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Physiological Concentrations of Cholecystokinin Stimulate Amino Acid-Induced Insulin Release in Humans^*

Cell Biology Laboratory and the Department of Medicine, Mount Zion Hospital and Medical Center San Francisco, California 94120
The Departments of Medicine and Physiology, University of California San Francisco, California 94143

Address all correspondence and requests for reprints to: Rodger A. Liddle, M.D., Cell Biology Laboratory, Mount Zion Hospital and Medical Center, P.O. Box 7921, San Francisco, California 94120.

After a meal, hormones released from the gut potentiate insulin release. This study was undertaken to determine if physiological concentrations of plasma cholecystokinin (CCK) stimulate insulin secretion in man. Employing a specific CCK bioassay, postprandial CCK levels were determined in normal subjects. Ingestion of a mixed liquid meal stimulated an increase in circulating CCK from a mean fasting level of 0.9 ± 0.2 (SEM) pmol/L to a mean peak level of 7.1 ± 1.1 pmol/L within 10 min of feeding. After 30 min the mean CCK level fell o t 3.5 pmol/JL, and remained elevated for the remainder of the 90-min experiment. Eight subjects underwent 40-min infusions of either arginine (15 g), mixed amino acids (15 g), or glucose (30 g) with or without the simultaneous infusion of CCK-8. Since CCK-8 has full biological potency, this form was chosen for infusion to reproduce total CCK bioactivity in plasma. CCK-8 was infused at rates of 12 or 24 pmol/kgh, producing steady state plasmq CCK levels of 4.5 ± 0.7 and 8.2 ± 1.1 pmol/L, respectively, spanning the range of normal postprandial levels. CCK alone had no effect on insulin, glucose, or glucagon levels. Administration of arginirte alone stimulated insulin from a mean basal level of 12.8 ± 1.3 µU/mL to a peak level of 41.3 ± 5.4 µU/mL. Infusion of CCK at 12 and 24 pmol/kg·h augmented arginine-stimulated insulin levels to peaks of 62.5 ± 13.9 and 63.0 ± 4.0 µU/mL, respectively. Moreover, CCK nearly doubled the total amount of insulin secreted during the arginine infusion. A similar potentiation of glucagon release was found with both doses of CCK. In addition, infusion of a mixture of amino acids with and without concomitant CCK infusions revealed that CCK potentiated the insulin release induced by mixed amino acids. In contrast to the potent effect of CCK on amino acid-induced insulin release, infusions of CCK together with glucose caused no enhancement of glucose-stimulated insulin release. These results demonstrate that physiological concentrations of CCK potentiate amino acid (but not glucose)-induced insulin secretion in man. These data suggest, therefore, that CCK may have a role in man as a modulator of insulin release. (J Clin Endocrinol Mefab 65: 395, 1987)

^* Presented in part at the annual meeting of the American Diabetes Association, June 23,1986, and has appeared in abstract form (Diabetes 35:181 [Suppl 1], 1986).

This work was supported by NIH Training Grant AM-07997-11 (to R.J.R.), USPHS Grants DK-32994 and DK-01291, and grants from the Academic Senate and Research Evaluation and Allocation Committee of the University of California.

Received November 24, 1986.

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