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Glucagon activates hepatic adenylate cyclase, thereby increasing acutely the liver content of cyclic AMP (cAMP) as well as the release of cAMP into the hepatic vein. Insulin, on the other hand, antagonizes this glucagon-mediated cAMP production, thus providing a hypothetical mechanism through which insulin might correct some of the metabolic abnormalities of diabetes. To study this hormonal interaction in man, net splanchnic cAMP production (NScAMPP) was investigated in normal and insulin-dependent diabetic men under basal conditions and in response to intravenous glucagon, 50 ng/kg/min for 2 h. In normals (n=19), basal hepatic vein cAMP concentration was 23.6+/-1.1 nM and NScAMPP was 1.7+/-0.6 nmol/min. Glucagon stimulated NScAMPP in four normal subjects to a peak of 99.6+/-43 nmol/min at 25 min with a subsequent fall to 12.4+/-5.1 nmol/min by 90 min despite continuing glucagon infusion. Endogenous insulin secretion was stimulated as indicated by rising levels of immunoreactive insulin and C-peptide (connecting peptide) immunoreactivity, raising the possibility that endogenous insulin might be responsible for the fall in NScAMPP that followed the initial spike. In the diabetics (n=8), basal hepatic vein cAMP concentration was 24.7+/-1.2 nM and NScAMPP was undetectable. Glucagon stimulated NScAMPP in five diabetics to a peak of 169.9+/-42.6 with a subsequent fall to 17.4+/-3.9 nmol/min by 90 min even though endogenous insulin secretion was not stimulated (no rise in C-peptide immunoreactivity). Although the mean increase in NScAMPP was greater in the diabetics, the two groups did not differ significantly.Conclusions. In normal resting man the liver is a significant source of circulating cAMP. Diabetics do not release abnormally large amounts of hepatic cAMP under basal conditions. Glucagon markedly enhances hepatic cAMP release with a spike-decline pattern in both normal and diabetic men. The decline in hepatic cAMP release despite continuing glucagon stimulation is due to factors other than a stimulation of insulin secretion.
J E Liljenquist, and
J D Bomboy, and
S B Lewis, and
B C Sinclair-Smith, and
P W Felts, and
W W Lacy, and
O B Crofford, and
G W Liddle
May 1979,
Acta physiologica Scandinavica,
J E Liljenquist, and
J D Bomboy, and
S B Lewis, and
B C Sinclair-Smith, and
P W Felts, and
W W Lacy, and
O B Crofford, and
G W Liddle
March 1974,
Biochimica et biophysica acta,
J E Liljenquist, and
J D Bomboy, and
S B Lewis, and
B C Sinclair-Smith, and
P W Felts, and
W W Lacy, and
O B Crofford, and
G W Liddle
November 1974,
Acta pharmacologica et toxicologica,
J E Liljenquist, and
J D Bomboy, and
S B Lewis, and
B C Sinclair-Smith, and
P W Felts, and
W W Lacy, and
O B Crofford, and
G W Liddle
January 1979,
Biochimica et biophysica acta,
J E Liljenquist, and
J D Bomboy, and
S B Lewis, and
B C Sinclair-Smith, and
P W Felts, and
W W Lacy, and
O B Crofford, and
G W Liddle
January 1982,
Dermatologica,
J E Liljenquist, and
J D Bomboy, and
S B Lewis, and
B C Sinclair-Smith, and
P W Felts, and
W W Lacy, and
O B Crofford, and
G W Liddle
August 1977,
Acta endocrinologica,
J E Liljenquist, and
J D Bomboy, and
S B Lewis, and
B C Sinclair-Smith, and
P W Felts, and
W W Lacy, and
O B Crofford, and
G W Liddle
November 1950,
The Journal of clinical investigation,
J E Liljenquist, and
J D Bomboy, and
S B Lewis, and
B C Sinclair-Smith, and
P W Felts, and
W W Lacy, and
O B Crofford, and
G W Liddle
January 1997,
Journal of endocrinological investigation,
J E Liljenquist, and
J D Bomboy, and
S B Lewis, and
B C Sinclair-Smith, and
P W Felts, and
W W Lacy, and
O B Crofford, and
G W Liddle
February 2013,
Nature,
J E Liljenquist, and
J D Bomboy, and
S B Lewis, and
B C Sinclair-Smith, and
P W Felts, and
W W Lacy, and
O B Crofford, and
G W Liddle
January 1978,
Acta physiologica latino americana,
