Diacylglycerol Signaling Pathway in Pancreatic β-Cells: An Essential Role of Diacylglycerol Kinase in the Regulation of Insulin Secretion

Kaneko, Yukiko; Ishikawa, Tomohisa

doi:10.1248/bpb.b15-00060

Cited by 25 publications

(17 citation statements)

References 37 publications

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“…DAG plays essential roles in β cells, both acting as a second messenger for cellular signaling and as backbone for lipid synthesis. DAG also affects insulin secretion from β cells (14, 16, 17, 32). Therefore, we aimed to find out if E‐Syt1—mediated ER‐PM contacts regulate DAG in β cells.…”

Section: Resultsmentioning

confidence: 99%

Feedback regulation of insulin secretion by extended synaptotagmin‐1

2018

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Endoplasmic reticulum (ER)—plasma membrane (PM) contacts are dynamic structures with important roles in the regulation of calcium (Ca2+) and lipid homeostasis. The extended synaptotagmins (E‐Syts) are ER‐localized lipid transport proteins that interact with PM phosphatidylinositol 4,5‐bisphosphate in a Ca2+‐dependent manner. E‐Syts bidirectionally transfer glycerolipids, including diacylglycerol (DAG), between the 2 juxtaposed membranes, but the biologic significance of this transport is still unclear. Using insulin‐secreting cells and live‐cell imaging, we now show that Ca2+‐triggered exocytosis of insulin granules is followed, in sequence, by PM DAG formation and E‐Syt1 recruitment. E‐Syt1 counteracted the depolarization‐induced DAG formation through a mechanism that required both voltage‐dependent Ca2+ influx and Ca2+ release from the ER. E‐Syt1 knockdown resulted in prolonged accumulation of DAG in the PM, resulting in increased glucose‐stimulated insulin secretion. We conclude that Ca2+‐triggered exocytosis is temporally coupled to Ca2+‐triggered E‐Syt1 PM recruitment and removal of DAG to negatively regulate the same process.—Xie, B., Nguyen, P. M., Idevall‐Hagren, O. Feedback regulation of insulin secretion by extended synaptotagmin‐1. FASEB J. 33, 4716–4728 (2019). http://www.fasebj.org

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Section: Resultsmentioning

confidence: 99%

Feedback regulation of insulin secretion by extended synaptotagmin‐1

2018

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“…Three genes related with lipid metabolism are located in this region: Lipase H (LIPH ), a member of the mammalian triglyceride lipase family; diacylglycerol kinase gamma-like (DGKG ), a member of the type I subfamily of diacylglycerol kinases that catalyzes the phosphorylation of the lipid second messenger diacylglycerol (DAG) to phosphatidic acid44; and phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA ), which encodes a catalytic subunit of the class IA phosphoinositide 3-kinases (PI3Ks). Interestingly, that gene is a key mediator of the hepatic insulin signaling, regulating glucose and lipid metabolism through the Akt/PKB pathway45.…”

Section: Resultsmentioning

confidence: 99%

Integration of liver gene co-expression networks and eGWAs analyses highlighted candidate regulators implicated in lipid metabolism in pigs

Ballester

Ramayo-Caldas

Revilla

et al. 2017

Sci Rep

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In the present study, liver co-expression networks and expression Genome Wide Association Study (eGWAS) were performed to identify DNA variants and molecular pathways implicated in the functional regulatory mechanisms of meat quality traits in pigs. With this purpose, the liver mRNA expression of 44 candidates genes related with lipid metabolism was analysed in 111 Iberian x Landrace backcross animals. The eGWAS identified 92 eSNPs located in seven chromosomal regions and associated with eight genes: CROT, CYP2U1, DGAT1, EGF, FABP1, FABP5, PLA2G12A, and PPARA. Remarkably, cis-eSNPs associated with FABP1 gene expression which may be determining the C18:2(n-6)/C18:3(n-3) ratio in backfat through the multiple interaction of DNA variants and genes were identified. Furthermore, a hotspot on SSC8 associated with the gene expression of eight genes was identified and the TBCK gene was pointed out as candidate gene regulating it. Our results also suggested that the PI3K-Akt-mTOR pathway plays an important role in the control of the analysed genes highlighting nuclear receptors as the NR3C1 or PPARA. Finally, sex-dimorphism associated with hepatic lipid metabolism was identified with over-representation of female-biased genes. These results increase our knowledge of the genetic architecture underlying fat composition traits.

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“…High levels of saturated FFA have been suggested to be correlated with impaired glucose tolerance in both T1DM and T2DM (Maulucci et al, 2016). Diacylglycerol signaling pathway regulates pancreatic β cells and insulin secretion (Kaneko and Ishikawa, 2015). Ceramide also plays a critical role in DM development (Galadari et al, 2013).…”

Section: Influence Of Pei and Malnutritionmentioning

confidence: 99%

Pathological Mechanisms in Diabetes of the Exocrine Pancreas: What’s Known and What’s to Know

Wei

Lin

et al. 2020

Front. Physiol.

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The clinical significance of diabetes arising in the setting of pancreatic disease (also known as diabetes of the exocrine pancreas, DEP) has drawn more attention in recent years. However, significant improvements still need to be made in the recognition, diagnosis and treatment of the disorder, and in the knowledge of the pathological mechanisms. The clinical course of DEP is different from type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). DEP develops in patients with previous existing exocrine pancreatic disorders which damage both exocrine and endocrine parts of pancreas, and lead to pancreas exocrine insufficiency (PEI) and malnutrition. Therefore, damage in various exocrine and endocrine cell types participating in glucose metabolism regulation likely contribute to the development of DEP. Due to the limited amount of clinical and experimental studies, the pathological mechanism of DEP is poorly defined. In fact, it still not entirely clear whether DEP represents a distinct pathologic entity or is a form of T2DM arising when β cell failure is accelerated by pancreatic disease. In this review, we include findings from related studies in T1DM and T2DM to highlight potential pathological mechanisms involved in initiation and progression of DEP, and to provide directions for future research studies.

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Diacylglycerol Signaling Pathway in Pancreatic β-Cells: An Essential Role of Diacylglycerol Kinase in the Regulation of Insulin Secretion

Cited by 25 publications

References 37 publications

Feedback regulation of insulin secretion by extended synaptotagmin‐1

Feedback regulation of insulin secretion by extended synaptotagmin‐1

Integration of liver gene co-expression networks and eGWAs analyses highlighted candidate regulators implicated in lipid metabolism in pigs

Pathological Mechanisms in Diabetes of the Exocrine Pancreas: What’s Known and What’s to Know

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