FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 330:313-318 February 3, 1994 Number 5 Next

	Full Text Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background The diabetes mellitus that occurs in patients with pancreatic cancer is characterized by marked insulin resistance that declines after tumor resection. Islet amyloid polypeptide (IAPP), a hormonal factor secreted from the pancreatic beta cells, reduces insulin sensitivity in vivo and glycogen synthesis in vitro. In this study, we examined the relation between IAPP and diabetes in patients with pancreatic cancer.

Methods We measured IAPP in plasma from 30 patients with pancreatic cancer, 46 patients with other cancers, 23 patients with diabetes, and 25 normal subjects. IAPP immunoreactivity and IAPP messenger RNA were studied in pancreatic cancers, pancreatic tissue adjacent to cancers, and normal pancreatic tissue.

Results Plasma IAPP concentrations were elevated in the patients with pancreatic cancer as compared with the normal subjects (mean [±SD], 22.3 ±13.6 vs. 8.0 ±5.0 pmol per liter; P<0.001), normal in the patients with other cancers, and normal or low in the patients with diabetes. Among the patients with pancreatic cancer, the concentrations were 25.0 ±8.7 pmol per liter in the 7 patients with diabetes who required insulin, 31.4 ±12.6 pmol per liter in the 11 patients with diabetes who did not require insulin, and 12.2 ±2.4 pmol per liter in the 9 patients with normal glucose tolerance (3 patients had impaired glucose tolerance; their mean plasma IAPP concentration was 11.7 ±5.5 pmol per liter). Plasma IAPP concentrations decreased after surgery in the seven patients with pancreatic cancer who were studied before and after subtotal pancreatectomy (28.9 ±16.4 vs. 5.6 ±3.4 pmol per liter, P = 0.01). Pancreatic cancers contained IAPP, but the concentrations were lower than in normal pancreatic tissue (17 ±16 vs. 183 ±129 pmol per gram, P<0.001). In samples from the patients with both pancreatic cancer and diabetes, immunostaining for IAPP was reduced in islets of pancreatic tissue surrounding the tumor; in situ hybridization studies suggested that transcription occurred normally in these islets.

Conclusions Plasma IAPP concentrations are elevated in patients with pancreatic cancer who have diabetes. Since IAPP may cause insulin resistance, its overproduction may contribute to the diabetes that occurs in these patients.

Source Information

From the Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebr. (J.P., M.K.H., T.E.A.); the Departments of Surgery (J.P., J.L.) and Pathology (G.T.W., P.W.), University of Linkoping, Linkoping, Sweden; the Department of Pathology, University of Uppsala, Uppsala, Sweden (L.C.); and the Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha (P.M.P.).

Address reprint requests to Dr. Adrian at the Department of Biomedical Sciences, Creighton University School of Medicine, 2500 California St., Omaha, NE 68178.

Full Text of this Article

This article has been cited by other articles:

• Stolzenberg-Solomon, R. Z., Adams, K., Leitzmann, M., Schairer, C., Michaud, D. S., Hollenbeck, A., Schatzkin, A., Silverman, D. T. (2008). Adiposity, Physical Activity, and Pancreatic Cancer in the National Institutes of Health-AARP Diet and Health Cohort. Am J Epidemiol 167: 586-597 [Abstract] [Full Text]  
• Wang, F., Gupta, S., Holly, E. A. (2006). Diabetes mellitus and pancreatic cancer in a population-based case-control study in the san francisco bay area, california.. Cancer Epidemiol. Biomarkers Prev. 15: 1458-1463 [Abstract] [Full Text]  
• Hennig, R., Ding, X.-Z., Tong, W.-G., Schneider, M. B., Standop, J., Friess, H., Buchler, M. W., Pour, P. M., Adrian, T. E. (2002). 5-Lipoxygenase and Leukotriene B4 Receptor Are Expressed in Human Pancreatic Cancers But Not in Pancreatic Ducts in Normal Tissue. Am. J. Pathol. 161: 421-428 [Abstract] [Full Text]  
• Tateishi, K., DiMagno, E. P., Klee, G. G. (2001). Plasma Islet Amyloid Polypeptide Is Not an Effective Tumor Marker for Pancreatic Cancer Even When Protease Inhibitors and Rapid Freezing of Specimens Are Utilized. Clin. Chem. 47: 2071-2073 [Full Text]  
• Sakagashira, S., Hiddinga, H. J., Tateishi, K., Sanke, T., Hanabusa, T., Nanjo, K., Eberhardt, N. L. (2000). S20G Mutant Amylin Exhibits Increased in Vitro Amyloidogenicity and Increased Intracellular Cytotoxicity Compared to Wild-Type Amylin. Am. J. Pathol. 157: 2101-2109 [Abstract] [Full Text]  
• Hart, A. R (1999). Classic diseases revisited: Pancreatic cancer: any prospects for prevention?. Postgrad. Med. J. 75: 521-526 [Abstract] [Full Text]  
• Tingstedt, J.-E., Edlund, H., Madsen, O. D., Larsson, L.-I. (1999). Gastric Amylin Expression: Cellular Identity and Lack of Requirement for the Homeobox Protein PDX-1. A Study in Normal and PDX-1-Deficient Animals with a Cautionary Note on Antiserum Evaluation. J. Histochem. Cytochem. 47: 973-980 [Abstract] [Full Text]  
• Arnelo, U., Reidelberger, R., Adrian, T. E., Larsson, J., Permert, J. (1998). Sufficiency of postprandial plasma levels of islet amyloid polypeptide for suppression of feeding in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 275: R1537-R1542 [Abstract] [Full Text]  
• Arnelo, U., Permert, J., Larsson, J., Reidelberger, R. D., Arnelo, C., Adrian, T. E. (1997). Chronic Low Dose Islet Amyloid Polypeptide Infusion Reduces Food Intake, But Does Not Influence Glucose Metabolism, in Unrestrained Conscious Rats: Studies Using a Novel Aortic Catheterization Technique. Endocrinology 138: 4081-4085 [Abstract] [Full Text]  
• Gullo, L., Pezzilli, R., Morselli-Labate, A. M., Italian Pancreatic Cancer Study Group, (1994). Diabetes and the Risk of Pancreatic Cancer. NEJM 331: 81-84 [Abstract] [Full Text]