Noninvasive quantitative evaluation of viable islet grafts using In-exendin-4 SPECT/CT.

Islet transplantation (IT) is an effective β-cell replacement therapy for patients with type 1 diabetes; however, the lack of methods to detect islet grafts and evaluate their β-cell mass (BCM) has limited the further optimization of IT protocols. Therefore, the development of noninvasive β-cell imaging is required. In this study, we investigated the utility of the Indium-labeled exendin-4 probe {[Lys12(111In-BnDTPA-Ahx)] exendin-4} ( In exendin-4) to evaluate islet graft BCM after intraportal IT.

Preservation effect of imeglimin on pancreatic β-cell mass: Noninvasive evaluation using In-exendin-4 SPECT/CT imaging and the perspective of mitochondrial involvements.

Progressive loss of β-cell mass (BCM) has a pernicious influence on type 2 diabetes mellitus (T2DM); evaluation of BCM has conventionally required an invasive method that provides only cross-sectional data. However, a noninvasive approach to longitudinal assessment of BCM in living subjects using an indium 111-labeled exendin-4 derivative ([Lys12(In-BnDTPA-Ahx)]exendin-4) (In-exendin-4) has been developed recently. Imeglimin is a novel antidiabetic agent that is reported to improve glycemic control and glucose-stimulated insulin secretion (GSIS) augmentation of mitochondrial function.

Single-Cell Transcriptome Analysis Dissects the Replicating Process of Pancreatic Beta Cells in Partial Pancreatectomy Model.

Heterogeneity of gene expression and rarity of replication hamper molecular analysis of β-cell mass restoration in adult pancreas. Here, we show transcriptional dynamics in β-cell replication process by single-cell RNA sequencing of murine pancreas with or without partial pancreatectomy. We observed heterogeneity of -expressing β-cells and identified the one cluster as replicating β-cells with high expression of cell proliferation markers and .

Generation and Characterization of a Novel Mouse Model That Allows Spatiotemporal Quantification of Pancreatic β-Cell Proliferation.

Pancreatic β-cell proliferation has been gaining much attention as a therapeutic target for the prevention and treatment of diabetes. In order to evaluate potential β-cell mitogens, accurate and reliable methods for the detection and quantification of the β-cell proliferation rate are indispensable. In this study, we developed a novel tool that specifically labels replicating β-cells as mVenus cells by using RIP-Cre; R26Fucci2aR mice expressing the fluorescent ubiquitination-based cell cycle indicator Fucci2a in β-cells.

GPR40 activation initiates store-operated Ca entry and potentiates insulin secretion via the IP3R1/STIM1/Orai1 pathway in pancreatic β-cells.

The long-chain fatty acid receptor GPR40 plays an important role in potentiation of glucose-induced insulin secretion (GIIS) from pancreatic β-cells. Previous studies demonstrated that GPR40 activation enhances Ca release from the endoplasmic reticulum (ER) by activating inositol 1,4,5-triphosphate (IP3) receptors. However, it remains unknown how ER Ca release via the IP3 receptor is linked to GIIS potentiation.