Pancreatic β-cell neogenesis in vivo holds great promise for cell replacement therapy diabetic patients, and discovering the relevant clinical therapeutic strategies would push it forward to application. Liraglutide, a widely used antidiabetic glucagon-like peptide-1 (GLP-1) analog, has displayed diverse β-cell-protective effects type 2 animals. Glucagon receptor (GCGR) monoclonal antibody (mAb...

Morisset, Jean, Helen Wong, John H. Walsh, J. Lainé, and Judith Bourassa. Pancreatic CCKB receptors: their potential roles in somatostatin release and d-cell proliferation. Am J Physiol Gastrointest Liver Physiol 279: G148–G156, 2000.—In rodents, cholecystokinin (CCK) induces pancreatic enzyme secretion and pancreas growth through its CCKA receptors. It is unknown whether occupation of the CCKB...

(Cell Reports 32, 108067-1–108067-13.e1–e6; August 25, 2020) In the originally published version of this article, Tables S4 and S6 contained incorrect gene labels. The corrected supplemental tables now appear with article online. authors regret error. Single-Cell Transcriptome Profiling Reveals β Cell Maturation in Stem Cell-Derived Islets after TransplantationAugsornworawat et al.Cell ReportsA...

We sought direct evidence for anti-islet cellular cytotoxicity in diabetic Bio-Breeding/Worcester (BB/W) rats by comparing the effects of splenic lymphoid cells from BB/W diabetic (D), diabetes-prone (DP), and diabetes-resistant (DR) rats on the release of 51Cr from damaged islet cells in vitro. D and DP splenic lymphoid cells were cytotoxic to major histocompatibility complex (MHC)-compatible ...

Type 2 diabetes is characterized by insulin resistance, hyperglycemia, and progressive β cell dysfunction. Excess glucose and lipid impair β cell function in islet cell lines, cultured rodent and human islets, and in vivo rodent models. Here, we examined the mechanistic consequences of glucotoxic and lipotoxic conditions on human islets in vivo and developed and/or used 3 complementary models t...

The cytoarchitecture of human islets has been examined, focusing on cellular associations that provide the anatomical framework for paracrine interactions. By using confocal microscopy and multiple immunofluorescence, we found that, contrary to descriptions of prototypical islets in textbooks and in the literature, human islets did not show anatomical subdivisions. Insulin-immunoreactive beta c...

FasL, perforin, TNFα, IL-1 and NO have been considered as effector molecule(s) leading to β-cell death in autoimmune diabetes. However, the real culprit(s) of β-cell destruction have long been elusive despite intense investigation. Previously we have suggested IFNγ/TNFα synergism as the final effector molecules in autoimmune diabetes of NOD mice. A combination of IFNγ and TNFα but neither cytok...

Recent advances in the understanding of the genetics of type 2 diabetes (T2D) susceptibility have focused attention on the regulation of transcriptional activity within the pancreatic beta-cell. MicroRNAs (miRNAs) represent an important component of regulatory control, and have proven roles in the development of human disease and control of glucose homeostasis. We set out to establish the miRNA...

OBJECTIVE Glucagon-like peptide-1 induces glucose-dependent insulin secretion and, in rodents, increases proliferation and survival of pancreatic beta cells. To investigate the effects on human beta cells, we used immunodeficient mice transplanted with human islets. The goal was to determine whether lixisenatide, a glucagon-like peptide-1 receptor agonist, improves human islet function and surv...