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Updated: Nov 11, 2025
A High-content In Vitro Pancreatic Islet β-cell Replication Discovery Platform
Published on: July 16, 2016
Diacylglycerol kinase δ functions as a proliferation suppressor in pancreatic β-cells
Taiji Sato1, Chihiro Ishiwatari1, Yukiko K Kaneko1
1Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Abstract:
Although an aberrant reduction in pancreatic β-cell mass contributes to the pathogenesis of diabetes, the mechanism underlying the regulation of β-cell mass is poorly understood. Here, we show that diacylglycerol kinase δ (DGKδ) is a key enzyme in the regulation of β-cell mass. DGKδ expression was detected in the nucleus of β-cells. We developed β-cell-specific DGKδ knockout (βDGKδ KO) mice, which showed lower blood glucose, higher plasma insulin levels, and better glucose tolerance compared to control mice. Moreover, an increased number of small islets and Ki-67-positive islet cells, as well as elevated cyclin B1 expression in the islets, were detected in the pancreas of βDGKδ KO mice. DGKδ knockdown in the β-cell line MIN6 induced significant increases in bromodeoxyuridine (BrdU) incorporation and cyclin B1 expression. Finally, we confirmed that streptozotocin-induced hyperglycemia and β-cell loss were alleviated in βDGKδ KO mice. Thus, suppressing the expression or enzymatic activity of DGKδ that functions as a suppressor of β-cell proliferation could be a novel therapeutic approach to increase β-cell mass for the treatment of diabetes.
Insights
Diacylglycerol kinase delta (DGKδ) suppresses pancreatic beta-cell proliferation. Inhibiting DGKδ increases beta-cell mass, offering a potential new treatment for diabetes by improving glucose control.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Biology
Background:
- Reduced pancreatic beta-cell mass is a key factor in diabetes development.
- Mechanisms regulating beta-cell mass are not fully understood.
Purpose of the Study:
- To investigate the role of diacylglycerol kinase delta (DGKδ) in regulating pancreatic beta-cell mass.
- To explore DGKδ as a potential therapeutic target for diabetes.
Main Methods:
- Generated beta-cell-specific DGKδ knockout (βDGKδ KO) mice.
- Analyzed glucose tolerance, insulin levels, and islet morphology.
- Utilized MIN6 beta-cell line for knockdown studies measuring proliferation markers (BrdU, cyclin B1).
- Assessed DGKδ KO mice in a streptozotocin-induced diabetes model.
Main Results:
- βDGKδ KO mice exhibited improved glucose tolerance, lower blood glucose, and higher insulin levels.
- Increased beta-cell proliferation markers (Ki-67, cyclin B1) and smaller islets were observed in βDGKδ KO mice.
- DGKδ knockdown in MIN6 cells significantly increased proliferation (BrdU incorporation) and cyclin B1 expression.
- βDGKδ KO mice showed reduced hyperglycemia and beta-cell loss in a diabetes model.
Conclusions:
- DGKδ acts as a suppressor of beta-cell proliferation.
- Suppression of DGKδ enhances beta-cell mass and improves glucose homeostasis.
- Targeting DGKδ represents a novel therapeutic strategy for increasing beta-cell mass in diabetes treatment.
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