Expression of insulin-like growth factors (IGFs) and their binding proteins (IGF BPs) during pancreatic development in rat, and modulation of IGF actions on rat islet DNA synthesis by IGF BPs.
Growth of pancreatic beta-cells is an essential feature of development in order to maintain insulin availability. While glucose has been shown to increase beta-cell DNA synthetic rate in cultures of isolated islets of Langerhans, there is also evidence for a local control of beta-cell growth involving insulin-like growth factors (IGFs). IGF I and II and their specific binding proteins (IGF BPs) are expressed within the developing rat pancreas, and released by isolated fetal rat islets of Langerhans. Glucose-induced beta-cell growth is not mediated by IGF-I, since IGF release does not alter in response to changes in glucose availability. In contrast, IGF BP release is positively associated with glucose concentrations over the physiological range and is therefore a candidate. Exogenous hIGF BP1 or bIGF BP2 synergistically interacted with hIGF I or II to increase DNA synthesis within isolated fetal rat islets. These results suggest a role for IGF BPs in the regulation of beta-cell growth. They may act independently or by modulation of IGF bioavailability during pancreatic development.
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000494:pharmacology; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D005786:Gene Expression Regulation; D005865:Gestational Age; D005947:Glucose / Q000494:pharmacology; D018970:Insulin-Like Growth Factor Binding Protein 1; D007515:Islets of Langerhans / Q000187:drug effects / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D013002:Somatomedins / Q000096:biosynthesis* / Q000494:pharmacology
D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D012333:RNA, Messenger; D013002:Somatomedins; D005947:Glucose