Geniposide accelerates proteasome degradation of Txnip to inhibit insulin secretion in pancreatic β-cells

Liu, C. Y.; Hao, Yanan; Yin, Fei; Zhang, Y. L.; Liu, J. H.

doi:10.1007/s40618-016-0591-9

Cited by 22 publications

(21 citation statements)

References 30 publications

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“…18,[32][33][34][35] Moreover, several studies had shown that Txnip was the critical link between glucotoxicity and beta cell apoptosis. [36][37][38] In this study, we showed that both Taken together, geniposide had been shown to regulate GSIS via regulating glucose uptake, ATP production, and Txnip degradation, 10,12,17 and prevented pancreatic beta cell apoptosis and dysfunction from palmitate and high glucose. 14,15 Here, we report a novel pathway of geniposide-regulating GSIS through ER stress with the phosphorylation of PERK and IRE1α.…”

Section: Discussionmentioning

confidence: 70%

“…Taken together, geniposide had been shown to regulate GSIS via regulating glucose uptake, ATP production, and Txnip degradation, and prevented pancreatic beta cell apoptosis and dysfunction from palmitate and high glucose . Here, we report a novel pathway of geniposide‐regulating GSIS through ER stress with the phosphorylation of PERK and IRE1α.…”

Section: Discussionmentioning

confidence: 78%

“…Our previous works showed that geniposide could accelerate Txnip degradation to inhibit GSIS in high glucose‐cultured INS‐1 cells . In this study, to investigate the role of PERK on geniposide‐regulating insulin secretion induced by high glucose in INS‐1 cells, we firstly determined the effect of GSK2656157, an inhibitor of PERK, on insulin secretion in 25 mM glucose‐incubated INS‐1 cells; the results indicated that geniposide decreased the insulin content in 25 mM glucose‐cultured INS‐1 cells, but pre‐incubation with GSK2656157 significantly prevented the effect of geniposide (Figure A).…”

Section: Resultsmentioning

confidence: 94%

“…Our previous works suggested that geniposide accelerated the degradation of Txnip to attenuate high glucose‐induced insulin secretion in pancreatic beta cells . To explore the role of Txnip on UPR in high glucose‐treated INS‐1 cells, we firstly knock down the expression of Txnip gene in INS‐1 cells with siRNA as described before, and then, we evaluated the effect of geniposide on the phosphorylation of PERK/eIF2α and IRE1α in normal cultured and Txnip‐knockdown INS‐1 cells.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous works showed that geniposide could accelerate Txnip degradation to inhibit GSIS in high glucose-cultured INS-1 cells. 17 Figure 5A). Moreover, in PERK knockdown-INS-1 cells, the inhibition of geniposide on GSIS was prevented ( Figure 5B).…”

Section: Effect Of Perk On Geniposide-regulating Glucose-stimulatedmentioning

confidence: 98%

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Unfolded protein response is involved in geniposide‐regulating glucose‐stimulated insulin secretion in INS‐1 cells

Hao

Shen

Yin

et al. 2019

Cell Biochemistry & Function

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The growing evidence shows that in the early stage of type 2 diabetes mellitus (T2DM) development, when challenged by hyperglycemia and/or insulin resistance, pancreatic islets would produce more insulin to maintain the balance of blood sugar, but at the same time, endoplasmic reticulum (ER) stress will be initiated for the reason of over‐compensation, which might be a crucial caused factor of dysfunction and death of pancreatic beta cell. In this study, we showed that high glucose induced a remarkably unfolded protein response (UPR) with the phosphorylation of PERK/eIF2α and IRE1α in INS‐1 cells, but geniposide prevented the role of high glucose on the phosphorylation of PERK/eIF2α and IRE1α, respectively. Although inhibition of Txnip expression by siRNA had no significant effect on geniposide‐regulating UPR, PERK and IRE1α were associated with geniposide‐regulating Txnip degradation and glucose‐stimulated insulin secretion (GSIS) in high glucose‐cultured INS‐1 cells. All these data suggest that geniposide might be an important regulator of ER stress and GSIS, and a promising compound for the treatment of T2DM. Significance of the study Mounting evidence indicates that endoplasmic reticulum (ER) stress plays an essential role to maintain the normal cellular functions and dysfunction. In this study, we revealed that geniposide might be an important regulator of ER stress and glucose‐stimulated insulin secretion in pancreatic beta cells.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 78%

Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Effect Of Perk On Geniposide-regulating Glucose-stimulatedmentioning

confidence: 98%

See 3 more Smart Citations

Unfolded protein response is involved in geniposide‐regulating glucose‐stimulated insulin secretion in INS‐1 cells

Hao

Shen

Yin

et al. 2019

Cell Biochemistry & Function

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Geniposide inhibits glucolipotoxicity and cooperates with Txnip knockdown to potentiate cell adaption to endoplasmic reticulum stress in pancreatic beta cells

Liu

Shen

et al. 2020

Cell Biology International

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Thioredoxin‐interacting protein (Txnip), a negative regulator of thioredoxin, has become an attractive therapeutic target to alleviate metabolic diseases. Our previous data demonstrated that geniposide improved glucose‐stimulated insulin secretion by accelerating Txnip degradation and prevented the early‐stage apoptosis of pancreatic β cells induced by palmitate, but the underlying mechanisms are still unclear. The objective of this study is to identify the role of Txnip in geniposide preventing the apoptosis of pancreatic β cells induced by high glucose and palmitate (HG/PA). The results revealed that geniposide attenuated HG/PA‐induced cell apoptosis and the expression of Bax and caspase‐3, while increasing mitochondrial membrane potential and the anti‐apoptotic protein levels of heme‐oxygenase‐1 (HO‐1) and Bcl‐2 in INS‐1 rat pancreatic β cells. Knockdown of the Txnip gene raised the levels of anti‐apoptotic proteins HO‐1 and Bcl‐2 and geniposide potentiated the effect of Txnip when the INS‐1 cells were challenged by HG/PA. Furthermore, geniposide enhanced the adoptive unfolded protein response by increasing the phosphorylation of PERK/eIF2α and IRE1α in HG/PA‐treated INS‐1 cells. The results together suggest that geniposide might be useful to antagonize glucolipotoxicity and Txnip might be a pleiotropic cellular factor in pancreatic β cells.

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Regulation of pancreatic exocrine in ruminants and the related mechanism: The signal transduction and more

2021

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The unique structure of the stomach, including the rumen, reticulum, omasum, and abomasum, indicates the differences between the ruminant and monogastric animals in the digestion of nutrients. This difference is reflected in the majority of dietary nutrients that may be fermented in the rumen. Significant proteins and a certain amount of starch can flow to the small intestine apart from rumen. The initial phase of small intestinal digestion requires pancreatic digestive enzymes. In theory, the enzymatic digestion and utilization efficiency of starch in the small intestine are considerably higher than that in the rumen, but the starch digestibility in the small intestine is quite low in ruminants. Therefore, improving the digestion of nutrients, especially starch in the small intestine is more urgent for high-yield ruminants. Although the pancreas plays a central role in nutrient digestion, the progress of research investigating pancreatic exocrine regulation in the ruminant is slow due to some factors, such as the complex structure of the pancreas, the selection of experimental model and duration, and internal (hormones or ages) and external (diet) influences. The present review is based on the research findings of pancreatic exocrine regulation of dairy animals and expounded from the physiological structure of the ruminant pancreas, the factors affecting the digestion and exocrine processing of carbohydrates, and the regulatory mechanism governing this process. The review aims to better understand the characteristics of enzymatic digestion, thereby advancing pancreatic exocrine research and improving the digestion and utilization of nutrients in ruminants. Additionally, this review provides the theoretical basis for improving nutrient utilization efficiency, reducing wastage of feed resources, and promoting the efficient development of the dairy industry.

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Geniposide accelerates proteasome degradation of Txnip to inhibit insulin secretion in pancreatic β-cells

Abstract: Txnip protein played an essential role in glucose uptake, metabolism and GSIS, and geniposide could accelerate the degradation via proteasome pathway in high-glucose-treated pancreatic INS-1 cells.

Cited by 22 publications

References 30 publications

Unfolded protein response is involved in geniposide‐regulating glucose‐stimulated insulin secretion in INS‐1 cells

Unfolded protein response is involved in geniposide‐regulating glucose‐stimulated insulin secretion in INS‐1 cells

Geniposide inhibits glucolipotoxicity and cooperates with Txnip knockdown to potentiate cell adaption to endoplasmic reticulum stress in pancreatic beta cells

Regulation of pancreatic exocrine in ruminants and the related mechanism: The signal transduction and more

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