exenatide and Pancreatic-Diseases

GLP-1 agonists have been widely used in the therapy of type 2 diabetes due to their beneficial effects regarding weight loss and low risk of hypoglycemia. However, some safety concerns have been raised in view of possible detrimental effects to the pancreas. The future place of GLP-1 agonist in diabetes therapy will be determined by the current safety evaluation and data from studies investigating long-term effects.

Topics: Blood Pressure; Diabetes Mellitus, Type 2; Exenatide; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Hypoglycemic Agents; Pancreatic Diseases; Peptides; Venoms

Hepatic ischemia/reperfusion-induced pancreatic injury (HI/RPI) is an important pathophysiological phenomenon in clinics. Exenatide is found to have hepatopancreatic protection; however, the half-life of exenatide is extremely short, which limits its clinical application. In the present study, we described an exenatide nanocarrier based on poly(L-lysine)-poly(ethylene glycol)-poly(L-lysine) (PLL-PEG-PLL) and aimed to investigate the protective effects of exenatide/PLL-PEG-PLL on HI/RPI.. PLL-PEG-PLL was synthesized and estimated by being applied as a nanocarrier for lengthening delivery of exenatide. Exenatide was loaded into PLL-PEG-PLL by electrostatic interactions at pH 7.4. The loading and release of exenatide from PLL-PEG-PLL were characterized in vitro. The pancreatic protection of exenatide/PLL-PEG-PLL was assessed using the animal model, histopathological examination, blood biochemical indices detection, antioxidant activity, and anti-inflammatory evaluation in vivo.. Exenatide/PLL-PEG-PLL displayed efficient loading and sustained release. Exenatide/PLL-PEG-PLL complex moderated HI/RPI and enlarged islet functionality compared to free exenatide.. We propose that the nanocarrier PLL-PEG-PLL may function as a potent exenatide nanocarrier for augmenting anti-HI/RPI pharmacotherapy with unprecedented clinical benefits.

Topics: Animals; Disease Models, Animal; Exenatide; Hypoglycemic Agents; Liver; Male; Nanoparticles; Pancreatic Diseases; Rats; Rats, Sprague-Dawley; Reperfusion Injury