ISSN:
1432-0428
Schlagwort(e):
Islets of Langerhans
;
B-cell replication
;
insulin release
;
insulin biosynthesis
;
growth hormone
;
insulin-like growth factor I
;
somatomedin C
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Summary We have investigated whether the previously demonstrated stimulatory actions of growth hormone on DNA synthesis and (pro)insulin biosynthesis and release of isolated adult rat islets of Langerhans are mediated by an autocrine release of somatomedin-C/insulin-like growth factor I (SM-C/IGF I). In medium containing 1% fetal calf serum, the presence of 16.7 mmol/l glucose, or 2.7 mmol/l glucose supplemented with a concentrate of essential amino acids, caused a significant increase in 3H-thymidine incorporation and insulin release compared to 2.7 mmol/l glucose alone but no increase in SM-C/IGFI release. Further supplementation with 1 μg/ml growth hormone increased 3H-thymidine incorporation and SM-C/IGF I release within all groups, and insulin release in the 16.7 mmol/l glucose and 2.7 mmol/l plus amino acid groups. The ability of growth hormone to increase 3H-thymidine incorporation in the presence of 16.7 mmol/l glucose, but not its action on insulin release, was partly inhibited by a monoclonal antibody against SM-C/IGF I (control cultures 100%; growth hormone alone 261±27%, mean±SEM; growth hormone+anti-SM-C/IGFI 179±21%; p〈0.05, n=18). Growth hormone, but not 100 ng/ml SM-C/IGF I, increased insulin biosynthesis assessed as immunoprecipitable 3H-labelled insulin by 45%, but this was accompanied by a similar increase in overall protein synthesis. Similarly growth hormone, but not SM-C/IGF I caused a 75% increase in glucose oxidation by islets. Both growth hormone and SM-C/IGF I failed to increase the cellular uptake of α-aminoisobutyric acid or 3-O-methyl glucose over a 90 min period. The results suggest that while the stimulatory effect of growth hormone on islet cell insulin biosynthesis and release, glucose oxidation and general protein synthesis is probably direct, its action on B-cell replication is partly mediated by a paracrine release of SM-C/IGF I. This may provide a mechanism for increasing B-cell mass and consequently total insulin output during times of increased metabolic demands on insulin secretion.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00265093
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