Glucagon and glucagon-like peptide-1 as novel anti-inflammatory and immunomodulatory compounds

Insuela, Daniella Bianchi Reis; Carvalho, Vinícius F.

doi:10.1016/j.ejphar.2017.07.015

Cited by 51 publications

(36 citation statements)

References 106 publications

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“…Furthermore an inflammatory status, as seen in pathologies such as type 2 diabetes, might compromise the gut mucosal permeability, leading to the exposure of intestinal EECs to luminal LPS, and a TLR4-mediated release of GLP-1 ( 229 ). This is consistent with the knowledge that GLP-1, as well as glucagon, has shown to possess powerful anti-inflammatory properties in vivo , an area that hold with vast therapeutical potential ( 136 , 230 ).…”

Section: Expanding the Physiology Of Glp-1supporting

confidence: 90%

“…GLP-1 stimulates the β-cells to produce Insulin, blocks pancreatic α-cells' glucagon release via somatostatin ( 96 ), slows down gastric emptying ( 131 ), improves peripheral glucose tolerance ( 132 ), suppresses appetite in the hypothalamus and amygdala ( 97 ), increases β-cell mass, GSIS, and elicits protection from glucolipotoxicity ( 133 ) and apoptosis ( 134 ). Curiously, it also regulates bone physiology ( 135 ), and shows anti-inflammatory properties ( 136 ).…”

Section: The Physiology Of Glp-1mentioning

confidence: 99%

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Dissecting the Physiology and Pathophysiology of Glucagon-Like Peptide-1

Paternoster

Falasca

2018

Front. Endocrinol.

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An aging world population exposed to a sedentary life style is currently plagued by chronic metabolic diseases, such as type-2 diabetes, that are spreading worldwide at an unprecedented rate. One of the most promising pharmacological approaches for the management of type 2 diabetes takes advantage of the peptide hormone glucagon-like peptide-1 (GLP-1) under the form of protease resistant mimetics, and DPP-IV inhibitors. Despite the improved quality of life, long-term treatments with these new classes of drugs are riddled with serious and life-threatening side-effects, with no overall cure of the disease. New evidence is shedding more light over the complex physiology of GLP-1 in health and metabolic diseases. Herein, we discuss the most recent advancements in the biology of gut receptors known to induce the secretion of GLP-1, to bridge the multiple gaps into our understanding of its physiology and pathology.

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Section: Expanding the Physiology Of Glp-1supporting

confidence: 90%

Section: The Physiology Of Glp-1mentioning

confidence: 99%

Dissecting the Physiology and Pathophysiology of Glucagon-Like Peptide-1

Paternoster

Falasca

2018

Front. Endocrinol.

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“…Physically active individuals have lower inflammatory biomarker concentrations than their inactive counterparts,24 possibly explained by anti-inflammatory effects of an acute bout of exercise44 and lower levels of visceral adipose tissue 45. GLP-1 has also emerged as an immunomodulatory agent 46 47. In mice, GLP-1 RA administration reduces macrophage accumulation and inflammatory markers in the arterial wall,48 adipose tissue49 and heart 50.…”

Section: Introductionmentioning

confidence: 99%

Protocol for a randomised controlled trial of the combined effects of the GLP-1 receptor agonist liraglutide and exercise on maintenance of weight loss and health after a very low-calorie diet

et al. 2019

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IntroductionThe success rate of weight loss maintenance is limited. Therefore, the purpose of this study is to investigate the maintenance of weight loss and immunometabolic health outcomes after diet-induced weight loss followed by 1-year treatment with a glucagon-like peptide-1 receptor agonist (liraglutide), physical exercise or the combination of both treatments as compared with placebo in individuals with obesity.Methods and analysisThis is an investigator-initiated, randomised, placebo-controlled, parallel group trial. We will enrol expectedly 200 women and men (age 18–65 years) with obesity (body mass index 32–43 kg/m2) to adhere to a very low-calorie diet (800 kcal/day) for 8 weeks in order to lose at least 5% of body weight. Subsequently, participants will be randomised in a 1:1:1:1 ratio to one of four study groups for 52 weeks: (1) placebo, (2) exercise 150 min/week+placebo, (3) liraglutide 3.0 mg/day and (4) exercise 150 min/week+liraglutide 3.0 mg/day. The primary endpoint is change in body weight from randomisation to end-of-treatment.Ethics and disseminationThe trial has been approved by the ethical committee of the Capital Region of Denmark and the Danish Medicines Agency. The trial will be conducted in agreement with the Declaration of Helsinki and monitored to follow the guidelines for good clinical practice. Results will be submitted for publication in international peer-reviewed scientific journals.Trial registration number2015-005585-32

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“…To further evaluate this, future experiments should test the effect of GLP hormones in premature RE and under challenge conditions. The latter acknowledges that both GLP-1 and GLP-2 display their beneficial effects on intestinal epithelia most prominently under stress conditions like inflammation (Insuela & Carvalho, 2017;Nakame, Kaji, Mukai, Shinyama, & Matsufuji, 2016) and feed restriction (Kvidera et al, 2017;Sigalet et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Effects of glucagon‐like peptides 1 and 2 and epidermal growth factor on the epithelial barrier of the rumen of adult sheep

Greco

Amasheh

Shen

et al. 2019

Animal Physiology Nutrition

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Epidermal growth factor (EGF) and glucagon‐like peptides (GLP) modulate the tight junctions (TJ) of the intestinal epithelial barrier (EB) of monogastric animals. This work tried to elucidate whether GLP‐1, GLP‐2 and EGF can affect the EB of the rumen. Ovine ruminal epithelia were incubated in Ussing chambers for 7 hr with 25 or 250 nM of either GLP‐1 or GLP‐2 on the serosal side, with 2.5 nM of EGF on the serosal side or with 0.25 or 2.5 nM EGF on the mucosal side. No treatment affected tissue conductance. Short‐circuit current (Isc) was affected by time and treatment and their interactions. Only 250 nM of either GLP‐1 or GLP‐2 decreased Isc in certain periods compared with 25 nM GLP‐1 or 0.25 nM mucosally applied EGF; however, not when compared to control epithelia. Fluorescein flux rates (Jfluor) of ruminal epithelia were affected by treatment, time and time × treatment interaction. The time × treatment interaction was based on an increase in Jfluor between the first and last hour in epithelia incubated with 25 nM GLP‐1 or GLP‐2 and in epithelia incubated with EGF. After 7 hr incubation, claudin‐7 mRNA expression was downregulated in all treatments. Claudin‐1 mRNA was upregulated after incubation with 2.5 nM EGF on the serosal side, claudin‐4 mRNA was downregulated by 2.5 nM EGF on the mucosal side, and occludin mRNA was increased after incubation with 250 nM GLP‐2. The protein abundance of all tested TJ proteins was not influenced by treatment. We conclude that GLP‐1, GLP‐2, and EGF have no obvious acute effects on the EB of ruminal epithelia under simulated physiological conditions ex vivo. However, by decreasing the mRNA expression of claudin‐7 and partly affecting other TJ proteins, they may modulate EB in the longer term or under certain conditions.

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Glucagon and glucagon-like peptide-1 as novel anti-inflammatory and immunomodulatory compounds

Cited by 51 publications

References 106 publications

Dissecting the Physiology and Pathophysiology of Glucagon-Like Peptide-1

Dissecting the Physiology and Pathophysiology of Glucagon-Like Peptide-1

Protocol for a randomised controlled trial of the combined effects of the GLP-1 receptor agonist liraglutide and exercise on maintenance of weight loss and health after a very low-calorie diet

Effects of glucagon‐like peptides 1 and 2 and epidermal growth factor on the epithelial barrier of the rumen of adult sheep

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