scholarly journals Therapeutic effects of liraglutide, a glucagon-like peptide-1 analog, in diabetic WBN/Kob-Leprfa rats with obesity and chronic pancreatitis

2016 ◽  
Vol 2 (5) ◽  
Author(s):  
Dai Nagakubo ◽  
Mitsuyuki Shirai ◽  
Kaoru Wakabayashi ◽  
Yuki Nakamura ◽  
Noriyuki Kaji ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Therapeutic Effects ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

CCR2 knockout exacerbates cerulein-induced chronic pancreatitis with hyperglycemia via decreased GLP-1 receptor expression and insulin secretion

2013 ◽  
Vol 304 (8) ◽  
pp. G700-G707 ◽  
Author(s):  
Yuji Nakamura ◽  
Takanori Kanai ◽  
Keita Saeki ◽  
Miho Takabe ◽  
Junichiro Irie ◽  
...  
Keyword(s):  
Cell Migration ◽  
Insulin Secretion ◽  
Chronic Pancreatitis ◽  
Immune Cells ◽  
Receptor Expression ◽  
Wild Type ◽  
Multiple Series ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Relationship

Glucagon-like peptide-1 (GLP-1) promotes insulin release; however, the relationship between the GLP-1 signal and chronic pancreatitis is not well understood. Here we focus on chemokine (C-C motif) ligand 2 (CCL2) and its receptor (CCR2) axis, which regulates various immune cells, including macrophages, to clarify the mechanism of GLP-1-mediated insulin secretion in chronic pancreatitis in mice. One and multiple series of repetitive cerulein administrations were used to induce acute and chronic cerulein pancreatitis, respectively. Acute cerulein-administered CCR2-knockout (KO) mice showed suppressed infiltration of CD11b+Gr-1low macrophages and pancreatic inflammation and significantly upregulated insulin secretion compared with paired wild-type (WT) mice. However, chronic cerulein-administered CCR2-KO mice showed significantly increased infiltration of CD11b+/Gr-1− and CD11b+/Gr-1high cells, but not CD11b+/Gr-1low cells, in pancreas with severe inflammation and significantly decreased insulin secretion compared with their WT counterparts. Furthermore, although serum GLP-1 levels in chronic cerulein-administered WT and CCR2-KO mice were comparably upregulated after cerulein administrations, GLP-1 receptor levels in pancreases of chronic cerulein-administered CCR2-KO mice were significantly lower than in paired WT mice. Nevertheless, a significantly higher hyperglycemia level in chronic cerulein-administered CCR2-KO mice was markedly restored by treatment with a GLP-1 analog to a level comparable to the paired WT mice. Collectively, the CCR2/CCL2 axis-mediated CD11b+-cell migration to the pancreas is critically involved in chronic pancreatitis-mediated hyperglycemia through the modulation of GLP-1 receptor expression and insulin secretion.

Glucagon Like Peptide-1 Receptor Agonists Alters Pancreatic and Hepatic Histology and Regulation of Endoplasmic Reticulum Stress in High-fat Diet Mouse Model

2020 ◽  
Author(s):  
Taiyong Fang ◽  
Siying Huang ◽  
Yongpeng Chen ◽  
Zongchi Chen ◽  
Jiangmu Chen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Mouse Model ◽  
Er Stress ◽  
High Fat Diet ◽  
Stress Proteins ◽  
Therapeutic Effects ◽  
High Fat ◽  
Major Health Problem ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Background Obesity is a major health problem worldwide, and non-alcoholic fatty pancreas disease (NAFPD) and non-alcoholic fatty liver disease (NAFLD) are obesity-associated complications. Liraglutide, a glucagon-like peptide-1 (GLP-1) agonist, has been approved for treatment of obesity. We aimed to evaluate the therapeutic effects of liraglutide on the complications through its regulation of endoplasmic reticulum (ER) stress. Methods A high-fat diet mouse model was established in C57BL/6J mice. Two groups of mice were fed a high-fat diet with 60% fat for 16 weeks and control mice were fed standard chow. A four-week 0.6 mg/kg/day liraglutide treatment was started in one high-fat diet group after 12 weeks of the high-fat diet. After sacrificing the mice, pancreatic and hepatic tissues were prepared for western blot and immunohistochemistry for ER stress proteins, including activating transcription factor 4 (ATF4), caspase 12, C/EBP homologous protein (CHOP) eukaryotic initiation factor 2 α (eIF2α), glucose regulated protein (GRP) 78 and protein kinase RNA-like endoplasmic reticulum kinase (PERK). Results Liraglutide significantly decreased body weight gained by mice consuming a high-fat diet (27.6 g vs. 34.5 g, P<0.001), and levels of all ER proteins increased significantly in both the pancreas and liver (all P<0.05). Expression of most ER stress proteins in pancreatic tissue correlated with disease scores of NAFLD (all P<0.05). However, no significant differences were found in pancreatic ATF 4 expression between mice without NAFLD, and those with early non-alcoholic steatohepatitis (NASH) and fibrotic NASH (P=0.122). Conclusion Liraglutide reduces the severity of NAFPD and NAFLD may through regulating the ER stress pathway and downstream apoptosis signaling.

scholarly journals Antioxidative Potentials of Incretin-Based Medications: A Review of Molecular Mechanisms

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Habib Yaribeygi ◽  
Mina Maleki ◽  
Thozhukat Sathyapalan ◽  
Tannaz Jamialahmadi ◽  
Amirhossein Sahebkar
Keyword(s):  
Oxidative Stress ◽  
Diabetic Complications ◽  
Molecular Mechanisms ◽  
Metabolic Effects ◽  
Therapeutic Effects ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Pharmacologic Agents

Glucagon-like peptide 1 receptor agonists and dipeptidyl-peptidase 4 inhibitors are medications used for managing diabetes, mimicking the metabolic effects of incretin hormones. Recent evidence suggests that these medications have antioxidative potentials in the diabetic milieu. The pathophysiology of most diabetic complications involves oxidative stress. Therefore, if incretin-based antidiabetic medications can alleviate the free radicals involved in oxidative stress, they can potentially provide further therapeutic effects against diabetic complications. However, the molecular mechanisms by which these medications protect against oxidative stress are not fully understood. In the current review, we discuss the potential molecular mechanisms behind these pharmacologic agents’ antioxidative properties.

Effects of glucagon-like peptide-1 (GLP-1) on gastric accommodation, emptying and satiety in humans

2001 ◽  
Vol 120 (5) ◽  
pp. A74-A74
Author(s):  
S AROS ◽  
D KIM ◽  
D BURTON ◽  
G THOMFORDE ◽  
A VELLA ◽  
...  
Keyword(s):  
Gastric Accommodation ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1
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