Leptin receptor mediates the proliferation and glucose metabolism of pancreatic cancer cells via AKT pathway activation

Abstract

Pancreatic cancer (Pc) is the fourth leading cause of cancer-related mortality worldwide. leptin is an adipokine that is significantly increased in obese patients and that functions in various biological processes of cancer, such as tumor growth and metastasis. However, its role in Pc cell proliferation and glucose metabolism and the underlying mechanisms remain unclear. in the present study, in vitro leptin treatment significantly promoted cell proliferation and increased glucose uptake and lactate production of human Pc and healthy pancreas cells in a dose-dependent manner, accompanied by increased expression of the glycolytic enzymes hexokinase ii and glucose transporter 1. Furthermore, leptin receptor-specific short hairpin rnas were used to silence leptin receptor expression in Pc cells, which had the opposite effect to leptin stimulation and decreased aKT phosphorylation. in addition, the effects of leptin stimulation were significantly counteracted by the AKT inhibitor LY294002, whereas the effects of leptin silencing were counteracted by AKT activator insulin-like growth factor 1. The results of the present study suggested that leptin may contribute to cell proliferation and glucose metabolism of human PC cells, which may be through activation of the aKT pathway.

Fat Body p53 Regulates Systemic Insulin Signaling and Autophagy under Nutrient Stress via Drosophila Upd2 Repression

“…The fact that p53 is activated in the adipose tissue of obese animals, along with the results here presented concerning a putative direct role of p53 in controlling Upd2/ Leptin expression, demonstrates the importance of p53 in regulating metabolism. This is particularly interesting given that epidemiological studies over the last few decades have shown a strong influence of obesity on cancer risk and that increased Leptin can have hormone-like functions affecting tumor development (Andò et Singh et al, 2020;Xu et al, 2020). In this context, our results give insights toward the molecular understanding of p53 activation under metabolic stress and its possible role in tumor suppression acting at either local or organismal level.…”

Cooperative effects of galanin and leptin on alleviation of insulin resistance in adipose tissue of diabetic rats

“…35,36 Recent studies showed that leptin receptor mediated the regulation of the glucose metabolism via activation of AKT pathway. 37 The AKT inhibitor can significantly counteracted the effect of leptin, and AKT activator can counteracted the effect of leptin silencing. In addition, galanin can benefit glucose uptake via inhibition of adenylyl cyclase and cAMP through Gi/o receptors to activate the PI3K/Akt signalling pathway too.…”

Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments

“…Oncogenic hypoxia inducible factor (HIF)-1α was identified to bind directly to hypoxiaresponsive elements (HREs) located in the LEPR gene promoter (-828/-832), thereby activating downstream transcriptional events in pancreatic cancer cells, suggesting the potential significance of the leptin receptor-mediated axis during hypoxia [81]. In a study of pancreatic cancer, the results demonstrated that exogeneous leptin could enhance cell proliferation, glucose uptake and lactate production in a dose-dependent manner, and that this was accompanied by elevated expression of the glycolytic enzymes hexokinase II and glucose transporter 1, suggesting the potential involvement of glucose metabolism in pancreatic cancer progression [82]. In addition, simultaneously high leptin receptor and MMP13 production exhibited a positive correlation with TNM status in pancreatic cancer patients.…”

“…↑: [67,70] ↑: [67] ↓: [66] Lung Cancer ↑: [79,80] ↑: [76,77,80] ↑: (erlotinib) [78], (cisplatin) [79] Pancreatic Cancer ↑: [82,87,88] ↑: [83] ↑: (gemcitabine) [86], (5-FU) [87] Prostate Cancer ↑: [89] ↑: [89,90] ↓: [89] Gallbladder cancer ↑: [91] Myeloma ↑: (bortezomib) [92] Chondrosarcoma ↑: [93,94] ↑: increase.↓: decrease.…”