The principal investigator has developed a bioassay for the measurement of plasma cholecystokinin (CCK). This system employs rat pancreatic acini which respond to 1 pM CCK but react 1,000 fold weaker to gastrin. A procedure for extracting CCK from plasma allows the measurement of basal CCK levels. This assay will be used to study the physiological and pathophysiological regulation of CCK secretion in rats and humans. Studies in rats. Plasma CCK will be measured in response to intragastric instillation of fatty acids, amino acids and sugars to determine their contribution to CCK release. The effects of osmolality and volume of feedings on CCK secretion will also be assessed. Control of CCK secretion will be studied in response to cholinergic agents, adrenergic agents, bombesin and somatostatin. The existence of an enteropancreatic feedback mechanism between CCK release and pancreatic enzyme secretion will be probed by correlating plasma CCK levels with intragastric instillation of trypsin, chymotrypsin, and lipase and pancreatic enzyme inhibitors. A rat model for chronic alcoholic pancreatitis will be studied to determine whether alcohol affects CCK secretion. In addition, CCK will be extracted from plasma and rat duodenum and the molecular forms determined by gel filtration and high performance liquid chromatography. Studies in humans. The CCK response to glucose, fat, and proteins will be determined. In addition, CCK levels after feeding and CCK infusion will be correlated with the sonographic measurement of gall bladder contraction. The existence of an enteropancreatic feedback mechanism will be determined by correlating CCK release with intraluminal protease activity. CCK secretion will be evaluated in several disease states including celiac disease, irritable bowel syndrome, pancreatitis, diabetes mellitus, and cholecystectomy.
| Liddle, R A; Goldstein, R B; Saxton, J (1989) Gallstone formation during weight-reduction dieting. Arch Intern Med 149:1750-3 |
| Liddle, R A; Rushakoff, R J; Morita, E T et al. (1988) Physiological role for cholecystokinin in reducing postprandial hyperglycemia in humans. J Clin Invest 81:1675-81 |
| Geracioti Jr, T D; Liddle, R A (1988) Impaired cholecystokinin secretion in bulimia nervosa. N Engl J Med 319:683-8 |
| Liddle, R A; Carter, J D; McDonald, A R (1988) Dietary regulation of rat intestinal cholecystokinin gene expression. J Clin Invest 81:2015-9 |
| Rushakoff, R J; Goldfine, I D; Carter, J D et al. (1987) Physiological concentrations of cholecystokinin stimulate amino acid-induced insulin release in humans. J Clin Endocrinol Metab 65:395-401 |
