Objective: Pancreatic b-cell dysfunction is described to be present at the diagnosis of type 2 diabetes mellitus (T2DM) and progressively deteriorated with disease duration. However, its progression is variable and potentially influenced by several factors. The Magnesium (Mg) deficiency mediates insulin resistance but reports regarding its role in pancreatic β-cell dysfunction are scarce and co...

PANDER (PANcreatic DERived factor, FAM3B), a newly discovered secreted cytokine, is specifically expressed at high levels in the islets of Langerhans of the endocrine pancreas. To evaluate the role of PANDER in beta-cell function, we investigated the effects of PANDER on rat, mouse, and human pancreatic islets; the beta-TC3 cell line; and the alpha-TC cell line. PANDER protein was present in al...

To analyze cell lineage in the pancreatic islets, we have irreversibly tagged all the progeny of cells through the activity of Cre recombinase. Adult glucagon alpha and insulin beta cells are shown to derive from cells that have never transcribed insulin or glucagon, respectively. Also, the beta-cell progenitors, but not alpha-cell progenitors, transcribe the pancreatic polypeptide (PP) gene. F...

The pancreatic elastase I gene (ELA1) is selectively transcribed to high levels in pancreatic acinar cells. Pancreatic specificity is imparted by a 100-base pair enhancer that activates transcription in beta-cells of the islets of Langerhans as well as in acinar cells. Adjacent to the enhancer is a silencer that renders transcription specific to acinar cells by selectively suppressing the inher...

OBJECTIVE Islet transplantations have been performed clinically, but their practical applications are limited. An extensive effort has been made toward the identification of pancreatic beta-cell stem cells that has yielded many insights to date, yet targeted reconstitution of beta-cell mass remains elusive. Here, we present a mouse model for inducible and reversible ablation of pancreatic beta-...

In type 2 diabetes, the beta cells of the pancreas fail to produce enough insulin to meet the body's demand, in part because of an acquired decrease in beta-cell mass. In adults, pancreatic beta-cell mass is controlled by several mechanisms, including beta-cell replication, neogenesis, hypertrophy, and survival. Here, I discuss evidence supporting the notion that increased beta-cell apoptosis i...

It is unclear whether the cellular origin of various forms of pancreatic cancer involves transformation or transdifferentiation of different target cells or whether tumors arise from common precursors, with tumor types determined by the specific genetic alterations. Previous studies suggested that pancreatic ductal carcinomas might be induced by polyoma middle T antigen (PyMT) expressed in non-...

Transforming growth factor-beta (TGF-beta) inhibits pancreatic acinar cell growth. In many cell types, TGF-beta mediates its growth inhibitory effects by activation of Smad proteins. Recently, it has been reported that Smad proteins may interact with the mitogen-activated protein (MAP) kinase signaling pathways. In this study, we report on the interactions between the TGF-beta and MAP kinase si...

Insulin replacement therapy is essential in type 1 diabetic individuals and is required in ~40- 50% of type 2 diabetics during their lifetime. Prior attempts at beta cell regeneration have relied upon pancreatic injury to induce beta cell proliferation, dedifferentiation and activation of the embryonic pathway, or stem cell replacement. We report an alternative method to transform adult non-ste...