; NTS, 164 a major critical knot for afferent signals of gastro-intestine and satiety; VTA 165 , 166 and NAc, 167–169 which process reward for food and drug behavior; amygdala 170 , 171 that influences glucose homeostasis and food reward; as well as HPA-axis 172 , 173 which could affect stress and SNS. 174 Previous studies have reported the comprehensive effects of GLP-1RA on the CNS, which go beyond the levels of blood glucose modulation, but are associated with numerous metabolic aspects such as food intake and preference, 127 , 175 water intake, 176 energy expenditure, 177 body weight reduction, 178 pancreatic function, 132 , 179 , 180 hypertension, 181 stress, 182 addiction behaviors, 183 , 184 as well as neurodegenerative disorders, such as Alzheimer and Parkinson diseases. 185 These metabolic effects have proved versatile central actions of GLP-1RAs, and have been associated with direct or indirect potential secondary benefits like reduced risks of dyslipidemia, anti-atherosclerosis, modulation of cardiovascular activity, and proteinuria, as well as influencing clinical outcomes in T2D patients.…”

Section: Central Nervous Pathways Associated With Glp-1ras’ Treatment Outcomesmentioning

confidence: 99%

An Overview of Similarities and Differences in Metabolic Actions and Effects of Central Nervous System Between Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) and Sodium Glucose Co-Transporter-2 Inhibitors (SGLT-2is)

Nguyen

Gong

et al. 2021

DMSO

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GLP-1 receptor agonists (GLP-1RAs) and SGLT-2 inhibitors (SGLT-2is) are novel antidiabetic medications associated with considerable cardiovascular benefits therapying treatment of diabetic patients. GLP-1 exhibits atherosclerosis resistance, whereas SGLT-2i acts to ameliorate the neuroendocrine state in the patients with chronic heart failure. Despite their distinct modes of action, both factors share pathways by regulating the central nervous system (CNS). While numerous preclinical and clinical studies have demonstrated that GLP-1 can access various nuclei associated with energy homeostasis and hedonic eating in the CNS via blood–brain barrier (BBB), research on the activity of SGLT-2is remains limited. In our previous studies, we demonstrated that both GLP-1 receptor agonists (GLP-1RAs) liraglutide and exenatide, as well as an SGLT-2i, dapagliflozin, could activate various nuclei and pathways in the CNS of Sprague Dawley (SD) rats and C57BL/6 mice, respectively. Moreover, our results revealed similarities and differences in neural pathways, which possibly regulated different metabolic effects of GLP-1RA and SGLT-2i via sympathetic and parasympathetic systems in the CNS, such as feeding, blood glucose regulation and cardiovascular activities (arterial blood pressure and heart rate control). In the present article, we extensively discuss recent preclinical studies on the effects of GLP-1RAs and SGLT-2is on the CNS actions, with the aim of providing a theoretical explanation on their mechanism of action in improvement of the macro-cardiovascular risk and reducing incidence of diabetic complications. Overall, these findings are expected to guide future drug design approaches.

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“…6 Liraglutide, in addition to controlling hyperglycemia also upsurges glucose dependent insulin secretion (GSIS) from pancreatic beta cells. 7 However high cost and parenteral administration are the two main factors which limits the use of these remarkable GLP-1 analogues. 8 Due to the risk profile of antidiabetic agents, herbal medicines in are popular in practice for treating diabetes as they are well known to be free from toxic effects.…”

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confidence: 99%

Effect Of Withania Coagulans And Liraglutide On Serum Glp-1, Postprandial And Fasting Blood Glucose In Streptozotocin Induced Diabetic Rats

Samad¹,

Rajpoot²,

Ayaz³

et al. 2019

J. Bahria Univ. Med. Dent. Coll.

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Objective: To evaluate effect of Withania coagulans and liraglutide on serum Glucagon like peptide-1, Postprandial and Fasting Blood Glucose levels in streptozotocin induced diabetic rat. Study Design and Setting: This randomize control trile was conducted at Islamic International Medical College in collaboration with National Institute of Health Islamabad. Methodology: This randomized controlled study was performed on a total of forty male Sprague dawly rats, which were initially divided into two groups; Group A (n=10) and Experimental Group (n=30). Diabetes in the Experimental group B was induced by intraperitoneal administration of streptozotocin for 5 days (30mg/kg/day). Diabetes was checked in experimental group by measuring fasting blood glucose (mg/dl) on day 6. Experimental group was further divided into Group B (Diabetic control), Group C (Withania coagulans-treated) and Group D (Liraglutide-treated). Blood sampling was done at day 30 and serum GLP-1, postprandial and fasting blood glucose levels were measured and compared in all groups. Results: Fasting and postprandial blood glucose levels of group C and D were significantly reduced as compared to group B. Serum GLP-1 levels were significantly increased in group C and D as compared to group B. Conclusion: Withania coagulans reduces hyperglycemia in diabetic rats through increasing GLP-1 hormone.

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GLP-1 receptor agonist liraglutide exerts central action to induce β-cell proliferation through medulla to vagal pathway in mice

Cited by 10 publications

References 37 publications

GLP-1 receptor agonists

GLP-1 receptor agonists

An Overview of Similarities and Differences in Metabolic Actions and Effects of Central Nervous System Between Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) and Sodium Glucose Co-Transporter-2 Inhibitors (SGLT-2is)

Effect Of Withania Coagulans And Liraglutide On Serum Glp-1, Postprandial And Fasting Blood Glucose In Streptozotocin Induced Diabetic Rats

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