Anti-Diabetic Drugs GLP-1 Agonists and DPP-4 Inhibitors may Represent Potential Therapeutic Approaches for COVID-19

2021 ◽  
Vol 21 ◽  
Author(s):  
Aliah Alshanwani ◽  
Tarek Kashour ◽  
Amira Badr
Keyword(s):  
Adjunctive Therapy ◽  
Human Life ◽  
Significant Loss ◽  
Vascular Endothelial ◽  
Therapeutic Approaches ◽  
Protective Properties ◽  
Obesity And Diabetes ◽  
Antithrombotic Effects ◽  
Glucagon Like Peptide 1 ◽  
Dipeptidylpeptidase 4

: The fast spread of coronavirus 2019 (COVID-19) calls for immediate action to counter the associated significant loss of human life and deep economic impact. Certain patient populations like those with obesity and diabetes are at higher risk for acquiring severe COVID-19 disease and have a higher risk of COVID-19 associated mortality. In the absence of an effective and safe vaccine, the only immediate promising approach is to repurpose an existing approved drug. Several drugs have been proposed and tested as adjunctive therapy for COVID-19. Among these drugs are the glucagon-like peptide-1 (GLP-1) 2 agonists and the dipeptidylpeptidase-4 (DPP-4) inhibitors. Beyond their glucose-lowering effects, these drugs have several pleiotropic protective properties, which include cardioprotective effects, anti-inflammatory and immunomodulatory activities, antifibrotic effects, antithrombotic effects, and vascular endothelial protective properties. This narrative review discusses these protective properties and addresses their scientific plausibility for their potential use as adjunctive therapy for COVID-19 disease.

Activation of GLP-1 and Glucagon Receptors Regulates Bile Homeostasis Independent of Thyroid Hormone

2019 ◽  
Vol 12 (2) ◽  
pp. 139-146
Author(s):  
Vishal J. Patel ◽  
Amit A. Joharapurkar ◽  
Samadhan G. Kshirsagar ◽  
Brijesh K. Sutariya ◽  
Maulik S. Patel ◽  
...  
Keyword(s):  
Single Dose ◽  
Lipid Metabolism ◽  
Thyroid Hormone ◽  
Fibroblast Growth Factor 21 ◽  
Dose Treatment ◽  
Obesity And Diabetes ◽  
Serum T3 ◽  
Serum T4 ◽  
Glucagon Like Peptide 1 ◽  
Glucagon Receptors

Background: Balanced coagonists of glucagon-like peptide-1 (GLP-1) and glucagon receptors are emerging therapies for the treatment of obesity and diabetes. Such coagonists also regulate lipid metabolism, independent of their body weight lowering effects. Many actions of the coagonists are partly mediated by fibroblast growth factor 21 (FGF21) signaling, with the major exception of bile homeostasis. Since thyroid hormone is an important regulator of bile homeostasis, we studied the involvement of thyroid hormone in coagonist-induced changes in lipid and bile metabolism. Methods: We evaluated the effect of a single dose of coagonist Aib2 C24 chimera2 at 150 to 10000 µg/kg on tetraiodothyronine (T4) and triiodothyronine (T3) in high-fat diet-induced obese (DIO) mice and chow-fed mice. Repeated dose treatment of coagonist (150 µg/kg, subcutaneously) was assessed in four mice models namely, on lipid and bile homeostasis in DIO mice, propylthiouracil (PTU)-treated DIO mice, methimazole (MTM)-treated DIO mice and choline-deficient, L-amino acid-defined, highfat diet (CDAHFD)-induced nonalcoholic steatohepatitis (NASH). Results: Single dose treatment of coagonist did not alter serum T3 and T4 in chow-fed mice and DIO mice. Coagonist treatment improved lipid metabolism and biliary cholesterol excretion. Chronic treatment of GLP-1 and glucagon coagonist did not alter serum T3 in hypothyroid DIO mice and CDAHFDinduced NASH. Coagonist increased serum T4 in DIO mice after 4 and 40 weeks of treatment, though no change in T4 levels was observed in hypothyroid mice or mice with NASH. Conclusion: Our data demonstrate that coagonist of GLP-1 and glucagon receptors does not modulate bile homeostasis via thyroid signaling.

Let-7e-5p Regulates GLP-1 Content and Basal Release From Enteroendocrine L Cells From DIO Male Mice

Endocrinology ◽  
2019 ◽  
Vol 161 (2) ◽  
Author(s):  
Sandra Handgraaf ◽  
Rodolphe Dusaulcy ◽  
Florian Visentin ◽  
Jacques Philippe ◽  
Yvan Gosmain
Keyword(s):  
Compensatory Mechanism ◽  
L Cells ◽  
Low Fat Diet ◽  
Obesity And Diabetes ◽  
Basal Release ◽  
Glucagon Like Peptide 1 ◽  
Cell Transcriptome ◽  
Microarray Analyses

Abstract Characterization of enteroendocrine L cells in diabetes is critical for better understanding of the role of glucagon-like peptide-1 (GLP-1) in physiology and diabetes. We studied L-cell transcriptome changes including microRNA (miRNA) dysregulation in obesity and diabetes. We evaluated the regulation of miRNAs through microarray analyses on sorted enteroendocrine L cells from control and obese glucose-intolerant (I-HFD) and hyperglycemic (H-HFD) mice after 16 weeks of respectively low-fat diet (LFD) or high-fat diet (HFD) feeding. The identified altered miRNAs were studied in vitro using the mouse GLUTag cell line to investigate their regulation and potential biological functions. We identified that let-7e-5p, miR-126a-3p, and miR-125a-5p were differentially regulated in L cells of obese HFD mice compared with control LFD mice. While downregulation of let-7e-5p expression was observed in both I-HFD and H-HFD mice, levels of miR-126a-3p increased and of miR-125a-5p decreased significantly only in I-HFD mice compared with controls. Using miRNA inhibitors and mimics we observed that modulation of let-7e-5p expression affected specifically GLP-1 cellular content and basal release, whereas Gcg gene expression and acute GLP-1 secretion and cell proliferation were not affected. In addition, palmitate treatment resulted in a decrease of let-7e-5p expression along with an increase in GLP-1 content and release, suggesting that palmitate acts on GLP-1 through let-7e-5p. By contrast, modulation of miR-125a-5p and miR-126a-3p in the same conditions did not affect content or secretion of GLP-1. We conclude that decrease of let-7e-5p expression in response to palmitate may constitute a compensatory mechanism contributing to maintaining constant glycemia in obese mice.

scholarly journals Neuronal guidance proteins in cardiovascular inflammation

2021 ◽  
Vol 116 (1) ◽  
Author(s):  
Marius Keller ◽  
Valbona Mirakaj ◽  
Michael Koeppen ◽  
Peter Rosenberger
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Vascular Endothelial ◽  
Therapeutic Approaches ◽  
Immune Cell Activation ◽  
Cytokines And Chemokines ◽  
The Future ◽  
Cardiovascular Pathologies ◽  
Neuronal Guidance

AbstractCardiovascular pathologies are often induced by inflammation. The associated changes in the inflammatory response influence vascular endothelial biology; they complicate the extent of ischaemia and reperfusion injury, direct the migration of immune competent cells and activate platelets. The initiation and progression of inflammation is regulated by the classical paradigm through the system of cytokines and chemokines. Therapeutic approaches have previously used this knowledge to control the extent of cardiovascular changes with varying degrees of success. Neuronal guidance proteins (NGPs) have emerged in recent years and have been shown to be significantly involved in the control of tissue inflammation and the mechanisms of immune cell activation. Therefore, proteins of this class might be used in the future as targets to control the extent of inflammation in the cardiovascular system. In this review, we describe the role of NGPs during cardiovascular inflammation and highlight potential therapeutic options that could be explored in the future.

Liraglutide for psychiatric disorders: clinical evidence and challenges

2018 ◽  
Vol 36 (2) ◽  
Author(s):  
Mehmet Akif Camkurt ◽  
Luca Lavagnino ◽  
Xiang Y. Zhang ◽  
Antonio L Teixeira
Keyword(s):  
Risk Factors ◽  
Psychiatric Disorders ◽  
Clinical Evidence ◽  
Preclinical Studies ◽  
Potential Candidate ◽  
Obesity And Diabetes ◽  
Treatment Of Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Diabetes And Obesity

Abstract Obesity and diabetes are both risk factors and consequences of psychiatric disorders. Glucagon like peptide 1 (GLP-1) receptor agonists such as liraglutide are widely used in the treatment of diabetes and obesity. There are considerable amounts of preclinical studies showing the effects of liraglutide on promotion of neurogenesis, while preventing apoptosis and oxidation. Preliminary clinical evidence has suggested that liraglutide could decrease weight gain, improve cognition and prevent cognitive decline. Accordingly, liraglutide has been regarded as a potential candidate for the management of psychiatric disorders. Herein, we will discuss the association between obesity/diabetes and psychiatric disorders, and the emerging use of liraglutide in psychiatry.

The gut and cardiovascular diseases

ESC CardioMed ◽  
2018 ◽  
pp. 1090-1093
Author(s):  
Giuseppe Rosano
Keyword(s):  
Heart Failure ◽  
Cardiovascular Diseases ◽  
Gut Microbiome ◽  
Intestinal Barrier ◽  
Therapeutic Approaches ◽  
Barrier Permeability ◽  
New Therapeutic Approaches ◽  
Obesity And Diabetes ◽  
Gut Homeostasis ◽  
Progression Of Atherosclerosis

The physiological functioning of the gut is central for the pharmacokinetics of orally administered cardiovascular drugs and alteration of the gut homeostasis may have relevant repercussions on the effect of these drugs. The gut microbiome may affect the absorption and metabolism of nutrients favouring the development of obesity and diabetes. Furthermore, alterations in intestinal barrier permeability lead to the penetration of bacteria and bacterial wall products into the circulation and may contribute to the progression of atherosclerosis and worsening of heart failure. Despite the suggestions of the possible interaction between the gut and the cardiovascular system and of stimulating novel mechanisms for disease progression that may open to new therapeutic approaches, the available evidence must be considered preliminary.

scholarly journals Essential Role for Sphingosine Kinases in Neural and Vascular Development

2005 ◽  
Vol 25 (24) ◽  
pp. 11113-11121 ◽  
Author(s):  
Kiyomi Mizugishi ◽  
Tadashi Yamashita ◽  
Ana Olivera ◽  
Georgina F. Miller ◽  
Sarah Spiegel ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Vascular Development ◽  
Neural Tube Closure ◽  
Vascular Endothelial ◽  
Therapeutic Approaches ◽  
Cellular Processes ◽  
Survival Pathway ◽  
Sphingosine 1 Phosphate ◽  
Sphingosine Kinases ◽  
Endothelial Growth Factor

ABSTRACT Sphingosine-1-phosphate (S1P), an important sphingolipid metabolite, regulates diverse cellular processes, including cell survival, growth, and differentiation. Here we show that S1P signaling is critical for neural and vascular development. Sphingosine kinase-null mice exhibited a deficiency of S1P which severely disturbed neurogenesis, including neural tube closure, and angiogenesis and caused embryonic lethality. A dramatic increase in apoptosis and a decrease in mitosis were seen in the developing nervous system. S1P1 receptor-null mice also showed severe defects in neurogenesis, indicating that the mechanism by which S1P promotes neurogenesis is, in part, signaling from the S1P1 receptor. Thus, S1P joins a growing list of signaling molecules, such as vascular endothelial growth factor, which regulate the functionally intertwined pathways of angiogenesis and neurogenesis. Our findings also suggest that exploitation of this potent neuronal survival pathway could lead to the development of novel therapeutic approaches for neurological diseases.

scholarly journals Multiagonist Unimolecular Peptides for Obesity and Type 2 Diabetes: Current Advances and Future Directions

2020 ◽  
Vol 13 ◽  
pp. 117955142090584 ◽  
Author(s):  
Annie Hasib
Keyword(s):  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Hormone Receptors ◽  
Gut Hormones ◽  
Metabolic Effects ◽  
Therapeutic Approaches ◽  
Obesity And Diabetes ◽  
Gut Hormone ◽  
Prevalence Of Obesity

The ever-increasing prevalence of obesity and Type 2 diabetes has necessitated the development of newer and more effective approaches for achieving efficient glycemic control and weight loss. Conventional treatment methods often result in weight gain, further deteriorating the already impaired metabolic control in people with obesity/Type 2 diabetes. Alleviation of obesity and diabetes achieved after bariatric surgeries highlight the therapeutic importance of gut-brain axis and entails development of more patient-friendly approaches replicating the positive metabolic effects of bariatric surgery. Given the potential involvement of several gut hormones in the success of bariatric surgery, the therapeutic importance of synergistic interaction between these hormones for improved metabolism cannot be ignored. Many unimolecular multiagonist peptides are in preclinical and clinical trials as they maximize the combinatorial metabolic efficacy by concurrent activation of multiple gut hormone receptors. This review summarizes the ongoing developments of multiagonist peptides as novel therapeutic approaches against obesity-diabetes.

Incretins: pathophysiological and therapeutic implications of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1

2008 ◽  
Vol 61 (4) ◽  
pp. 401-409 ◽  
Author(s):  
L R Ranganath
Keyword(s):  
B Cell ◽  
Cell Mass ◽  
Therapeutic Agents ◽  
Glycosidase Inhibitors ◽  
Therapeutic Implications ◽  
Obesity And Diabetes ◽  
Control Of Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
High Doses

Incretins such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are intestinal postprandial hormones that stimulate insulin release from the pancreas as long as circulating glucose concentrations are raised. In addition to their effect on insulin secretion and consequent glucose lowering, GIP and GLP-1, especially the latter, have a number of physiological effects such as inhibition of glucagon release, gastric emptying and food intake, as well as a tropic action on pancreatic B-cell mass. There is currently a pandemic of obesity and diabetes, and existing treatments are largely inadequate both in regard to efficacy as well as their ability to tackle important factors in the pathogenesis of type 2 diabetes (T2D). There is increasing evidence that current treatments do not address the issue of progressive B-cell failure in T2D. Since obesity is the engine that is driving the epidemic of diabetes, it is disappointing that most treatments that succeed in lowering plasma glucose are also associated with weight gain. It is now well established that intensively treated T2D has a better outcome than standard treatment. Consequently, achieving better control of diabetes with lower HbA1c is the goal of optimal treatment. Despite the use of usual therapeutic agents in T2D, often in high doses and as combinations, such as metformin, sulphonylurea, α-glycosidase inhibitors, thiazolidinediones and a number of animal and human insulin preparations, optimal control of glycaemia is not achieved. The use of incretins as therapeutic agents offers a new approach to the treatment of T2D.

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