Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Sep;47(3):193-9.
doi: 10.1007/s00592-009-0109-4. Epub 2009 Mar 31.

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

Jin-Kui Yang  1 , Shan-Shan Lin, Xiu-Juan Ji, Li-Min Guo
Affiliations

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

Jin-Kui Yang et al. Acta Diabetol. 2010 Sep.

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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
a Probability of event free (no death) survival among SARS patients divided into two groups [yes (red line) and no (green line)] for old age (≥60 years), male gender, anemia (Hb <10 for men and <9 for women), thrombocytopenia (<80 × 109 per l), low level of CD4 (<200) or CD8 (<150) lymphocytes, clinically significant elevation of ALT (≥80 IU/l), AST (≥80 IU/l), LDH (≥250 IU/l), s-Cr (≥106 μmol/l for men and ≥97 μmol/l for women), hypoxia (SaO2 <93%), and hyperglycemia (FPG ≥7.0 mmol/l). b Multivariate baseline predictors of death including old age (≥60 years), elevated ALT (≥80 IU/l), elevated LDH (≥250 IU/l) and hyperglycemia (FPG ≥7.0 mmol/l) among the SARS patients, presented by hazard ratio and 95% CI
Fig. 2
Fig. 2
Immunohistochemically specific pattern of staining for SARS-CoV receptor protein in different organs. Serial sections of the pancreas. a Hematoxylin-eosin (HE) stain shows the exocrine tissue of pancreas (red) with a pancreatic islet (in the middle). b Negative immunostaining control shows no non-specific staining especially caused by endogenous biotin. c Expression of ACE2 in pancreas as assessed by immunohistochemistry shows endocrine tissue is strongly positive compared with exocrine tissue. d Lung: marked ACE2 immunostaining was found in type I and type II alveolar epithelial cells, and capillary endothelium. e Kidney: ACE2 was very weakly present in glomerular visceral and parietal epithelium, but strongly present in the brush border and cytoplasm of proximal tubular cells, and in the cytoplasm of distal tubules and collecting ducts. f Heart: ACE2 was present in the myocytes, myocardium, border zone, endothelium of small-to-large arteries as well as sporadically within the smooth muscle of these vessels. g Liver: Küpffer cells, hepatocytes, and the endothelium of sinusoids were negative
Fig. 3
Fig. 3
Changes in FPG levels during the clinical course of SARS during follow-up. Non-SARS: FPG level in patients initially suspected of having SARS but later diagnosed with non-SARS pneumonia; SARS-0: the initial FPG level in SARS patients within 3 days after hospitalization; SARS-2: the initial FPG level after 2 weeks of hospitalization; SARS-D: the final FPG level before discharge; SARS-P: the FPG level from the follow-up study; Controls: the FPG level in the healthy siblings of SARS patients. **P < 0.01 versus non-SARS patients. †† P < 0.01 versus controls
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. 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. Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet Med. 2006;23:623–628. doi: 10.1111/j.1464-5491.2006.01861.x. - DOI - PubMed
    1. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circ Res. 2000;87:E1–E9. - PubMed
    1. Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000;275:33238–33243. doi: 10.1074/jbc.M002615200. - DOI - PubMed
    1. Turner AJ, Hiscox JA, Hooper NM. ACE2: from vasopeptidase to SARS virus receptor. Trends Pharmacol Sci. 2004;25:291–294. doi: 10.1016/j.tips.2004.04.001. - DOI - PMC - PubMed
    1. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426:450–454. doi: 10.1038/nature02145. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances