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Research Article Free access | 10.1172/JCI107538

Effect of Glucagon on Net Splanchnic Cyclic AMP Production in Normal and Diabetic Men

John E. Liljenquist, James D. Bomboy, Stephen B. Lewis, Bruce C. Sinclair-Smith, Philip W. Felts, William W. Lacy, Oscar B. Crofford, and Grant W. Liddle

Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Department of Physiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Veterans Administration Hospital, Nashville, Tennessee 37232

Find articles by Liljenquist, J. in: PubMed | Google Scholar

Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Department of Physiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Veterans Administration Hospital, Nashville, Tennessee 37232

Find articles by Bomboy, J. in: PubMed | Google Scholar

Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Department of Physiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Veterans Administration Hospital, Nashville, Tennessee 37232

Find articles by Lewis, S. in: PubMed | Google Scholar

Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Department of Physiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Veterans Administration Hospital, Nashville, Tennessee 37232

Find articles by Sinclair-Smith, B. in: PubMed | Google Scholar

Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Department of Physiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Veterans Administration Hospital, Nashville, Tennessee 37232

Find articles by Felts, P. in: PubMed | Google Scholar

Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Department of Physiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Veterans Administration Hospital, Nashville, Tennessee 37232

Find articles by Lacy, W. in: PubMed | Google Scholar

Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Department of Physiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Veterans Administration Hospital, Nashville, Tennessee 37232

Find articles by Crofford, O. in: PubMed | Google Scholar

Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Department of Physiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Veterans Administration Hospital, Nashville, Tennessee 37232

Find articles by Liddle, G. in: PubMed | Google Scholar

Published January 1, 1974 - More info

Published in Volume 53, Issue 1 on January 1, 1974
J Clin Invest. 1974;53(1):198–204. https://doi.org/10.1172/JCI107538.
© 1974 The American Society for Clinical Investigation
Published January 1, 1974 - Version history
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Abstract

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.

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