GLP-1

Reed, Joshua; Kanamarlapudi, Venkateswarlu

doi:10.1007/978-3-319-67199-4_101966

Cited by 3 publications

(18 citation statements)

References 19 publications

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“… 257 , 258 Exendin-4 was originally isolated from the saliva of the Gila monster lizard and is resistant to the action of DPP-IV. 257 , 259 Key pharmacological and clinical features of clinically available GLP-1R agonists are presented in Table 3 and Figure 8 compares the amino acid sequence of native GLP-1 and the GLP-1 analogues liraglutide and exenatide.…”

Section: Pharmacological Treatments and Lifestyle Changes For T2dmentioning

confidence: 99%

“…In addition to augmenting insulin secretion from islet beta-cells, both in vivo and in vitro studies have produced evidence that GLP-1 action improves islet beta-cell survival and proliferation, 252 , 259 which is also a relevant area of research as it is well established that T2D pathology is associated with an increased rate of islet beta-cell apoptosis. 309 Given the reduced population of these cells in patients, 310 enhanced proliferation would, in theory, be desirable to increase plasma insulin levels in patients to promote normoglycaemia and normolipidaemia.…”

Section: Future Perspectivesmentioning

confidence: 99%

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A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives

Reed¹,

Bain²,

Kanamarlapudi³

2021

DMSO

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237

124

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Type 2 diabetes (T2D), which has currently become a global pandemic, is a metabolic disease largely characterised by impaired insulin secretion and action. Significant progress has been made in understanding T2D aetiology and pathogenesis, which is discussed in this review. Extrapancreatic pathology is also summarised, which demonstrates the highly multifactorial nature of T2D. Glucagon-like peptide (GLP)-1 is an incretin hormone responsible for augmenting insulin secretion from pancreatic beta-cells during the postprandial period. Given that native GLP-1 has a very short half-life, GLP-1 mimetics with a much longer half-life have been developed, which are currently an effective treatment option for T2D by enhancing insulin secretion in patients. Interestingly, there is continual emerging evidence that these therapies alleviate some of the post-diagnosis complications of T2D. Additionally, these therapies have been shown to induce weight loss in patients, suggesting they could be an alternative to bariatric surgery, a procedure associated with numerous complications. Current GLP-1-based therapies all act as orthosteric agonists for the GLP-1 receptor (GLP-1R). Interestingly, it has emerged that GLP-1R also has allosteric binding sites and agonists have been developed for these sites to test their therapeutic potential. Recent studies have also demonstrated the potential of bi- and tri-agonists, which target multiple hormonal receptors including GLP-1R, to more effectively treat T2D. Improved understanding of T2D aetiology/pathogenesis, coupled with the further elucidation of both GLP-1 activity/targets and GLP-1R mechanisms of activation via different agonists, will likely provide better insight into the therapeutic potential of GLP-1-based therapies to treat T2D.

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Section: Pharmacological Treatments and Lifestyle Changes For T2dmentioning

confidence: 99%

Section: Future Perspectivesmentioning

confidence: 99%

A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives

Reed¹,

Bain²,

Kanamarlapudi³

2021

DMSO

Self Cite

237

124

View full text Add to dashboard Cite

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“… 11 Additionally, GLP-1R activation also induces the translocation to the nucleus of the PDX-1 transcription factor, giving GLP-1 a role in islet beta-cell survival. 112 , 204 , 205 Interestingly, chronic liraglutide administration to diabetic mice that had been injected with alloxan prevented the loss of beta-cell mass, which was shown to be due to both an increase in beta-cell proliferation and a decrease in apoptosis. 206 Liraglutide treatment was also demonstrated to inhibit beta-cell apoptosis in isolated human pancreatic beta-cells, and after 24 hours, the islet beta-cell proliferation rate tripled.…”

Section: Introductionmentioning

confidence: 99%

“… 32 , 109 , 112 GLP-1 analogues effectively reduce hyperglycaemia in patients as they have a much longer half-life than native GLP-1, prolonging the incretin effect in patients. 32 , 112 The ability of GLP-1 to stimulate insulin secretion is dependent on high glucose levels, as this hormone does not induce insulin secretion in the presence of low blood glucose. 11 Additionally, GLP-1R activation also induces the translocation to the nucleus of the PDX-1 transcription factor, giving GLP-1 a role in islet beta-cell survival.…”

Section: Introductionmentioning

confidence: 99%

“…Findings from multiple studies have demonstrated that GLP-1 also regulates the immune system. 11 , 112 In rodents, GLP-1R mRNA is present in several immune cell types: macrophages, Treg cells, thymocytes, splenocytes, bone marrow-derived cells, and natural killer cells etc. 11 Administration of GLP-1R agonists to humans or animals with T2D or obesity is usually associated with a reduction in local or systemic inflammation.…”

Section: Introductionmentioning

confidence: 99%

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The Regulation of Metabolic Homeostasis by Incretins and the Metabolic Hormones Produced by Pancreatic Islets

Reed,

Bain,

Kanamarlapudi

2024

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Comparative Analysis of Orthosteric and Allosteric GLP-1R Agonists’ Effects on Insulin Secretion from Healthy, Diabetic, and Recovered INS-1E Pancreatic Beta Cells

Reed,

Higginbotham,

Bain

et al. 2024

IJMS

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Despite the availability of different treatments for type 2 diabetes (T2D), post-diagnosis complications remain prevalent; therefore, more effective treatments are desired. Glucagon-like peptide (GLP)-1-based drugs are currently used for T2D treatment. They act as orthosteric agonists for the GLP-1 receptor (GLP-1R). In this study, we analyzed in vitro how the GLP-1R orthosteric and allosteric agonists augment glucose-stimulated insulin secretion (GSIS) and intracellular cAMP production (GSICP) in INS-1E pancreatic beta cells under healthy, diabetic, and recovered states. The findings from this study suggest that allosteric agonists have a longer duration of action than orthosteric agonists. They also suggest that the GLP-1R agonists do not deplete intracellular insulin, indicating they can be a sustainable and safe treatment option for T2D. Importantly, this study demonstrates that the GLP-1R agonists variably augment GSIS through GSICP in healthy, diabetic, and recovered INS-1E cells. Furthermore, we find that INS-1E cells respond differentially to the GLP-1R agonists depending on both glucose concentration during and before treatment and/or whether the cells have been previously exposed to these drugs. In conclusion, the findings described in this manuscript will be useful in determining in vitro how pancreatic beta cells respond to T2D drug treatments in healthy, diabetic, and recovered states.

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GLP-1

Cited by 3 publications

References 19 publications

A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives

A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives

The Regulation of Metabolic Homeostasis by Incretins and the Metabolic Hormones Produced by Pancreatic Islets

Comparative Analysis of Orthosteric and Allosteric GLP-1R Agonists’ Effects on Insulin Secretion from Healthy, Diabetic, and Recovered INS-1E Pancreatic Beta Cells

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