TY - JOUR
T1 - Hormonal regulation of amino acid accumulation in human fetal liver explants Effects of dibutyryl cyclic AMP, glucagon and insulin
AU - Schwartz, Alan
N1 - Funding Information:
The authorw ishest o acknowledgteh ec riticismo f ProfessoTr .W. Rall and the generougs ift of insulin from Dr J. SchlichtkrullN, ovo ResearchIn stitute. This study was in part supportedb y grantst o Dr N.C.R. R~iih~fri omthe Sigrid Juselius Stifelste, Helsinki and by the U.S. Public Health Service Grant GM-00661-11/12to the Departmenotf PharmacologyC,W RU, and the National FoundationN, ew York.
PY - 1974/9/5
Y1 - 1974/9/5
N2 - α-Aminoisobutyrate accumulation by human fetal liver explants in organ culture is stimulated by dibutyryl cyclic AMP (N6, 2′O-dibutyryl adenosine 3′-5′: cyclic monophosphate), glucagon or insulin. Theophylline increased the effect of submaximal concentrations of dibutyryl cyclic AMP or glucagon. Maximal concentrations of glucagon and dibutyryl cyclic AMP yielded the same results as either agent alone. A period of about 4-6 h was required to observe the stimulatory effect of dibutyryl cyclic AMP or insulin, which could be completely prevented by simultaneous incubation with cycloheximide. Maximal effects of either dibutyryl cyclic AMP or glucagon plus insulin produced additive results. These data support the hypothesis that insulin acts via a mechanism independent of the glucagon-cyclic AMP pathway in liver tissue. In addition, the pharmacologic receptor for glucagon was detected in liver explants from a 30-mm (crown - rump) specimen (6 weeks gestation). The liver had the competence to respond to dibutyryl cyclic AMP by the 36-mm stage. Tissue from a 36-mm specimen did not respond to insulin, but a clear response was elicited from a specimen at the 48-mm stage. These data demonstrate the ability of human fetal liver to respond to hormones at a very early stage in gestation.
AB - α-Aminoisobutyrate accumulation by human fetal liver explants in organ culture is stimulated by dibutyryl cyclic AMP (N6, 2′O-dibutyryl adenosine 3′-5′: cyclic monophosphate), glucagon or insulin. Theophylline increased the effect of submaximal concentrations of dibutyryl cyclic AMP or glucagon. Maximal concentrations of glucagon and dibutyryl cyclic AMP yielded the same results as either agent alone. A period of about 4-6 h was required to observe the stimulatory effect of dibutyryl cyclic AMP or insulin, which could be completely prevented by simultaneous incubation with cycloheximide. Maximal effects of either dibutyryl cyclic AMP or glucagon plus insulin produced additive results. These data support the hypothesis that insulin acts via a mechanism independent of the glucagon-cyclic AMP pathway in liver tissue. In addition, the pharmacologic receptor for glucagon was detected in liver explants from a 30-mm (crown - rump) specimen (6 weeks gestation). The liver had the competence to respond to dibutyryl cyclic AMP by the 36-mm stage. Tissue from a 36-mm specimen did not respond to insulin, but a clear response was elicited from a specimen at the 48-mm stage. These data demonstrate the ability of human fetal liver to respond to hormones at a very early stage in gestation.
UR - http://www.scopus.com/inward/record.url?scp=0016263234&partnerID=8YFLogxK
U2 - 10.1016/0304-4165(74)90220-7
DO - 10.1016/0304-4165(74)90220-7
M3 - Article
C2 - 4371400
AN - SCOPUS:0016263234
SN - 0304-4165
VL - 362
SP - 276
EP - 289
JO - BBA - General Subjects
JF - BBA - General Subjects
IS - 2
ER -