Junqin Chen - Academia.edu (original) (raw)

Papers by Junqin Chen

Research paper thumbnail of Calcium Channel Blockers Act through Nuclear Factor Y to Control Transcription of Key Cardiac Genes

Molecular Pharmacology, Jun 25, 2012

Research paper thumbnail of TXNIP regulates myocardial fatty acid oxidation via miR-33a signaling

American Journal of Physiology-heart and Circulatory Physiology, Jul 1, 2016

Research paper thumbnail of Generation of a conditional null allele of jumonji

Research paper thumbnail of Intracellular Shuttling and Mitochondrial Function of Thioredoxin-interacting Protein

Journal of Biological Chemistry, Feb 1, 2010

Research paper thumbnail of Exploratory study reveals far reaching systemic and cellular effects of verapamil treatment in subjects with type 1 diabetes

Nature Communications, Mar 3, 2022

Research paper thumbnail of JUMONJI, a Critical Factor for Cardiac Development, Functions as a Transcriptional Repressor

Journal of Biological Chemistry, Oct 1, 2003

Research paper thumbnail of miR-204 Targets PERK and Regulates UPR Signaling and β-Cell Apoptosis

Molecular Endocrinology, Aug 1, 2016

Research paper thumbnail of Jumonji Represses Atrial Natriuretic Factor Gene Expression by Inhibiting Transcriptional Activities of Cardiac Transcription Factors

Molecular and Cellular Biology, Dec 1, 2004

Research paper thumbnail of Human Glucagon Expression Is under the Control of miR-320a

Endocrinology, 2020

Increased glucagon is a hallmark of diabetes and leads to worsening of the hyperglycemia, but the... more Increased glucagon is a hallmark of diabetes and leads to worsening of the hyperglycemia, but the molecular mechanisms causing it are still unknown. We therefore investigated the possibility that microRNAs might be involved in the regulation of glucagon. Indeed, analysis of the glucagon 3′ untranslated region (UTR) revealed potential binding sites for miR-320a, and using luciferase reporter assays we found that miR-320a directly targets the 3′ UTRs of human and rodent glucagon. In addition, endogenous glucagon mRNA and protein expression as well as glucagon secretion were reduced in response to miR-320a overexpression, whereas inhibition of miR-320a upregulated glucagon expression. Interestingly, miR-320a expression was decreased by high glucose, and this was associated with an increase in glucagon expression in human islets and mouse αTC1-6 cells. Moreover, miR-320a overexpression completely blunted these effects. Importantly, miR-320a was also significantly downregulated in human ...

Research paper thumbnail of miR-204 Controls Glucagon-Like Peptide 1 Receptor Expression and Agonist Function

Research paper thumbnail of Thioredoxin-interacting Protein Promotes Islet Amyloid Polypeptide Expression through miR-124a and FoxA2

Journal of Biological Chemistry, Apr 1, 2014

Background: Islet amyloid polypeptide (IAPP) plays an important role in beta-cell biology, but it... more Background: Islet amyloid polypeptide (IAPP) plays an important role in beta-cell biology, but its regulation is not fully understood. Results: Thioredoxin-interacting protein (TXNIP) induces IAPP by inhibiting miR-124a and promoting FoxA2-mediated transcription. Conclusion: The critical beta-cell signaling pathways of TXNIP and IAPP are linked. Significance: Identification of this novel TXNIP/miR-124a/FoxA2/IAPP signaling pathway provides new insight into an important aspect of transcriptional regulation and beta-cell biology.

Research paper thumbnail of Alpha Cell Thioredoxin-interacting Protein Deletion Improves Diabetes-associated Hyperglycemia and Hyperglucagonemia

Endocrinology

Thioredoxin-interacting protein (TXNIP) has emerged as a key factor in pancreatic beta cell biolo... more Thioredoxin-interacting protein (TXNIP) has emerged as a key factor in pancreatic beta cell biology, and its upregulation by glucose and diabetes contributes to the impairment in functional beta cell mass and glucose homeostasis. In addition, beta cell deletion of TXNIP protects against diabetes in different mouse models. However, while TXNIP is ubiquitously expressed, its role in pancreatic alpha cells has remained elusive. We generated an alpha cell TXNIP knockout (aTKO) mouse and assessed the effects on glucose homeostasis. While no significant changes were observed on regular chow, after a 30-week high-fat diet, aTKO animals showed improvement in glucose tolerance and lower blood glucose levels compared to their control littermates. Moreover, in the context of streptozotocin (STZ)-induced diabetes, aTKO mice showed significantly lower blood glucose levels compared to controls. While serum insulin levels were reduced in both control and aTKO mice, STZ-induced diabetes significant...

Research paper thumbnail of Preventing b-Cell Loss and Diabetes With Calcium Channel Blockers

Although loss of functional b-cell mass is a hallmark of diabetes, no treatment approaches that h... more Although loss of functional b-cell mass is a hallmark of diabetes, no treatment approaches that halt this process are currently available. We recently identified thioredoxin-interacting protein (TXNIP) as an attractive target in this regard. Glucose and di-abetes upregulate b-cell TXNIP expression, and TXNIP overex-pression induces b-cell apoptosis. In contrast, genetic ablation of TXNIP promotes endogenous b-cell survival and prevents strep-tozotocin (STZ)- and obesity-induced diabetes. Finding an oral medication that could inhibit b-cell TXNIP expression would therefore represent a major breakthrough. We were surprised to discover that calcium channel blockers inhibited TXNIP ex-pression in INS-1 cells and human islets and that orally adminis-tered verapamil reduced TXNIP expression and b-cell apoptosis, enhanced endogenous insulin levels, and rescued mice from STZ-induced diabetes. Verapamil also promoted b-cell survival and

Research paper thumbnail of Printed in Great Britain Competition

among three predominant ruminal cellulolytic bacteria in the absence or presence of non-celluloly... more among three predominant ruminal cellulolytic bacteria in the absence or presence of non-cellulolytic bacteria

Research paper thumbnail of miR-204 Antagomir Enhances GLP-1 Receptor Function and Glucose Control

Diabetes, 2018

Glucagon-like peptide 1 receptor (GLP-1R) is a G protein-coupled receptor that is highly expresse... more Glucagon-like peptide 1 receptor (GLP-1R) is a G protein-coupled receptor that is highly expressed on pancreatic beta-cells and activated by endogenous incretins or antidiabetic GLP-1R agonist drugs. GLP-1R function is important in maintaining glucose homeostasis and involves stimulation of glucose-induced beta-cell insulin secretion via cAMP generation. While GLP-1R expression has been shown to be downregulated in diabetes, the molecular mechanisms have not been fully elucidated. In this study, we have discovered that miR-204, a highly beta-cell-enriched microRNA that is upregulated in diabetes, directly targets the 3’ UTR of GLP-1R and decreases its expression in INS-1 cells as well as primary mouse and human islets. Moreover, genetic knockout of miR-204 in vivo increased islet GLP-1R expression and enhanced GLP-1R agonist-induced cAMP production and insulin secretion, resulting in improved glucose tolerance as well as protection against diabetes. In addition, miR-204 antagomir ad...

Research paper thumbnail of Deletion of Gdf15 reduces ER stress-induced beta cell apoptosis and diabetes

Endocrinology

Endoplasmic reticulum (ER) stress contributes to pancreatic beta cell apoptosis in diabetes, but ... more Endoplasmic reticulum (ER) stress contributes to pancreatic beta cell apoptosis in diabetes, but the factors involved are still not fully elucidated. Growth differentiation factor 15 (GDF15) is a stress response gene and has been reported to be increased and play an important role in various diseases. However, the role of GDF15 in beta cells in the context of ER stress and diabetes is still unclear. In this study, we have discovered that GDF15 promotes ER stress-induced beta cell apoptosis and that downregulation of GDF15 has beneficial effects on beta cell survival in diabetes. Specifically, we found that GDF15 is induced by ER stress in beta cells and human islets, and that the transcription factor C/EBPβ is involved in this process. Interestingly, ER stress-induced apoptosis was significantly reduced in INS-1 cells with Gdf15 knockdown and in isolated Gdf15 knockout mouse islets. In vivo, we found that Gdf15 deletion attenuates streptozotocin-induced diabetes by preserving beta c...

Research paper thumbnail of Through

protein regulates insulin transcription

Research paper thumbnail of Running title: TXNIP links glucotoxicity and beta cell death Corresponding Author

TXNIP links glucotoxicity and beta cell death

Research paper thumbnail of 2008), Price increasing competition

among three predominant ruminal cellulolytic bacteria in the absence or presence of non-celluloly... more among three predominant ruminal cellulolytic bacteria in the absence or presence of non-cellulolytic bacteria

Research paper thumbnail of Content Alerts

This article cites 50 articles, 27 of which can be accessed free

Research paper thumbnail of Calcium Channel Blockers Act through Nuclear Factor Y to Control Transcription of Key Cardiac Genes

Molecular Pharmacology, Jun 25, 2012

Research paper thumbnail of TXNIP regulates myocardial fatty acid oxidation via miR-33a signaling

American Journal of Physiology-heart and Circulatory Physiology, Jul 1, 2016

Research paper thumbnail of Generation of a conditional null allele of jumonji

Research paper thumbnail of Intracellular Shuttling and Mitochondrial Function of Thioredoxin-interacting Protein

Journal of Biological Chemistry, Feb 1, 2010

Research paper thumbnail of Exploratory study reveals far reaching systemic and cellular effects of verapamil treatment in subjects with type 1 diabetes

Nature Communications, Mar 3, 2022

Research paper thumbnail of JUMONJI, a Critical Factor for Cardiac Development, Functions as a Transcriptional Repressor

Journal of Biological Chemistry, Oct 1, 2003

Research paper thumbnail of miR-204 Targets PERK and Regulates UPR Signaling and β-Cell Apoptosis

Molecular Endocrinology, Aug 1, 2016

Research paper thumbnail of Jumonji Represses Atrial Natriuretic Factor Gene Expression by Inhibiting Transcriptional Activities of Cardiac Transcription Factors

Molecular and Cellular Biology, Dec 1, 2004

Research paper thumbnail of Human Glucagon Expression Is under the Control of miR-320a

Endocrinology, 2020

Increased glucagon is a hallmark of diabetes and leads to worsening of the hyperglycemia, but the... more Increased glucagon is a hallmark of diabetes and leads to worsening of the hyperglycemia, but the molecular mechanisms causing it are still unknown. We therefore investigated the possibility that microRNAs might be involved in the regulation of glucagon. Indeed, analysis of the glucagon 3′ untranslated region (UTR) revealed potential binding sites for miR-320a, and using luciferase reporter assays we found that miR-320a directly targets the 3′ UTRs of human and rodent glucagon. In addition, endogenous glucagon mRNA and protein expression as well as glucagon secretion were reduced in response to miR-320a overexpression, whereas inhibition of miR-320a upregulated glucagon expression. Interestingly, miR-320a expression was decreased by high glucose, and this was associated with an increase in glucagon expression in human islets and mouse αTC1-6 cells. Moreover, miR-320a overexpression completely blunted these effects. Importantly, miR-320a was also significantly downregulated in human ...

Research paper thumbnail of miR-204 Controls Glucagon-Like Peptide 1 Receptor Expression and Agonist Function

Research paper thumbnail of Thioredoxin-interacting Protein Promotes Islet Amyloid Polypeptide Expression through miR-124a and FoxA2

Journal of Biological Chemistry, Apr 1, 2014

Background: Islet amyloid polypeptide (IAPP) plays an important role in beta-cell biology, but it... more Background: Islet amyloid polypeptide (IAPP) plays an important role in beta-cell biology, but its regulation is not fully understood. Results: Thioredoxin-interacting protein (TXNIP) induces IAPP by inhibiting miR-124a and promoting FoxA2-mediated transcription. Conclusion: The critical beta-cell signaling pathways of TXNIP and IAPP are linked. Significance: Identification of this novel TXNIP/miR-124a/FoxA2/IAPP signaling pathway provides new insight into an important aspect of transcriptional regulation and beta-cell biology.

Research paper thumbnail of Alpha Cell Thioredoxin-interacting Protein Deletion Improves Diabetes-associated Hyperglycemia and Hyperglucagonemia

Endocrinology

Thioredoxin-interacting protein (TXNIP) has emerged as a key factor in pancreatic beta cell biolo... more Thioredoxin-interacting protein (TXNIP) has emerged as a key factor in pancreatic beta cell biology, and its upregulation by glucose and diabetes contributes to the impairment in functional beta cell mass and glucose homeostasis. In addition, beta cell deletion of TXNIP protects against diabetes in different mouse models. However, while TXNIP is ubiquitously expressed, its role in pancreatic alpha cells has remained elusive. We generated an alpha cell TXNIP knockout (aTKO) mouse and assessed the effects on glucose homeostasis. While no significant changes were observed on regular chow, after a 30-week high-fat diet, aTKO animals showed improvement in glucose tolerance and lower blood glucose levels compared to their control littermates. Moreover, in the context of streptozotocin (STZ)-induced diabetes, aTKO mice showed significantly lower blood glucose levels compared to controls. While serum insulin levels were reduced in both control and aTKO mice, STZ-induced diabetes significant...

Research paper thumbnail of Preventing b-Cell Loss and Diabetes With Calcium Channel Blockers

Although loss of functional b-cell mass is a hallmark of diabetes, no treatment approaches that h... more Although loss of functional b-cell mass is a hallmark of diabetes, no treatment approaches that halt this process are currently available. We recently identified thioredoxin-interacting protein (TXNIP) as an attractive target in this regard. Glucose and di-abetes upregulate b-cell TXNIP expression, and TXNIP overex-pression induces b-cell apoptosis. In contrast, genetic ablation of TXNIP promotes endogenous b-cell survival and prevents strep-tozotocin (STZ)- and obesity-induced diabetes. Finding an oral medication that could inhibit b-cell TXNIP expression would therefore represent a major breakthrough. We were surprised to discover that calcium channel blockers inhibited TXNIP ex-pression in INS-1 cells and human islets and that orally adminis-tered verapamil reduced TXNIP expression and b-cell apoptosis, enhanced endogenous insulin levels, and rescued mice from STZ-induced diabetes. Verapamil also promoted b-cell survival and

Research paper thumbnail of Printed in Great Britain Competition

among three predominant ruminal cellulolytic bacteria in the absence or presence of non-celluloly... more among three predominant ruminal cellulolytic bacteria in the absence or presence of non-cellulolytic bacteria

Research paper thumbnail of miR-204 Antagomir Enhances GLP-1 Receptor Function and Glucose Control

Diabetes, 2018

Glucagon-like peptide 1 receptor (GLP-1R) is a G protein-coupled receptor that is highly expresse... more Glucagon-like peptide 1 receptor (GLP-1R) is a G protein-coupled receptor that is highly expressed on pancreatic beta-cells and activated by endogenous incretins or antidiabetic GLP-1R agonist drugs. GLP-1R function is important in maintaining glucose homeostasis and involves stimulation of glucose-induced beta-cell insulin secretion via cAMP generation. While GLP-1R expression has been shown to be downregulated in diabetes, the molecular mechanisms have not been fully elucidated. In this study, we have discovered that miR-204, a highly beta-cell-enriched microRNA that is upregulated in diabetes, directly targets the 3’ UTR of GLP-1R and decreases its expression in INS-1 cells as well as primary mouse and human islets. Moreover, genetic knockout of miR-204 in vivo increased islet GLP-1R expression and enhanced GLP-1R agonist-induced cAMP production and insulin secretion, resulting in improved glucose tolerance as well as protection against diabetes. In addition, miR-204 antagomir ad...

Research paper thumbnail of Deletion of Gdf15 reduces ER stress-induced beta cell apoptosis and diabetes

Endocrinology

Endoplasmic reticulum (ER) stress contributes to pancreatic beta cell apoptosis in diabetes, but ... more Endoplasmic reticulum (ER) stress contributes to pancreatic beta cell apoptosis in diabetes, but the factors involved are still not fully elucidated. Growth differentiation factor 15 (GDF15) is a stress response gene and has been reported to be increased and play an important role in various diseases. However, the role of GDF15 in beta cells in the context of ER stress and diabetes is still unclear. In this study, we have discovered that GDF15 promotes ER stress-induced beta cell apoptosis and that downregulation of GDF15 has beneficial effects on beta cell survival in diabetes. Specifically, we found that GDF15 is induced by ER stress in beta cells and human islets, and that the transcription factor C/EBPβ is involved in this process. Interestingly, ER stress-induced apoptosis was significantly reduced in INS-1 cells with Gdf15 knockdown and in isolated Gdf15 knockout mouse islets. In vivo, we found that Gdf15 deletion attenuates streptozotocin-induced diabetes by preserving beta c...

Research paper thumbnail of Through

protein regulates insulin transcription

Research paper thumbnail of Running title: TXNIP links glucotoxicity and beta cell death Corresponding Author

TXNIP links glucotoxicity and beta cell death

Research paper thumbnail of 2008), Price increasing competition

among three predominant ruminal cellulolytic bacteria in the absence or presence of non-celluloly... more among three predominant ruminal cellulolytic bacteria in the absence or presence of non-cellulolytic bacteria

Research paper thumbnail of Content Alerts

This article cites 50 articles, 27 of which can be accessed free