IGF-1 ameliorates streptozotocin-induced pancreatic β cell dysfunction and apoptosis via activating IRS1/PI3K/Akt/FOXO1 pathway

Fan, Chun‐An; He, Xin

doi:10.1007/s00011-022-01557-3

Cited by 10 publications

(6 citation statements)

References 31 publications

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“…treatment enhanced the viability of STZ-treated islet cells [38]. IGF-1 treatment reversed the inhibition of STZ on the expression of IRS1, p-PI3K, p-Akt, and p-FOXO1, and the insulin secretion of islet cells increased significantly.…”

Section: Discussionmentioning

confidence: 90%

Polygonatum Sibiricum Saponin-Lactic acid bacteria combination attenuate hyperglycemia in T2DM mice by modulating amino acid metabolism

Luo,

Jia,

Liang

et al. 2024

Food Science and Human Wellness

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Some researches have shown that the combination of plant extracts and probiotics may be a better way to treat type 2 diabetes mellitus (T2DM) than a single intervention. However, there are still relatively few relevant reports in this aspect. Therefore, this study aims to investigate whether the treatment of polygonatum sibiricum saponin (PSS) and lactic acid bacteria (LAB) combination can better manage T2DM. And the anti-diabetes mechanism of the combination was studied from the perspectives of glucose metabolism, microbiome and metabolome. The results showed that PSS+LAB could better improve FBG level, insulin sensitivity, lipid metabolism disorder, and liver function. Protein analysis showed that PSS+LAB treatment significantly increased the expression of p-PI3K/PI3K, p-AKT/AKT, GLUT2, IRS2, and GSK-3β in the liver of T2DM mice, while inhibiting the expression of FOXO1. This combination positively regulated the composition and abundance of the gut microbiota. Metabolomic analysis showed that the combination treatment exhibited more changes in gut microbiota metabolites compared to PSS treatment alone. The alteration of gut microbiota by LAB+PSS led to significant changes in alanine, aspartate and glucose metabolism pathways. This study may provide a theoretical basis for the combined application of plant extracts and probiotics for the management of T2DM.

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Section: Discussionmentioning

confidence: 90%

Polygonatum Sibiricum Saponin-Lactic acid bacteria combination attenuate hyperglycemia in T2DM mice by modulating amino acid metabolism

Luo,

Jia,

Liang

et al. 2024

Food Science and Human Wellness

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show abstract

“…However, when GLUT4 was silenced, the improvements were partially reversed. These results suggested that, in addition to its relationship with GLUT4, IRS1 may regulate human pancreatic β cells through interactions with other target proteins, such as phosphoinositide-3-kinase/Akt [36], X-box binding protein-1 [37], free fatty acid receptor 1 [38], and glycogen synthase kinase-3β [39].…”

Section: Discussionmentioning

confidence: 98%

FGF19 Promotes the Proliferation and Insulin Secretion from Human Pancreatic β Cells Via the IRS1/GLUT4 Pathway

Zeng,

Tang,

Bai

et al. 2024

Exp Clin Endocrinol Diabetes

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Background Type 2 diabetes mellitus (T2DM) is a commonly observed complication associated with obesity. The effect of fibroblast growth factor 19 (FGF19), a promising therapeutic agent for metabolic disorders, on pancreatic β cells in obesity-associated T2DM remains poorly understood. Methods Human pancreatic β cells were cultured with high glucose (HG) and palmitic acid (PA), followed by treatment with FGF19. The cell proliferation, apoptosis, and insulin secretion were evaluated by CCK-8, qRT-PCR, ELISA, flow cytometry, and western blotting. The expression of the insulin receptor substrate (IRS)/glucose transporter (GLUT) pathway was evaluated. The interaction between FGF19 and IRS1 was predicted using the STRING database and verified by co-immunoprecipitation and immunofluorescence. The regulatory effects of the IRS1/GLUT4 pathway on human pancreatic β cells were assessed by overexpressing IRS1 and silencing IRS1 and GLUT4. Results HG+PA treatment reduced the human pancreatic β cell proliferation and insulin secretion and promoted cell apoptosis. However, FGF19 treatment restored these alterations and significantly increased the expressions of IRS1, GLUT1, and GLUT4 in the IRS/GLUT pathway. Furthermore, FGF19 and IRS1 were found to interact. IRS1 overexpression partially promoted the proliferation of pancreatic β cells and insulin secretion through GLUT4. Additionally, the silencing of IRS1 or GLUT4 attenuated the therapeutic effects of FGF19. Conclusion In conclusion, FGF19 partly promoted the proliferation and insulin secretion of human pancreatic β cells and inhibited apoptosis by upregulating the IRS1/GLUT4 pathway. These findings establish a theoretical framework for the clinical utilization of FGF19 in the treatment of obesity-associated T2DM.

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“…Studies have reported that iGF-i has strong anti-apoptotic activity in a variety of cell types and can protect cells through different apoptotic mechanisms (51)(52)(53). iGF-1 regulates Pi3K/aKT/Forkhead box o signaling to reduce cytochrome c levels in the cytoplasm, thereby suppressing cleaved caspase-3 formation and apoptosis (41,54,55). another study demonstrated that iGF-1 can reduce lipopolysaccharide-induced neuronal apoptosis through the mitochondrial pathway (41).…”

Section: Discussionmentioning

confidence: 99%

IGF‑1 inhibits palmitic acid‑induced mitochondrial apoptosis in macrophages

Tang,

Zhang,

Wang

et al. 2023

Mol Med Rep

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insulin growth factor-1 (iGF-1) is an endocrine regulator that plays an important role in normal growth and development. iGF-1 mediated effects may result in protecting macrophages from immunometabolic response. However, it is unclear whether iGF-1 has a protective effect on fatty acid-induced macrophages damage. in the present study, THP-1 cells were differentiated into macrophages and stimulated with palmitic acid (Pa) in the absence or presence of iGF-1. Macrophages apoptosis was measured by cell counting Kit-8 assay, flow cytometry, Hoechst 33342 staining and western blotting. The mitochondrial damage was evaluated using Jc-1 staining and mitochondrial reactive oxygen species detection. The activation of mitophagy was assessed using immunofluorescence and western blotting. As a result, IGF-1 significantly restored the survival rate in macrophages, while the apoptosis was inhibited through mitochondrial pathway. in addition, iGF-1 protected the mitochondrial damage induced by Pa. Furthermore, Pa induced mitophagy via phosphatase and tensin homolog-induced putative kinase protein 1/Parkin, which was reversed by iGF-1. Taken together, the present study demonstrated the protective effect of iGF-1 on Pa-induced mitochondrial apoptosis in macrophages, which might provide a potential therapeutic strategy for treatment of lipotoxicity.

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IGF-1 ameliorates streptozotocin-induced pancreatic β cell dysfunction and apoptosis via activating IRS1/PI3K/Akt/FOXO1 pathway

Cited by 10 publications

References 31 publications

Polygonatum Sibiricum Saponin-Lactic acid bacteria combination attenuate hyperglycemia in T2DM mice by modulating amino acid metabolism

Polygonatum Sibiricum Saponin-Lactic acid bacteria combination attenuate hyperglycemia in T2DM mice by modulating amino acid metabolism

FGF19 Promotes the Proliferation and Insulin Secretion from Human Pancreatic β Cells Via the IRS1/GLUT4 Pathway

IGF‑1 inhibits palmitic acid‑induced mitochondrial apoptosis in macrophages

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