Amino acids and human amniotic fluid increase DNA biosynthesis in pancreatic islets of adult mouse, but this effect is lost following exposure to streptozotocin.
The present study describes the effects of growth hormone (GH), amino acids, and human amniotic fluid on the function and replication of normal and SZ-treated adult mouse pancreatic islets. Thus, mouse islets were exposed in vitro to SZ or vehicle only, and maintained in culture for 7 days in RPMI 1640 containing 11.1 mM glucose and the different supplements described above. Supplementation with amino acids increased the insulin accumulation in the medium, DNA biosynthesis, and polyamine contents in the control islets. In the SZ-treated islets, amino acids increased insulin accumulation in the medium and polyamine contents, but not DNA biosynthesis. Culture of control islets in the presence of 10% human amniotic fluid increased the insulin accumulation in the medium, islet insulin content, total protein and (pro)insulin biosynthesis, and DNA biosynthesis. However, in the SZ-treated islets, the effects of human amniotic fluid were limited to an increase in insulin content and insulin accumulation in the medium. GH significantly increased insulin accumulation in the medium in control, but not SZ-treated islets. In both groups of islets, GH failed to induce a significant increase in thymidine incorporation. It is concluded that amino acids and human amniotic fluid are potent stimulators of DNA biosynthesis in adult mouse pancreatic beta cells, perhaps due to an increase in cellular polyamine contents. However, following exposure to streptozotocin, the islets are not anymore responsive to these stimulators of DNA biosynthesis.
Dunger
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Central Institute of Diabetes Gerhardt Katsch, Karlsburg, G.D.R.
Sjöholm
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Eizirik
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DL
D000596:Amino Acids / Q000494:pharmacology*; D000653:Amniotic Fluid / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D013006:Growth Hormone / Q000494:pharmacology; D007328:Insulin / Q000032:analysis / Q000378:metabolism; D007515:Islets of Langerhans / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D011073:Polyamines / Q000032:analysis; D011384:Proinsulin / Q000032:analysis / Q000096:biosynthesis; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis; D013311:Streptozocin / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D000596:Amino Acids; D007328:Insulin; D011073:Polyamines; D011506:Proteins; D013311:Streptozocin; D013006:Growth Hormone; D004247:DNA; D011384:Proinsulin; D005947:Glucose; D013936:Thymidine