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1.
Mol Biol Rep ; 49(3): 2321-2324, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1664478

ABSTRACT

Numerous studies demonstrate parallels between CVD, type 2 diabetes mellitus (T2DM) and COVID-19 pathology, which accentuate pre-existing complications in patients infected with COVID-19 and potentially exacerbate the infection course. Antidiabetic drugs such as sodium-glucose transporter-2 (SGLT-2) inhibitors have garnered substantial attention recently due to their efficacy in reducing the severity of cardiorenal disease. The effect of SGLT-2 inhibitors in patients with COVID-19 remains unclear particularly since SGLT-2 inhibitors contribute to altering the RAAS cascade activity, which includes ACE-2, the major cell entry receptor for SARS-CoV2. A study, DARE-19, was carried out to unveil the effects of SGLT-2 inhibitor treatment on comorbid disease complications and concomitant COVID-19 outcomes and demonstrated no statistical significance. However, the need for further studies is essential to provide conclusive clinical findings.


Subject(s)
Benzhydryl Compounds/therapeutic use , COVID-19/complications , Glucosides/therapeutic use , Renin-Angiotensin System/drug effects , Respiratory Insufficiency/drug therapy , SARS-CoV-2 , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Angiotensin-Converting Enzyme 2/physiology , Clinical Trials, Phase III as Topic , Double-Blind Method , Drug Repositioning , Heart Diseases/prevention & control , Humans , Kidney Diseases/prevention & control , Mitochondria/drug effects , Multicenter Studies as Topic , Oxidative Stress/drug effects , Randomized Controlled Trials as Topic , Receptors, Virus/physiology , Respiratory Insufficiency/etiology , Sodium-Glucose Transporter 2/physiology , Sodium-Glucose Transporter 2 Inhibitors/pharmacology
2.
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.


Subject(s)
COVID-19/complications , COVID-19/pathology , Diabetes Mellitus , Obesity/complications , SARS-CoV-2 , Adipose Tissue/metabolism , Adrenergic beta-3 Receptor Agonists/pharmacology , Aged , Aging , Angiotensin-Converting Enzyme 2/metabolism , Animals , Cell Line , Humans , Hyperinsulinism/complications , Hyperinsulinism/drug therapy , Hypoglycemic Agents/pharmacology , Metformin/therapeutic use , Mice , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Spike Glycoprotein, Coronavirus/metabolism , Up-Regulation , Virus Internalization
3.
Diabetes ; 70(12): 2745-2755, 2021 12.
Article in English | MEDLINE | ID: covidwho-1456233

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.


Subject(s)
COVID-19/complications , COVID-19/pathology , Diabetes Mellitus , Obesity/complications , SARS-CoV-2 , Adipose Tissue/metabolism , Adrenergic beta-3 Receptor Agonists/pharmacology , Aged , Aging , Angiotensin-Converting Enzyme 2/metabolism , Animals , Cell Line , Humans , Hyperinsulinism/complications , Hyperinsulinism/drug therapy , Hypoglycemic Agents/pharmacology , Metformin/therapeutic use , Mice , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Spike Glycoprotein, Coronavirus/metabolism , Up-Regulation , Virus Internalization
4.
Diabetes Metab Syndr ; 15(1): 159-167, 2021.
Article in English | MEDLINE | ID: covidwho-987529

ABSTRACT

BACKGROUND & AIMS: Several observational studies have recently reported the outcomes of non-insulin anti-diabetic agents (ADA) in patients with T2DM and coronavirus disease 2019 (COVID-19). We sought to review the literature to appraise the clinicians on these outcomes. METHODS: A literature search using the specific keywords was carried out in the database of PubMed, MedRxiv and Google Scholar up till December 11, 2020 applying Boolean method. Full text of all the relevant articles that reported the outcomes of ADA in patients with T2DM and COVID-19 were retrieved. Subsequently, an appraisal of literature report was narratively presented. RESULTS: Available studies that reported the outcomes of ADA are either case series or retrospective cohorts or prospective observational studies, in absence of the randomized controlled trials (RCTs). Results from these observational studies suggest that amongst all the non-insulin ADA, metformin users prior to the hospitalization had improved outcomes compared to the non-users. Data for dipeptidyl-peptidase-4 inhibitors (DPP-4i) are encouraging although inconsistent. No documentation of any harm or benefit has been observed for sulfonylureas (SUs), sodium glucose co-transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide receptor agonists (GLP-1RAs). No data is yet available for pioglitazone. CONCLUSION: Metformin and DPP-4i should be continued in patients with T2DM until hospitalization or unless contraindicated. No evidence of harm suggests that SUs, SGLT-2i or GLP-1RAs may not be stopped unless very sick, hospitalized or contraindicated. The results from RCTs are needed to claim any meaningful benefit with either metformin or DPP-4i in patients with T2DM and COVID-19.


Subject(s)
COVID-19/drug therapy , COVID-19/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Hypoglycemic Agents/therapeutic use , Blood Glucose/drug effects , Blood Glucose/metabolism , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Humans , Hypoglycemic Agents/pharmacology , Metformin/pharmacology , Metformin/therapeutic use , Prospective Studies , Retrospective Studies , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
5.
Exp Clin Endocrinol Diabetes ; 130(3): 198-199, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-759628

ABSTRACT

Novel coronavirus infectious disease (COVID-19) has been recognised as a pandemic by the World Health Organization (WHO) 1. Mortality and morbidity are higher in elderly individuals and those with comorbidities, such as diabetes mellitus (DM), obesity, hypertension, respiratory tract diseases, coronary heart disease or cancer 1. Indeed, two thirds of individuals who died from COVID-19 had DM in Italy 2.


Subject(s)
COVID-19 , Communicable Diseases , Diabetes Mellitus, Type 2 , Sodium-Glucose Transporter 2 Inhibitors , Aged , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Glucose , Humans , Sodium , Sodium-Glucose Transporter 2 Inhibitors/pharmacology
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