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Possible Involvement of Adipose Tissue in Patients With Older Age, Obesity, and Diabetes With SARS-CoV-2 Infection (COVID-19) via GRP78 (BIP/HSPA5): Significance of Hyperinsulinemia Management in COVID-19.
Shin, Jihoon; Toyoda, Shinichiro; Nishitani, Shigeki; Fukuhara, Atsunori; Kita, Shunbun; Otsuki, Michio; Shimomura, Iichiro.
  • Shin J; Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan shinjihoon0209@gmail.com shinjihoon0209@endmet.med.osaka-u.ac.jp.
  • Toyoda S; Department of Diabetes Care Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Nishitani S; Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Fukuhara A; Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Kita S; Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Otsuki M; Department of Adipose Management, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Shimomura I; Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Diabetes ; 70(12): 2745-2755, 2021 12.
Article in English | MEDLINE | ID: covidwho-1556100
ABSTRACT
Aging, obesity, and diabetes are major risk factors for the severe progression and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019 [COVID-19]), but the underlying mechanism is not yet fully understood. In this study, we found that the SARS-CoV-2 spike protein physically interacts with cell surface GRP78, which promotes the binding to and accumulation in ACE2-expressing cells. GRP78 was highly expressed in adipose tissue and increased in humans and mice with older age, obesity, and diabetes. The overexpression of GRP78 was attributed to hyperinsulinemia in adipocytes, which was in part mediated by the stress-responsive transcription factor XBP-1s. Management of hyperinsulinemia by pharmacological approaches, including metformin, sodium-glucose cotransporter 2 inhibitor, or ß3-adrenergic receptor agonist, decreased GRP78 gene expression in adipose tissue. Environmental interventions, including exercise, calorie restriction, fasting, or cold exposure, reduced the gene expression of GRP78 in adipose tissue. This study provides scientific evidence for the role of GRP78 as a binding partner of the SARS-CoV-2 spike protein and ACE2, which might be related to the severe progression and outcome of COVID-19 in patients with older age, obesity, and diabetes. The management of hyperinsulinemia and the related GRP78 expression could be a therapeutic or preventative target.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Diabetes Mellitus / SARS-CoV-2 / COVID-19 / Endoplasmic Reticulum Chaperone BiP / Obesity Type of study: Prognostic study Topics: Long Covid Limits: Aged / Animals / Humans Language: English Journal: Diabetes Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Diabetes Mellitus / SARS-CoV-2 / COVID-19 / Endoplasmic Reticulum Chaperone BiP / Obesity Type of study: Prognostic study Topics: Long Covid Limits: Aged / Animals / Humans Language: English Journal: Diabetes Year: 2021 Document Type: Article