Protective Effects of Glucagon-Like Peptide-1 Analog on Renal Tubular Injury in Mice on High-Fat Diet

Abstract

Aims: The study aimed to investigate the renoprotective effect of glucagon-like peptide-1 (GLP-1) against renal tubular injury in C57BL/6 mice induced by a high-fat diet (HFD). Methods: Twenty C57BL/6 mice were fed HFD for 12 weeks. Ten of these mice were treated with GLP-1 at 200 µg/kg subcutaneously twice daily for 4 weeks (HFDG group), and the other ten mice received vehicle only (HFD group). Ten mice fed standard rodent chow served as controls (Con group). Body weight, kidney weight, food intake, and systolic blood pressure were measured. The expression of endoplasmic reticulum stress (ERS) markers (BIP, p-eIF2α, ATF4, and CHOP) and apoptosis in the kidney were examined utilizing western blotting, immunohistochemistry and TUNEL, respectively. Angiotensin II and angiotensin II type 1 receptor (AT1R) were examined by ELISA. Human proximal tubule epithelial cells (HK2) were treated with GLP-1(150 nM) followed by treatment with palmitic acid (500 nM [PA]) for 24 h. HK2 cells treated with BSA were used as controls. The protein levels of ERS markers, apoptosis-associated protein, and AT1R were measured by western blotting. Results: Increase of body weight, food intake, and systolic blood pressure was less pronounced in GLP-1 treated HFDG mice compared to HFD mice. The levels of ERS markers (BIP, p-eIF2α, ATF4, and CHOP) and apoptosis decreased following GLP-1 treatment in vivo and in vitro (p<0.05). Increased AT1R induced by HFD and PA were blocked with GLP-1 treatment. In contrast, the level of angiotensin II after GLP-1 treatment was not significantly different between the HFD and HFDG mice. Conclusion: The study indicated that saturated fatty acids induced ERS and apoptosis in the kidney and increased AT1R expression. GLP-1 treatment exerted renoprotective effects against saturated fatty acid-induced kidney tubular cell ERS and apoptosis together with inhibition of AT1R expression in vivo and in vitro.

Largest single‐centre experience of dulaglutide for management of diabetes mellitus in solid organ transplant recipients

“…Liraglutide has been shown to ameliorate early renal injury by activation of the renal Forkhead box protein O1 (FoxO1) in a type 2 diabetic kidney rat model . Pre‐clinical animal studies showed a GLP1‐analog to have a protective effect against saturated fatty acid‐induced kidney tubular cell endoplasmic reticulum stress, and apoptosis, both in vivo and in vitro . Additionally, the reduction in renal injury could be attributed to decreased glucose drag and glomerular hyperfiltration in the setting of obesity during dulaglutide treatment.…”

“…10 Pre-clinical animal studies showed a GLP1-analog to have a protective effect against saturated fatty acid-induced kidney tubular cell endoplasmic reticulum stress, and apoptosis, both in vivo and in vitro. 11 Additionally, the reduction in renal injury could be attributed to decreased glucose drag and glomerular hyperfiltration in the setting of obesity during dulaglutide treatment. Thus, dulaglutide could be regarded as a valuable asset in the management of type 2 diabetes in SOT patients with renal dysfunction and metabolic syndrome.…”

Antibody Engineering for Pursuing a Healthier Future

“…IHC has recently been used for determination and identification of expressed proteins such as lysosome-associated protein transmembrane-4 beta (LAPTM4B) associated with the prognosis of several human malignancies (Xiao et al, 2017), glucagon-like peptide-1 (GLP-1) against renal tubular injury (Guo et al, 2017), and CD147 trans-membrane protein that induces expression and activity of matrix metalloproteinases (MMP) (Dana et al, 2016).…”

The glucagon‐like peptide‐1 receptor agonist Exendin‐4, ameliorates contrast‐induced nephropathy through suppression of oxidative stress, vascular dysfunction and apoptosis independent of glycaemia

“…61 Finally, and with regard to apoptosis, it has been suggested that GLP-1R agonists exert renoprotective effects by targeting cAMP and phosphatidylinositol 3-kinase dependent signalling pathway, which is known to inhibit apoptosis. 62 Other studies documented that anti-apoptotic effect of exendine-4 is by decreasing caspase-3 activity in renal tissue of renal ischaemia reperfusion models. 63 To our knowledge, our study is the first to demonstrate the reno- Bearing in mind the current pharmaceutical use of exendin-4 as a glycaemic control agent, our findings proposes exendine-4 as a promising candidate for prophylactic therapy against CIN in humans, particularly diabetic and renal impairment patients.…”

“…With regard to endothelial dysfunction, it has been postulated that phosphorylation of nuclear factor‐kappa B (NF‐kB), a key nucleus transcriptional factor which regulates the expression of a number of genes may play a key role in the reduction in endothelin‐1 expression as well as in the increase in eNOS expression by GLP‐1R agonists in the endothelial cells . Finally, and with regard to apoptosis, it has been suggested that GLP‐1R agonists exert renoprotective effects by targeting cAMP and phosphatidylinositol 3‐kinase dependent signalling pathway, which is known to inhibit apoptosis . Other studies documented that anti‐apoptotic effect of exendine‐4 is by decreasing caspase‐3 activity in renal tissue of renal ischaemia reperfusion models …”