Exenatide enhances INS-1 rat pancreatic β-cell mass by increasing the protein levels of adiponectin and reducing the levels of C-reactive protein

Quan, Huibiao; Gao, Yongyi; Zhang, Huachuan; Fang, Tuanyu; Chen, Daoxiong; Lv, Zhaohui; Chen, Yanming

doi:10.3892/mmr.2014.2538

Cited by 4 publications

(2 citation statements)

References 27 publications

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“…Beyond the control of glucose and improvement of weight, multiple mechanistic studies in animals suggest that GLP-1 receptor agonism has additional positive effects including increased pancreatic beta cell mass [ 20 ], aortic vasodilation [ 21 ], cardiac protection against ischemia or reperfusion injury [ 22 ], and protection against hepatic lipid accumulation [ 23 ]. While the relevance of these findings in humans is unknown, improvements in CV risk markers (excluding DBP) and liver enzymes from baseline were observed with exenatide once weekly in the majority of body weight loss quartiles and with the greatest improvement in the quartile with the greatest reduction of body weight.…”

Section: Discussionmentioning

confidence: 99%

Association among weight change, glycemic control, and markers of cardiovascular risk with exenatide once weekly: a pooled analysis of patients with type 2 diabetes

Blonde

Pencek

MacConell

2015

Cardiovasc Diabetol

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BackgroundOverweight or obesity contributes to the development of type 2 diabetes mellitus (T2DM) and increases cardiovascular risk. Exenatide, a glucagon-like peptide-1 receptor agonist, significantly reduces glycated hemoglobin (A1C) and body weight and improves cardiovascular risk markers in patients with T2DM. As weight loss alone has been shown to reduce A1C and cardiovascular risk markers, this analysis explored whether weight loss contributed importantly to clinical responses to exenatide once weekly.MethodsA pooled analysis from eight studies of exenatide once weekly was conducted. Patients were distributed into quartiles from greatest weight loss (Quartile 1) to least loss or gain (Quartile 4). Parameters evaluated for each quartile included A1C, fasting plasma glucose (FPG), blood pressure (BP), heart rate, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, and the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST).ResultsThe median changes from baseline in body weight in Quartiles 1–4 were −6.0, –3.0, −1.0, and +1.0 kg, respectively. All quartiles had reductions in A1C (median changes −1.6, −1.4, −1.1, and −1.2%, respectively) and FPG (−41, −40, −31, and −25 mg/dL, respectively), with the greatest decreases in Quartiles 1 and 2. Most cardiovascular risk markers (except diastolic BP) and liver enzymes improved in Quartiles 1 through 3 and were relatively unchanged in Quartile 4. Higher rates of gastrointestinal adverse events and hypoglycemia were observed in Quartile 1 compared with Quartiles 2 through 4.ConclusionsExenatide once weekly improved glycemic parameters independent of weight change, although the magnitude of improvement increased with increasing weight loss. The greatest trend of improvement in glycemic parameters, cardiovascular risk factors including systolic BP, LDL-C, total cholesterol, and triglycerides, and in liver enzymes, was seen in the patient quartiles with the greatest reductions in body weight.

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Section: Discussionmentioning

confidence: 99%

Association among weight change, glycemic control, and markers of cardiovascular risk with exenatide once weekly: a pooled analysis of patients with type 2 diabetes

Blonde

Pencek

MacConell

2015

Cardiovasc Diabetol

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“…The improving effect of exenatide on β cell viability was previously demonstrated. , However, an expected synergistic effect of LLKKK18 and exenatide on the final nanoformulation with 4 μM LLKKK18 was not observed. At this concentration, the free peptide also did not have a positive effect on cell viability, suggesting that the peptide release from NPs may have been faster and that all of the peptide was released during the assay.…”

Section: Resultsmentioning

confidence: 99%

Targeting β Cells with Cathelicidin Nanomedicines Improves Insulin Function and Pancreas Regeneration in Type 1 Diabetic Rats

Cristelo,

Nunes,

Pinto

et al. 2023

ACS Pharmacol. Transl. Sci.

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Type 1 diabetes (T1D) is an incurable condition with an increasing incidence worldwide, in which the hallmark is the autoimmune destruction of pancreatic insulin-producing β cells. Cathelicidin-based peptides have been shown to improve β cell function and neogenesis and may thus be relevant while developing T1D therapeutics. In this work, a cathelicidin-derived peptide, LLKKK18, was loaded in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), surface-functionalized with exenatide toward a GLP-1 receptor, aiming the β cell-targeted delivery of the peptide. The NPs present a mean size of around 100 nm and showed long-term stability, narrow size distribution, and negative ζ-potential (−10 mV). The LLKKK18 association efficiency and loading were 62 and 2.9%, respectively, presenting slow and sustained in vitro release under simulated physiologic fluids. Glucose-stimulated insulin release in the INS-1E cell line was observed in the presence of the peptide. In addition, NPs showed a strong association with β cells from isolated rat islets. After administration to diabetic rats, NPs induced a significant reduction of the hyperglycemic state, an improvement in the pancreatic insulin content, and glucose tolerance. Also remarkable, a considerable increase in the β cell mass in the pancreas was observed. Overall, this novel and versatile nanomedicine showed glucoregulatory ability and can pave the way for the development of a new generation of therapeutic approaches for T1D treatment.

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Incretin treatment and atherosclerotic plaque stability: Role of adiponectin/APPL1 signaling pathway

Barbieri

Marfella

Esposito

et al. 2017

Journal of Diabetes and its Complications

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Exenatide enhances INS-1 rat pancreatic β-cell mass by increasing the protein levels of adiponectin and reducing the levels of C-reactive protein

Cited by 4 publications

References 27 publications

Association among weight change, glycemic control, and markers of cardiovascular risk with exenatide once weekly: a pooled analysis of patients with type 2 diabetes

Association among weight change, glycemic control, and markers of cardiovascular risk with exenatide once weekly: a pooled analysis of patients with type 2 diabetes

Targeting β Cells with Cathelicidin Nanomedicines Improves Insulin Function and Pancreas Regeneration in Type 1 Diabetic Rats

Incretin treatment and atherosclerotic plaque stability: Role of adiponectin/APPL1 signaling pathway

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