Abstract
The present study was undertaken to investigate postprandial responses of cholecystokinin (CCK) and pancreatic polypeptide (PP) and their interrelationship in patients with diabetes mellitus (DM) with and without autonomic neuropathy (AN). Twenty-two patients with DM (seven with AN and 15 without AN) and 14 age-matched healthy controls were studied. AN was diagnosed according to several tests of cardiovascular autonomic function. CCK and PP plasma levels were measured by specific radioimmunoassays before and at several time points after the oral administration of a test meal. Basal CCK plasma levels in DM patients were normal, whereas basal PP plasma levels were increased (139±18 vs 72±7 pg/ml;P<0.01). Integrated postprandial CCK response was increased in DM patients (208±27 vs 110±14 pmol/liter/2 hr;P<0.05), mainly due to the patients with AN. Postprandial PP response was increased in DM patients without AN (37,273±5241 vs 13,418±3299 pg/ml/2 hr;P<0.001) but not in those with AN (8887±3461 pg/ml/2 hr). Moreover, PP response was closely (P<0.002) correlated with the degree of AN. A direct and linear correlation between postprandial CCK and PP responses was found in healthy controls (r=0.78;P<0.005) but not in DM patients. We conclude that the CCK response to a meal is increased in diabetic patients with AN, whereas the PP response is increased only with an intact autonomic nervous system. It is suggested that the correlation between postprandial hormonal responses in healthy subjects is due to the potency of CCK as PP releasing agent and that this interaction does not work in diabetic patients.
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Cantor P: Cholecystokinin in plasma. Digestion 42:181–201, 1989
Becker HD, Werner M, Schafmayer A: Release of radioimmunologic cholecystokinin in human subjects. Am J Surg 147:124–128, 1984
Hopman WPM, Jansen JBMJ, Lamers CBHW: Plasma cholecystokinin response to a liquid fat meal in vagotomized patients. Ann Surg 200:693–697, 1984
Hopman WPM, Jansen JBMJ, Lamers CBHW: Effect of atropine on the plasma cholecystokinin response to intraduodenal fat in man. Digestion 29:19–25, 1984
Maton PN, Selden AC, Chadwick VS: Atropine inhibits meal-stimulated release of cholecystokinin. Scand J Gastroenterol 19:831–834, 1984
Schwartz TW, Rehfeld JF, Stadil F, Larsson LI, Moon N, Chance RE: Pancreatic polypeptide response to food in duodenal ulcer patients before and after truncal vagotomy. Lancet 1:1102–1105, 1976
Taylor IL, Impicciatore M, Walsh JH: Effect of atropine and vagotomy on the pancreatic polypeptide response to a meal. Am J Physiol 235:E443-E447, 1978
Schwartz TW: Pancreatic polypeptide: A hormone under vagal control. Gastroenterology 85:1411–1425, 1983
Adler G, Beglinger C, Braun U, Reinshagen M, Koop I, Schafmayer A: Cholecystokinin is a regulator of intestinal phase-stimulated PP release. Regul Pept 30:105–111, 1990
Meier R, Hildebrand P, Thumshirn M, Albrecht C, Studer B, Gyr K, Beglinger C: Effect of loxiglumide, a cholecystokinin antagonist, on pancreatic polypeptide release in humans. Gastroenterology 99:1757–1762, 1990
Lugari R, Gnudi A, Dall'Argine P, Vattini A, Rignanese G, Dall'Aglio B, Melchionda N, Colella P, Luciani A, Toscani S, Zandomeneghi R: Diabetic autonomic neuropathy and impaired human pancreatic polypeptide secretion in response to food. J Clin Endocrinol Metab 64:279–282, 1987
Hossdorf T, Wagner M, Hoppe HW: Pancreatic polypeptide (PP) response to food in type I diabetics with and without diabetic autonomic neuropathy. Hepatogastroenterology 35:238–241, 1988
Floyd JC: Pancreatic polypeptide. Clin Gastroenterol 9:657–678, 1980
Nakano I, Funakoshi A, Shinozaki H, Miyazaki K, Ibayashi H, Tateishi K, Hamaoka T: High plasma cholecystokinin response following ingestion of test meal by patients with non-insulin dependent diabetes mellitus. Regul Pept 14:229–236, 1986
Mitsukawa T, Takemura J, Ohgo S, Mizuta M, Ii T, Kuribayashi T, Matsukura S: Gallbladder function and plasma cholecystokinin levels in diabetes mellitus. Am J Gastroenterol 85:981–985, 1990
Levin AB: A simple test of cardiac function based upon the heart rate changes induced by the Valsalva manoevre. Am J Cardiol 18:90–99, 1966
Ewing DJ, Campbell JW, Murray A, Neilson JM, Clarke BJ: Immediate heart response to standing: a simple test for autonomic neuropathy in diabetes. Br Med J 1:145–147, 1978
Sundkvist G, Almer LO, Lilja B: Respiratory influence on heart rate in diabetes mellitus. Br Med J 1:924–925, 1979
Cicmir IJ, Grüneklee D, Morquet A, Berger H, Kley HK, Lehmacher W, Gries FA: Studies of heart rate oscillations in diabetics at rest. Horm Metab Res 9(suppl):73–76, 1980
Ewing DJ, Clarke BF: Diagnosis and management of diabetic autonomic neuropathy. Br Med J 285:916–918, 1982
Riepl RL, Fiedler F, Ernstberger M, Lehnert P: Effect of Na-taurodeoxycholate and phenylalanine on ecbolic pancreatic secretion and on plasma cholecystokinin in man. Eur J Clin Invest 22:A22, 1992
Taylor IL: RIA of the pancreatic polypeptide family. J Clin Immunol 10:43–49, 1987
Lonovics J, Guzman S, Devitt P, Hejtmancik KE, Suddith RL, Rayford PL, Thompson IC: Release of pancreatic polypeptide in humans by infusion of cholecystokinin. Gastroenterology 79:817–822, 1980
Beglinger C, Meyer F, Häcki W, Gyr K: The release of pancreatic polypeptide by exogenous CCK in man and dog. Digestion 22:225–228, 1981
Krarup T, Schwartz TW, Hilsted J, Madsbad S, Verlaege O, Sestoft L: Impaired response of pancreatic polypeptide to hypoglycemia: an early sign of autonomic neuropathy in diabetics. Br Med J 15:1544–1546, 1979
Levitt NS, Vinik AI, Sive AA, Van Tonder S, Lund A: Impaired pancreatic polypeptide responses to insulin induced hypoglycemia in diabetic autonomic neuropathy. J Clin Endocrinol Metab 50:445–449, 1980
Polinsky RJ, Taylor IL, Chen P, Weise V, Kopin IJ: Pancreatic polypeptide responses to hypoglycemia in chronic autonomic failure. J Clin Endocrinol Metab 54:48–52, 1982
Marco J, Hedo JA, Villanueva ML: Control of pancreatic polypeptide secretion by glucose in man. J Clin Endocrinol Metab 46:140–145, 1978
Sive AA, Vinik AI, Van Tonder S: Pancreatic polypeptide (PP) response to oral and intravenous glucose in man. Am J Gastroenterol 71:183–185, 1979
Marco J, Hedo JA, Castillo-Olivares J, Villanueva ML: Human pancreatic polypeptide secretion in conditions of exogenous and endogenous hyperglycemia. Diabetologia 19:418–422, 1980
Kostic N, Zamaklar M, Novakovic R, Popovic S: The serum levels of gastrin, somatostatin, VIP and PP in diabetics with autonomic neuropathy. Eur J Endocrinol 130(suppl 2):157, 1994
Oster-Jorgensen E, Hilsted L, Thye-Ronn P, Qvist N: Post-prandial gallbladder emptying in diabetics related to gastric emptying rate and pancreatic polypeptide. Eur J Endocrinol 130(suppl 2):157, 1994
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Glasbrenner, B., Dominguez-Munoz, E., Riepl, R.L. et al. Cholecystokinin and pancreatic polypeptide release in diabetic patients with and without autonomic neuropathy. Digest Dis Sci 40, 406–411 (1995). https://doi.org/10.1007/BF02065429
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DOI: https://doi.org/10.1007/BF02065429