Biophysical insights into glucose-dependent transcriptional regulation by PDX1

Usher, Grace A.; Showalter, Scott A.

doi:10.1016/j.jbc.2022.102623

Cited by 4 publications

(4 citation statements)

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“…For instance, the pancreatic transcription factor PDX-1, by regulating the insulin promoter, plays a key role in pancreatic β cell function [28]. It has been shown that both glucose and insulin stimulate PDX-1 binding activity, and reductions in PDX-1 expression may impair glucose-stimulated insulin secretion [29]. Our results revealed that some PL extracts could increase the insulin and PDX-1 gene expression in a high-glucose condition in INS-1E β cells, suggesting a protective role of PL extracts in the diabetic complications.…”

Section: Discussionmentioning

confidence: 99%

Novel role ofPeriploca laevigataextracts as anti-diabetic and anti-inflammatory function in pancreatic β cells exposed to hyperglycaemia

Trabelsi,

Mellado,

Kalboussi

et al. 2023

Preprint

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Type 2 Diabetes (T2D) is a major health problem worldwide. This metabolic disease is associated with high blood glucose levels due to insufficient insulin production by the pancreas, leading to an inflammatory immune response. Considering the beneficial roles of medicinal plants to control the diabetic complications of T2D, as well as the therapeutic roles of the extracts fromPeriploca laevigata(PL), this study evaluates the anti-diabetic and anti-inflammatory properties of PL extracts in the pancreatic β cell line INS-1E under hyperglycaemic. Our findings demonstrated, for the first time, that whereas PL extracts tends to upregulate the insulin gene expression, PL extract from leaves increase significantly the gene expression of GLUT-2 and the transcription factor PDX-1 in glucose-treated INS-1E cells. Notably, some PL extracts are also capable to decrease significantly the gene expression of iNOS and to increase the IL-10 gene expression in glucose-treated INS-1E cells. However, the PL extracts show a tendency to decrease the gene expression of NF-kB and MCP-1 in glucose-treated INS-1E cells. In conclusion, our findings suggest that the treatment with PL extracts could benefit the pancreatic β cell function and alleviate the pancreatic inflammation, thereby representing potential advantages of the glucose metabolism in the T2D.

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Section: Discussionmentioning

confidence: 99%

Novel role ofPeriploca laevigataextracts as anti-diabetic and anti-inflammatory function in pancreatic β cells exposed to hyperglycaemia

Trabelsi,

Mellado,

Kalboussi

et al. 2023

Preprint

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show abstract

“…Elevated intracellular Ca 2+ promotes cAMP formation by activating adenylyl cyclase. Increased cAMP activates protein kinase A (PKA) and cAMP-responsive element-binding protein (CREB) [ 32 ], the activity of which culminates in insulin secretion [ 33 , 34 ]. Either directly or indirectly, PKA activates pancreas duodenum homeobox-1 (PDX-1), which is an slc2a2 (GLUT2) transcription factor [ 33 , 34 , 35 ].…”

Section: Molecular and Cellular Basis Of T2d Pathogenesismentioning

confidence: 99%

“…Increased cAMP activates protein kinase A (PKA) and cAMP-responsive element-binding protein (CREB) [ 32 ], the activity of which culminates in insulin secretion [ 33 , 34 ]. Either directly or indirectly, PKA activates pancreas duodenum homeobox-1 (PDX-1), which is an slc2a2 (GLUT2) transcription factor [ 33 , 34 , 35 ]. It has been shown that the expression of PDX-1 restores the presence of functioning β-cells [ 36 ].…”

Section: Molecular and Cellular Basis Of T2d Pathogenesismentioning

confidence: 99%

The Perfect Cup? Coffee-Derived Polyphenols and Their Roles in Mitigating Factors Affecting Type 2 Diabetes Pathogenesis

Chapple,

Woodfin,

Moore

2024

Molecules

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Type 2 diabetes (T2D) is a growing health concern with an estimated 462 million people having been diagnosed worldwide. T2D is characterized by chronically elevated blood glucose and insulin resistance, which culminate in a diminished function of the β-cell mass in its later stages. This can be perpetuated by and result in inflammation, excess reactive oxygen species production, obesity, and the dysregulation of multiple cellular pathways. Many naturally occurring small molecules have been investigated in terms of their roles in modulating glucose homeostasis and β-cell function. Many of these compounds can be found in commonly used sources of food and drink. Interestingly, a correlation has been observed between coffee consumption and T2D incidence. However, the specific compounds responsible for this correlation and their mechanisms are still somewhat undetermined. This paper reviews recent research findings on the effects of several polyphenols that are either found in coffee or are metabolites of compounds found in coffee (enterodiol, enterolactone, matairesinol, secoisolariciresinol, kaempferol, quercetin, and chlorogenic acid) on glucose homeostasis and health complications associated with glucose dysregulation, with a special emphasis on their potential anti-diabetic effects. The factors that affect polyphenol content in coffee are also addressed.

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“…[13]. Furthermore, intrinsic disorder is tightly connected to the pathogenesis of various human diseases, since the majority of human cancer-associated proteins [7,[33][34][35][36][37][38][39][40]-as well as many proteins associated with neurodegeneration [41][42][43][44][45][46][47], diabetes [48][49][50][51], major psychiatric disorders [52], and cardiovascular diseases [48,[53][54][55][56][57]-are either intrinsically disordered or contain long IDPRs, giving rise to the D 2 (disorder in disorders) concept [58]. Curiously, based on the computational analysis of the diseasome network organized by human genetic diseases and related genes [59], it was concluded that this diseasome represents a human-genetic-diseaseassociated unfoldome, where intrinsic disorder and disorder-based interaction sites are commonly found in proteins associated with human genetic diseases and where proteins from different classes of genetic disease possess different levels of intrinsic disorder [60].…”

Section: Of 21mentioning

confidence: 99%

The Proteomic Analysis of Cancer-Related Alterations in the Human Unfoldome

Paromov,

Uversky,

Cooley

et al. 2024

IJMS

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Many proteins lack stable 3D structures. These intrinsically disordered proteins (IDPs) or hybrid proteins containing ordered domains with intrinsically disordered protein regions (IDPRs) often carry out regulatory functions related to molecular recognition and signal transduction. IDPs/IDPRs constitute a substantial portion of the human proteome and are termed “the unfoldome”. Herein, we probe the human breast cancer unfoldome and investigate relations between IDPs and key disease genes and pathways. We utilized bottom-up proteomics, MudPIT (Multidimensional Protein Identification Technology), to profile differentially expressed IDPs in human normal (MCF-10A) and breast cancer (BT-549) cell lines. Overall, we identified 2271 protein groups in the unfoldome of normal and cancer proteomes, with 148 IDPs found to be significantly differentially expressed in cancer cells. Further analysis produced annotations of 140 IDPs, which were then classified to GO (Gene Ontology) categories and pathways. In total, 65% (91 of 140) IDPs were related to various diseases, and 20% (28 of 140) mapped to cancer terms. A substantial portion of the differentially expressed IDPs contained disordered regions, confirmed by in silico characterization. Overall, our analyses suggest high levels of interactivity in the human cancer unfoldome and a prevalence of moderately and highly disordered proteins in the network.

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Biophysical insights into glucose-dependent transcriptional regulation by PDX1

Cited by 4 publications

References 200 publications

Novel role ofPeriploca laevigataextracts as anti-diabetic and anti-inflammatory function in pancreatic β cells exposed to hyperglycaemia

Novel role ofPeriploca laevigataextracts as anti-diabetic and anti-inflammatory function in pancreatic β cells exposed to hyperglycaemia

The Perfect Cup? Coffee-Derived Polyphenols and Their Roles in Mitigating Factors Affecting Type 2 Diabetes Pathogenesis

The Proteomic Analysis of Cancer-Related Alterations in the Human Unfoldome

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