Growth factors and beta cell replication.
Recent studies have demonstrated that human islet allograft transplantation can be a successful therapeutic option in the treatment of patients with Type I diabetes. However, this impressive recent advance is accompanied by a very important constraint. There is a critical paucity of pancreatic islets or pancreatic beta cells for islet transplantation to become a large-scale therapeutic option in patients with diabetes. This has prompted many laboratories around the world to invigorate their efforts in finding ways for increasing the availability of beta cells or beta cell surrogates that potentially could be transplanted into patients with diabetes. The number of studies analyzing the mechanisms that govern beta cell proliferation and growth in physiological and pathological conditions has increased exponentially during the last decade. These studies exploring the role of growth factors, intracellular signaling molecules and cell cycle regulators constitute the substrate for future strategies aimed at expanding human beta cells in vitro and/or in vivo after transplantation. In this review, we describe the current knowledge on the effects of several beta cell growth factors that have been shown to increase beta cell proliferation and expand beta cell mass in vitro and/or in vivo and that they could be potentially deployed in an effort to increase the number of patients transplanted with islets. Furthermore, we also analyze in this review recent studies deciphering the relevance of these specific islet growth factors as physiological and pathophysiological regulators of beta cell proliferation and islet growth.
Vasavada
Rupangi C
RC
Division of Endocrinology, University of Pittsburgh, BST-E1140, PA 15261, USA.
Gonzalez-Pertusa
Jose A
JA
Fujinaka
Yuichi
Y
Fiaschi-Taesch
Nathalie
N
Cozar-Castellano
Irene
I
Garcia-Ocaña
Adolfo
A
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D052216:Glucagon-Like Peptide 1 / Q000502:physiology; D013006:Growth Hormone / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation; D044162:Parathyroid Hormone-Related Protein / Q000502:physiology; D010928:Placental Lactogen / Q000502:physiology; D011388:Prolactin / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013002:Somatomedins / Q000502:physiology
D006133:Growth Substances; D007328:Insulin; D044162:Parathyroid Hormone-Related Protein; D013002:Somatomedins; D017228:Hepatocyte Growth Factor; D052216:Glucagon-Like Peptide 1; D011388:Prolactin; D013006:Growth Hormone; D010928:Placental Lactogen