GLP-1 (Glucagon-like peptide-1)  is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. Importantly, GLP-1 promotes insulin secretion in a glucose-dependent manner. Particularly, GLP-1 ensures the β cell insulin stores by promoting insulin gene transcription, mRNA stability, and biosynthesis. Specifically, GLP-1 also increases β cell mass by promoting proliferation and neogenesis while inhibiting apoptosis. Meanwhile, GLP-1 receptor activation links with neurotrophic effects, including neurogenesis and neuroprotective effects, including reduced necrotic and apoptotic signaling, cell death, and dysfunctions.

In this article, we will introduce a GLP-1 receptor agonist, Liraglutide.

Liraglutide is a synthetic analog of glucagon-like peptide-1, which is utilized in the treatment of type 2 diabetes and obesity. Besides, Liraglutide dose-dependently attenuates the osteoblastic differentiation of MC3T3-E1 cells. Moreover, Liraglutide upregulates p-AMPK and downregulates p-mTOR and TGF-β protein expression levels. Meanwhile, Liraglutide (1-1000 nM; 48 h) significantly reduces high glucose (HG)-stimulated production of fibronectin, collagen type IV, and α-smooth muscle actin in human mesangial cells. In addition, Liraglutide (100 nM; 24 h) attenuates the HG-induced decrease in Wnt/β-catenin signaling proteins in HMCs.

Liraglutide (200 μg/kg/12 h, sc; 8 weeks) significantly improves elevated blood urine nitrogen, serum creatinine, and urinary albumin excretion rate and alleviates renal hypertrophy, mesangial expansion and glomerular fibrosis in streptozocin-induced type 1 diabetic rat. In contrast, blood glucose level and body weight did not have significant changes. Meanwhile, Liraglutide treatment significantly reduces the diabetes-induced increases in glomerular fibronectin, collagen type IV, and α-smooth muscle actin and decreases in glomerular Wnt/β-catenin signaling proteins.

All in all, Liraglutide is a potent GLP-1 receptor agonist and has the potential for Type 2 diabetes research.

Reference：

[1] Huang L, et al. Am J Physiol Renal Physiol. 2020 Sep 1;319(3):F458-F468.

[2] Hu XK, et al. Mol Med Rep. 2016 Oct;14(4):3662-8.