Abstract: Engineered pancreatic islet organoids encoding a polypeptide not endogenously expressed in pancreatic islet cells and methods for using them to treat diseases and disorders associated with reduced or absent expression of the polypeptide are provided.

Abstract: Insulin resistance is a central feature of type II diabetes and other diseases, and may affect every tissue of the body, including the pancreatic beta cell. Insulin signaling is mediated by a complex network of diverging and converging pathways, with alternative proteins and isoforms at almost every step in the process. We have previously shown that insulin activates the transcription of its own gene by signaling through Insulin Receptor A type (Ex11?), PI3 kinase and p70 s6 kinase. When studying the mechanisms underlying the glucose-stimulated activation of the glucokinase gene in pancreatic beta cells, we now demonstrate that also here secreted insulin is a key-factor. In contrast to the insulin gene, transcription of the glucokinase gene is promoted by signaling via Insulin Receptor B type (Ex11+) and protein kinase B (c-Akt).

Abstract: Insulin resistance is a central feature of type II diabetes and other diseases, and may affect every tissue of the body, including the pancreatic beta cell. Insulin signaling is mediated by a complex network of diverging and converging pathways, with alternative proteins and isoforms at almost every step in the process. We have previously shown that insulin activates the transcription of its own gene by signaling through Insulin Receptor A type (Ex11?), PI3 kinase and p70 s6 kinase. When studying the mechanisms underlying the glucose-stimulated activation of the glucokinase gene in pancreatic beta cells, we now demonstrate that also here secreted insulin is a key-factor. In contrast to the insulin gene, transcription of the glucokinase gene is promoted by signaling via Insulin Receptor B type (Ex11+) and protein kinase B (c-Akt).

Abstract: Insulin resistance is a central feature of type II diabetes and other diseases, and may affect every tissue of the body, including the pancreatic beta cell. Insulin signaling is mediated by a complex network of diverging and converging pathways, with alternative proteins and isoforms at almost every step in the process. We have previously shown that insulin activates the transcription of its own gene by signaling through Insulin Receptor A type (Ex11−), PI3 kinase and p70 s6 kinase. When studying the mechanisms underlying the glucose-stimulated activation of the glucokinase gene in pancreatic beta cells, we now demonstrate that also here secreted insulin is a key-factor. In contrast to the insulin gene, transcription of the glucokinase gene is promoted by signaling via Insulin Receptor B type (Ex11+) and protein kinase B (c-Akt).