Dual effect of reduced type I diacylglycerol kinase activity on insulin secretion from MIN6 β-cells

Sawatani, Toshiaki; Kaneko, Yukiko; Ishikawa, Tomohisa

doi:10.1016/j.jphs.2019.06.001

Cited by 7 publications

(3 citation statements)

References 36 publications

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“…Hence, maintaining pancreatic β-cell function is very important in reducing the onset and progression of diabetes, especially in Asians, and hence has been examined as a target for diabetes treatment. We have investigated the mechanisms for the regulation of insulin secretion in β-cells: regulation of insulin secretion by diacylglycerol (DAG), 4,5) a bioactive lipid; involvement of transient receptor potential vanilloid 2 (TRPV2) channel in the hypoosmoticinduced insulin secretory response 6) ; functioning of hydrogen sulfide, a gaseous signal molecule, as an insulin secretion inhibitory molecule, 7) and so on. This review focuses on the regulation of insulin secretion by type I diacylglycerol kinase (DGK), a DAG-metabolizing enzyme.…”

Section: Investigation Of the Mechanism Un-derlying Insulin Secretionmentioning

confidence: 99%

Development of Therapeutic Agents with a Novel Mechanism of Action Targeting Pancreatic β-Cells for Diabetes

Kaneko

2023

Biological & Pharmaceutical Bulletin

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Although diabetes is associated with an increased risk of various diseases, including cancer and infectious diseases, no definitive cure has yet been found. Long-term treatment for blood glucose control significantly reduces the QOL. Pancreatic β-cells are the only cells that can lower blood glucose levels by secreting insulin. Therefore, maintaining insulin-secreting β-cells is crucial in preventing the progression of diabetes and improving the QOL. We have investigated the mechanisms for the regulation of insulin secretion, the prevention of β-cell apoptosis, and the increase in β-cell mass. In particular, we have elucidated the involvement of type I diacylglycerol kinase (DGK) in the regulation of insulin secretion and the effects of nitric oxide (NO) signaling and natural products in suppressing β-cell death. In addition, we have elucidated the function of DGKδ as a suppressor of β-cell proliferation. This review introduces the findings of our study leading to development of novel anti-diabetic therapeutics that targets pancreatic β-cells.

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Section: Investigation Of the Mechanism Un-derlying Insulin Secretionmentioning

confidence: 99%

Development of Therapeutic Agents with a Novel Mechanism of Action Targeting Pancreatic β-Cells for Diabetes

Kaneko

2023

Biological & Pharmaceutical Bulletin

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“…However, diacylglycerol has also been shown to inhibit insulin release via a PKC-independent mechanism in HIT T-15 islet cells, via modulation of Ca 2+ flux [61,62]. Sawatini et al (2019) demonstrated a biphasic response to type I DGK inhibitor, R59949, in MIN6 β cells: while low concentrations of the type I DGK inhibitor, R59949, increase PKC-dependent insulin secretion, higher concentrations (>10 µM), which trigger higher levels of diacylglycerol, suppress this process, possibly via loss of voltage-dependent Ca 2+ channel activity [63,64]. Esterification of both fatty acids and diacylglycerol into the relatively inert triacylglycerol pool protect against the accumulation of bioactive (and potentially toxic lipids) (above) [53][54][55].…”

Section: Fatty Acids Diacylglycerols Triacylglycerols and Beta Cell D...mentioning

confidence: 99%

MicroRNA Sequences Modulated by Beta Cell Lipid Metabolism: Implications for Type 2 Diabetes Mellitus

Tarlton

Patterson

Graham

2021

Biology

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Alterations in lipid metabolism within beta cells and islets contributes to dysfunction and apoptosis of beta cells, leading to loss of insulin secretion and the onset of type 2 diabetes. Over the last decade, there has been an explosion of interest in understanding the landscape of gene expression which influences beta cell function, including the importance of small non-coding microRNA sequences in this context. This review sought to identify the microRNA sequences regulated by metabolic challenges in beta cells and islets, their targets, highlight their function and assess their possible relevance as biomarkers of disease progression in diabetic individuals. Predictive analysis was used to explore networks of genes targeted by these microRNA sequences, which may offer new therapeutic strategies to protect beta cell function and delay the onset of type 2 diabetes.

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“…Ca 2+ -selective fluorescent indicator, Fura-2/AM, was purchased from Abcam (ab120873), and the [Ca 2+ ] concentration was measured using dual-wavelength fluorometry as described previously [21]. The cytoplasmic cAMP levels were measured using a commercial cAMP Assay Kit (Abcam, AB65355) following the manufacturer's protocols.…”

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confidence: 99%

Pancreatic cancer-derived exosomal microRNA-19a induces β-cell dysfunction by targeting ADCY1 and EPAC2

et al. 2021

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New-onset diabetes mellitus has a rough correlation with pancreatic cancer (PaC), but the underlying mechanism remains unclear. This study aimed to explore the exosomal microRNAs and their potential role in PaC-induced β-cell dysfunction. The pancreatic β cells were treated with isolated exosomes from PaC cell lines, SW1990 and BxPC-3, before measuring the glucose-stimulated insulin secretion (GSIS), validating that SW1990 and BxPC-3 might disrupt GSIS of both β cell line MIN6 and primary mouse pancreatic islets. The difference in expression profiles between exosomes and exosome-free medium of PaC cell lines was further defined, revealing that miR-19a secreted by PaC cells might be an important signaling molecule in this process. Furthermore, adenylyl cyclase 1 (Adcy1) and exchange protein directly activated by cAMP 2 (Epac2) were verified as the direct targets of exogenous miR-19a, which was involved in insulin secretion. These results indicated that exosomes might be an important mediator in the pathogenesis of PaC-DM, and miR-19a might be the effector molecule. The findings shed light on the pathogenesis of PaC-DM.

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Dual effect of reduced type I diacylglycerol kinase activity on insulin secretion from MIN6 β-cells

Cited by 7 publications

References 36 publications

Development of Therapeutic Agents with a Novel Mechanism of Action Targeting Pancreatic β-Cells for Diabetes

Development of Therapeutic Agents with a Novel Mechanism of Action Targeting Pancreatic β-Cells for Diabetes

MicroRNA Sequences Modulated by Beta Cell Lipid Metabolism: Implications for Type 2 Diabetes Mellitus

Pancreatic cancer-derived exosomal microRNA-19a induces β-cell dysfunction by targeting ADCY1 and EPAC2

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