Skip to main content
Erschienen in: Acta Diabetologica 3/2010

01.09.2010 | Original Article

Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes

verfasst von: Jin-Kui Yang, Shan-Shan Lin, Xiu-Juan Ji, Li-Min Guo

Erschienen in: Acta Diabetologica | Ausgabe 3/2010

Einloggen, um Zugang zu erhalten

Abstract

Multiple organ damage in severe acute respiratory syndrome (SARS) patients is common; however, the pathogenesis remains controversial. This study was to determine whether the damage was correlated with expression of the SARS coronavirus receptor, angiotensin converting enzyme 2 (ACE2), in different organs, especially in the endocrine tissues of the pancreas, and to elucidate the pathogenesis of glucose intolerance in SARS patients. The effect of clinical variables on survival was estimated in 135 SARS patients who died, 385 hospitalized SARS patients who survived, and 19 patients with non-SARS pneumonia. A total of 39 SARS patients who had no previous diabetes and received no steroid treatment were compared to 39 matched healthy siblings during a 3-year follow-up period. The pattern of SARS coronavirus receptor-ACE2 proteins in different human organs was also studied. Significant elevations in oxygen saturation, serum creatinine, lactate dehydrogenase, creatine kinase MB isoenzyme, and fasting plasma glucose (FPG), but not in alanine transaminase were predictors for death. Abundant ACE2 immunostaining was found in lung, kidney, heart, and islets of pancreas, but not in hepatocytes. Twenty of the 39 followed-up patients were diabetic during hospitalization. After 3 years, only two of these patients had diabetes. Compared with their non-SARS siblings, these patients exhibited no significant differences in FPG, postprandial glucose (PPG), and insulin levels. The organ involvements of SARS correlated with organ expression of ACE2. The localization of ACE2 expression in the endocrine part of the pancreas suggests that SARS coronavirus enters islets using ACE2 as its receptor and damages islets causing acute diabetes.
Literatur
1.
Zurück zum Zitat Yang JK, Feng Y, Yuan MY, Yuan SY, Fu HJ, Wu BY, Sun GZ, Yang GR, Zhang XL, Wang L, Xu X, Xu XP, Chan JC (2006) Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet Med 23:623–628CrossRefPubMed Yang JK, Feng Y, Yuan MY, Yuan SY, Fu HJ, Wu BY, Sun GZ, Yang GR, Zhang XL, Wang L, Xu X, Xu XP, Chan JC (2006) Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet Med 23:623–628CrossRefPubMed
2.
Zurück zum Zitat Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S (2000) A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circ Res 87:E1–E9PubMed Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S (2000) A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circ Res 87:E1–E9PubMed
3.
Zurück zum Zitat Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ (2000) A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem 275:33238–33243CrossRefPubMed Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ (2000) A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem 275:33238–33243CrossRefPubMed
4.
Zurück zum Zitat Turner AJ, Hiscox JA, Hooper NM (2004) ACE2: from vasopeptidase to SARS virus receptor. Trends Pharmacol Sci 25:291–294CrossRefPubMed Turner AJ, Hiscox JA, Hooper NM (2004) ACE2: from vasopeptidase to SARS virus receptor. Trends Pharmacol Sci 25:291–294CrossRefPubMed
5.
Zurück zum Zitat Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M (2003) Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426:450–454CrossRefPubMed Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M (2003) Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426:450–454CrossRefPubMed
6.
Zurück zum Zitat Booth CM, Matukas LM, Tomlinson GA, Rachlis AR, Rose DB, Dwosh HA, Walmsley SL, Mazzulli T, Avendano M, Derkach P, Ephtimios IE, Kitai I, Mederski BD, Shadowitz SB, Gold WL, Hawryluck LA, Rea E, Chenkin JS, Cescon DW, Poutanen SM, Detsky AS (2003) Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA 289:2801–2809CrossRefPubMed Booth CM, Matukas LM, Tomlinson GA, Rachlis AR, Rose DB, Dwosh HA, Walmsley SL, Mazzulli T, Avendano M, Derkach P, Ephtimios IE, Kitai I, Mederski BD, Shadowitz SB, Gold WL, Hawryluck LA, Rea E, Chenkin JS, Cescon DW, Poutanen SM, Detsky AS (2003) Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA 289:2801–2809CrossRefPubMed
7.
Zurück zum Zitat Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419CrossRefPubMed Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419CrossRefPubMed
8.
9.
Zurück zum Zitat Hamming I, Timens W, Bulthuis ML, Lely AT, Navis GJ, van Goor H (2004) Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 203:631–637CrossRefPubMed Hamming I, Timens W, Bulthuis ML, Lely AT, Navis GJ, van Goor H (2004) Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 203:631–637CrossRefPubMed
10.
Zurück zum Zitat Harmer D, Gilbert M, Borman R, Clark KL (2002) Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett 532:107–110CrossRefPubMed Harmer D, Gilbert M, Borman R, Clark KL (2002) Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett 532:107–110CrossRefPubMed
11.
Zurück zum Zitat Lang ZW, Zhang LJ, Zhang SJ, Meng X, Li JQ, Song CZ, Sun L, Zhou YS, Dwyer DE (2003) A clinicopathological study of three cases of severe acute respiratory syndrome (SARS). Pathology 35:526–531CrossRefPubMed Lang ZW, Zhang LJ, Zhang SJ, Meng X, Li JQ, Song CZ, Sun L, Zhou YS, Dwyer DE (2003) A clinicopathological study of three cases of severe acute respiratory syndrome (SARS). Pathology 35:526–531CrossRefPubMed
12.
Zurück zum Zitat Lang Z, Zhang L, Zhang S, Meng X, Li J, Song C, Sun L, Zhou Y (2003) Pathological study on severe acute respiratory syndrome. Chin Med J (Engl) 116:976–980 Lang Z, Zhang L, Zhang S, Meng X, Li J, Song C, Sun L, Zhou Y (2003) Pathological study on severe acute respiratory syndrome. Chin Med J (Engl) 116:976–980
13.
Zurück zum Zitat Ding Y, Wang H, Shen H, Li Z, Geng J, Han H, Cai J, Li X, Kang W, Weng D, Lu Y, Wu D, He L, Yao K (2003) The clinical pathology of severe acute respiratory syndrome (SARS): a report from China. J Pathol 200:282–289CrossRefPubMed Ding Y, Wang H, Shen H, Li Z, Geng J, Han H, Cai J, Li X, Kang W, Weng D, Lu Y, Wu D, He L, Yao K (2003) The clinical pathology of severe acute respiratory syndrome (SARS): a report from China. J Pathol 200:282–289CrossRefPubMed
14.
Zurück zum Zitat Shi X, Gong E, Gao D, Zhang B, Zheng J, Gao Z, Zhong Y, Zou W, Wu B, Fang W, Liao S, Wang S, Xie Z, Lu M, Hou L, Zhong H, Shao H, Li N, Liu C, Pei F, Yang J, Wang Y, Han Z, Shi X, Zhang Q, You J, Zhu X, Gu J (2005) Severe acute respiratory syndrome associated coronavirus is detected in intestinal tissues of fatal cases. Am J Gastroenterol 100:169–176CrossRefPubMed Shi X, Gong E, Gao D, Zhang B, Zheng J, Gao Z, Zhong Y, Zou W, Wu B, Fang W, Liao S, Wang S, Xie Z, Lu M, Hou L, Zhong H, Shao H, Li N, Liu C, Pei F, Yang J, Wang Y, Han Z, Shi X, Zhang Q, You J, Zhu X, Gu J (2005) Severe acute respiratory syndrome associated coronavirus is detected in intestinal tissues of fatal cases. Am J Gastroenterol 100:169–176CrossRefPubMed
15.
Zurück zum Zitat Ding Y, He L, Zhang Q, Huang Z, Che X, Hou J, Wang H, Shen H, Qiu L, Li Z, Geng J, Cai J, Han H, Li X, Kang W, Weng D, Liang P, Jiang S (2004) Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J Pathol 203:622–630CrossRefPubMed Ding Y, He L, Zhang Q, Huang Z, Che X, Hou J, Wang H, Shen H, Qiu L, Li Z, Geng J, Cai J, Han H, Li X, Kang W, Weng D, Liang P, Jiang S (2004) Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J Pathol 203:622–630CrossRefPubMed
16.
Zurück zum Zitat Paizis G, Tikellis C, Cooper ME, Schembri JM, Lew RA, Smith AI, Shaw T, Warner FJ, Zuilli A, Burrell LM, Angus PW (2005) Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2. Gut 54:1790–1796CrossRefPubMed Paizis G, Tikellis C, Cooper ME, Schembri JM, Lew RA, Smith AI, Shaw T, Warner FJ, Zuilli A, Burrell LM, Angus PW (2005) Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2. Gut 54:1790–1796CrossRefPubMed
17.
18.
Zurück zum Zitat Roivainen M, Rasilainen S, Ylipaasto P, Nissinen R, Ustinov J, Bouwens L, Eizirik DL, Hovi T, Otonkoski T (2000) Mechanisms of coxsackievirus-induced damage to human pancreatic beta-cells. J Clin Endocrinol Metab 85:432–440CrossRefPubMed Roivainen M, Rasilainen S, Ylipaasto P, Nissinen R, Ustinov J, Bouwens L, Eizirik DL, Hovi T, Otonkoski T (2000) Mechanisms of coxsackievirus-induced damage to human pancreatic beta-cells. J Clin Endocrinol Metab 85:432–440CrossRefPubMed
19.
Zurück zum Zitat Jali MV, Shankar PS (1990) Transient diabetes following chicken pox. J Assoc Physicians India 38:663–664PubMed Jali MV, Shankar PS (1990) Transient diabetes following chicken pox. J Assoc Physicians India 38:663–664PubMed
Metadaten
Titel
Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes
verfasst von
Jin-Kui Yang
Shan-Shan Lin
Xiu-Juan Ji
Li-Min Guo
Publikationsdatum
01.09.2010
Verlag
Springer Milan
Erschienen in
Acta Diabetologica / Ausgabe 3/2010
Print ISSN: 0940-5429
Elektronische ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-009-0109-4

Weitere Artikel der Ausgabe 3/2010

Acta Diabetologica 3/2010 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.