Interleukin 1 dose-dependently affects the biosynthesis of (pro)insulin in isolated rat islets of Langerhans.
Human crude and recombinant interleukin 1 (IL-1) was found to dose- and time-dependently affect the biosynthesis of (pro)insulin in isolated rat islets of Langerhans. Incubation of rat islets with either 0.5 U/ml or 5 U/ml of crude IL-1 for 1 h had no detectable effect on (pro)insulin biosynthesis. After 24 hours of exposure 0.5 U/ml of crude or 0.6 ng/ml of recombinant IL-1 (beta) increased the (pro)insulin biosynthesis by 42% and 58%, respectively, whereas a 10-fold greater concentration of IL-1 decreased the (pro)insulin biosynthesis by 74% and 89%, respectively. The increase in (pro)insulin biosynthesis was accompanied by an increase in total protein biosynthesis indicating a nonspecific stimulatory action of low IL-1 concentrations. In contrast, high IL-1 concentrations caused a more selective decrease of the (pro) insulin biosynthesis when compared to the total protein biosynthesis. In addition, low IL-1 concentrations were found to increase and high concentrations to decrease the relative levels of pre-proinsulin mRNA suggesting that IL-1 may act both at a pre- and post-translational level of insulin biosynthesis.
Spinas
G A
GA
Steno Memorial Hospital, Gentofte, Denmark.
Hansen
B S
BS
Linde
S
S
Kastern
W
W
Mølvig
J
J
Mandrup-Poulsen
T
T
Dinarello
C A
CA
Nielsen
J H
JH
Nerup
J
J
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D066298:In Vitro Techniques; D007328:Insulin; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D011384:Proinsulin / Q000096:biosynthesis* / Q000235:genetics; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D007375:Interleukin-1; D011498:Protein Precursors; D012333:RNA, Messenger; C013737:preproinsulin; D011384:Proinsulin