Horm Metab Res 2005; 37(5): 326-330
DOI: 10.1055/s-2005-861478
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Secretin-stimulated Amylase Release into Blood is Impaired in Type 1 Diabetes Mellitus

A.  Swislocki1 , R.  Noth1 , A.  Hallstone1 , E.  Kyger1 , G.  Triadafilopoulos1
  • 1 Sections of Endocrinology and Gastroenterology, Medical Service, Veterans Affairs Medical Center, Martinez, California, and Department of Internal Medicine, School of Medicine, University of California, Davis, California
Further Information

Publication History

Received 1 June 2004

Accepted after revision 25 November 2004

Publication Date:
22 June 2005 (online)

Abstract

Background: Prior studies have provided data indicating the existence of close interaction between pancreatic endocrine and exocrine function, but few clinical studies have explored this relationship in depth. We compared pancreatic exocrine function non-endoscopically in individuals with type 1 diabetes mellitus, type 2 diabetes mellitus, and normal glucose tolerant controls, to assess the importance of local insulin production to pancreatic exocrine function. Methods: The plasma amylase response to intravenous secretin challenge was measured in men with type 1 diabetes mellitus (n = 5), type 2 diabetes mellitus (n = 5), and normal controls (n = 3). Patients were characterized by their urinary excretion of c-peptide and albumin over 24 hours. Autonomic neuropathy was non-invasively assessed by measuring RR variation (with deep respiration on EKG). Results: Post-secretin amylase responses were generally absent with low baseline levels in the patients with type 1 diabetes mellitus. Patients with type 2 diabetes mellitus and controls showed similar twofold increases over baseline after secretin administration. When normal glucose tolerant and type 2 diabetic patients were pooled and compared against type 1 diabetes mellitus, the differences were statistically significant (p < 0.03). Total amylase response correlated positively, but weakly, with 24 h urinary C-peptide excretion (r = 0.507; p < 0.112), but not with glycemic control, duration of diabetes, or indices of autonomic neuropathy. Conclusions: Patients with type 1 diabetes mellitus, but not type 2 diabetes mellitus, have reduced pancreatic exocrine function, supporting the concept of a local paracrine effect of insulin on pancreatic acinar cells. Further studies are needed to determine the clinical impact of this deficiency, and whether such patients with type 1 diabetes mellitus would benefit from therapy with pancreatic enzyme supplementation.

References

  • 1 Jarotzky A J. Uber die Veranderungen in der Grosse und in Bau der Pankreaszellen mit einigen Arten der Inanition.  Virchow's Arch Patho Anat. 1899;  156 409-429
  • 2 Williams J, Goldfine I. The insulin-pancreatic acinar axis.  Diabetes. 1985;  34 980-986
  • 3 Lohr M, Kloppel G. Residual insulin positivity and pancreatic atrophy in relation to duration of chronic type 1 (insulin-dependent) diabetes mellitus and microangiopathy.  Diabetologia. 1987;  30 757-762
  • 4 Nakanishi K, Kobayashi T, Miyashita H. et al . Relationships among residual β-cells, exocrine pancreas, and islet cell antibodies in insulin-dependent diabetes mellitus.  Metabolism. 1993;  42 196-203
  • 5 Nakanishi K, Kobayashi T, Miyashita H. et al . Exocrine pancreatic ductograms in insulin-dependent diabetes mellitus.  Am J Gastroenterol. 1994;  89 762-766
  • 6 Frier B M, Faber O K, Binder C, Elliott H L. The effect of residual insulin secretion on exocrine pancreatic function in juvenile-onset diabetes mellitus.  Diabetologia. 1978;  14 301-304
  • 7 Lankisch P G, Manthey G, Otto J. et al . Exocrine pancreatic function in insulin-dependent diabetes mellitus.  Digestion. 1982;  25 211-216
  • 8 Frier B M, Adrian T E, Saunders J HB, Bloom S R. Serum trypsin concentration and pancreatic trypsin secretion in insulin-dependent diabetes mellitus.  Clinica Chimica Acta. 1980;  105 297-300
  • 9 Frier B M, Saunders J HB, Wormsley K G, Bouchier I AD. Exocrine pancreatic function in juvenile-onset diabetes mellitus.  Gut. 1976;  17 685-691
  • 10 El Newihi H, Dooley C P, Saad C, Staples J, Zeidler A, Valenzuela J E. Impaired exocrine pancreatic function in diabetics with diarrhea and peripheral neuropathy.  Dig Dis Sci. 1988;  33 705-710
  • 11 Landin-Olsson M, Borgstrom A, Blom L, Sundkvist G, Lernmark A. The Swedish Childhood Diabetes Group: Immunoreactive trypsin(ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls.  Pancreas. 1990;  5 241-247
  • 12 Lorini R, Cortona L, Scotta M S, Melzi d'Eril G V, Severi F. Exocrine pancreatic function in children and adolescents with insulin-dependent diabetes mellitus.  Diab Res Clin Pract. 1990;  8 263-267
  • 13 Yajnik C S, Sahasrabudhe R A, Naik S S. et al . Exocrine pancreatic function (serum immunoreactive trypsin, fecal chymotrypsin, and pancreatic isoamylase) in Indian diabetics.  Pancreas. 1990;  5 631-638
  • 14 Dandona P, Elias E, Beckett A G. Serum trypsin concentrations in diabetes mellitus.  Brit Med J. 1978;  2 1125
  • 15 Moffat A, Marks V, Gamble D R. Serum immunoreactive trypsin concentrations in diabetic children.  J Clin Pathol. 1980;  33 871-875
  • 16 Moller-Petersen J, Kjaergard J J, Mourits-Andersen H T, Svendsen K N, Dideriksen K, Ditzel J. Serum concentration of cathodic trypsin-like immunoreactivity and pancreatic isoamylase in insulin-dependent diabetes mellitus.  Acta Med Scand. 1982;  211 459-462
  • 17 Adrian T E, Barnes A J, Bloom S R. Hypotrypsinaemia in diabetes mellitus.  Clin Chim Acta. 1979;  97 213-216
  • 18 Moles K W, Kerr J I, Armstrong E, Hayes J R, Buchanan K D. Serum concentrations of trypsin-like immunoreactivity and pancreatic isoamylase in insulin dependent diabetic patients.  Pancreas. 1988;  3 135-139
  • 19 Foo Y, Rosalki S B, Ramdial L, Mikhailidis D, Dandona P. Serum isoamylase activities in diabetes mellitus.  J Clin Pathol. 1980;  33 1102-1105
  • 20 Junglee D, de Albarran R, Katrak A, Freedman D B, Beckett A G, Dandona P. Low pancreatic lipase in insulin-dependent diabetics.  J Clin Pathol. 1983;  36 200-202
  • 21 National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and the categories of glucose intolerance.  Diabetes. 1979;  28 1039-1057
  • 22 de Fronzo R A. The triumvirate: beta-cell, muscle, liver. A collusion responsible for non-insulin-dependent diabetes mellitus.  Diabetes. 1988;  37 667-687
  • 23 Brannon P M, Hirschi K, Korc M. Effects of epidermal growth factor, insulin, and insulin-like growth factor 1 on rat pancreatic acinar cells cultured in serum-free medium.  Pancreas. 1988;  3 41-48
  • 24 MacGregor I L, DeVeney C, Way L W, Meyer J H. The effect of acute hyperglycemia on meal-stimulated gastric, biliary, and pancreatic secretion and serum gastrin.  Gastroenterology. 1976;  70 197-202
  • 25 Unger R M, Grundy S. Hyperglycemia as an inducer as well as a consequence of impaired islet-cell function and insulin resistance: implications for the management of diabetes.  Diabetologia. 1985;  28 119-121
  • 26 Arky R A. Diet and diabetes. In: Rifkin H, Raskin P (eds) Diabetes Mellitus, volume 5. Bowie, Maryland; Robert J. Brady Co 1981
  • 27 Dubick M A, Conteas C N, Billy H T, Majumdar A PN, Geokas M C. Raised serum concentrations of pancreatic enzymes in cigarette smokers.  Gut. 1987;  28 330-335
  • 28 Florholmen J, Burhol P G, Jorde R, Waldum H L. The effect of graded doses of secretin on serum trypsin, serum pancreatic amylase, serum insulin, plasma somatostatin, and plasma pancreatic polypeptide in man.  Scand J Gastroenterol. 1984;  19 24-30
  • 29 Adler G, Bedlinger C. Hormones as regulators of pancreatic secretion in man.  Eur J Clin Invest. 1990;  20 (suppl 1) S27-S32
  • 30 Ceska M, Birath K, Brown B. A new and rapid method for the clinical determination of alpha-amylase activities in human serum and urine. Optimal conditions.  Clin Chim Acta. 1969;  26 437-444
  • 31 Ceska M, Hultman E, Ingelman B G. A new method for determination of alpha-amylase.  Experientia. 1969;  25 555-556
  • 32 Ceska M, Brown B, Birath K. Ranges of alpha-amylase activities in human serum and urine and correlations with some other alpha-amylase methods.  Clin Chim Acta. 1969;  26 445-453
  • 33 Polonsky K S, Rubenstein A H. C-peptide as a measure of the secretion and hepatic extraction of insulin.  Diabetes. 1984;  33 486-494
  • 34 Blix P M, Boddie-Willis C, Landau R L, Rochman H, Rubenstein A H. Urinary C-peptide: an indicator of beta-cell secretion under different metabolic conditions.  J Clin Endocrinol Metab. 1982;  54 574-580
  • 35 Krause U, von Erdmann B, Atzpodien W, Beyer J. C-peptide measurement: a simple method for the improvement of specificity.  J Immunoassay. 1981;  2 33-44
  • 36 Kumar M S, Schumacher O P, Deodar S D. Measurement of serum c-peptide immunoreactivity by radioimmunoassay in insulin-dependent diabetics.  Am J Clin Path. 1980;  74 78-82
  • 37 Gatling W, Row D JF, Hill R D. Microalbuminuria: an appraisal of assay techniques and urine collection procedures for measuring urinary albumin at low concentration. In: Mogensen CE (ed) The kidney and hypertension in diabetes mellitus. Boston; Martinus Nijhoff 1988: 41-50
  • 38 Ewing D J, Clarke B F. Diagnosis and management of diabetic autonomic neuropathy.  Brit Med J. 1982;  285 916-918
  • 39 Winer B J. Statistical principles in experimental design. New York; McGraw-Hill Book Company 1962
  • 40 Del Rosario M AF, Fitzgerald J F, Gupta S K, Croffie J M. Direct measurement of pancreatic enzymes after stimulation with secretin versus secretin plus cholecystokinin.  J Pediatr Gastroenterol Nutr. 2000;  31 28-32
  • 41 Pfefferkorn M D, Fitzgerald J F, Croffie J M, Gupta S K, Caffrey H M. Direct measurement of pancreatic enzymes: A comparison of secretogogues.  Dig Dis Sci. 2002;  47 2211-2216
  • 42 Sonwalkar S A, Holbrook I B, Phillips I, Kelly S M. A prospective, comparative study of the para-aminobenzoic acid test and faecal elastase 1 in the assessment of exocrine pancreatic function.  Aliment Pharmacol Ther. 2003;  17 467-471
  • 43 Luth S, Teyssen S, Forssmann K, Kolbel C, Krummenauer F, Singer M V. Fecal elastase-1 determination: ‘Gold standard’ of indirect pancreatic function tests?.  Scand J Gastroenterol. 2001;  10 1092-1099
  • 44 Icks A, Haastert B, Giani G, Rathmann W. Low fecal elastase-1 in type 1 diabetes mellitus.  Z Gastroenterol. 2001;  29 823-830
  • 45 Hardt P D, Krauss A, Bretz L, Porsch-Ozcurumez M, Schnell-Kretschmer H, Maser E, Bretzel R G, Zekorn T, Klor H U. Pancreatic exocrine function in patients with type 1 and type 2 diabetes mellitus.  Acta Diabetol. 2000;  37 105-110
  • 46 Chey W Y, Chang T M. Neural hormonal regulation of exocrine pancreatic secretion.  Pancreatology. 2001;  1 320-335
  • 47 Shimizu K, Shiratori K, Hayashi N, Fujiwara T, Horikoshi H. Effect of troglitazone on exocrine pancreas in rats with streptozotocin-induced diabetes mellitus.  Pancreas. 2000;  21 421-426
  • 48 Kawamori R, Katsura M, Ishida S, Yamasaki Y, Tujii M, Kawano S, Kamada T. Subclinical exocrine pancreatic derangement in human diabetic patients evaluated from pure pancreatic juice.  J Diabet Complic. 1995;  9 69-73

Arthur Swislocki, M. D.

Medicine Service (111E) · VA Northern California Health Care System ·

150 Muir Road · Martinez, CA 94553 · USA

Phone: +1 (925) 372-2076

Fax: +1 (925) 372-2185 ·

Email: Arthur.Swislocki@med.va.gov