Fig. 2.

The Insulin signalling pathway and Insulin resistance in COVID-19 and Diabetes infection.

Adapted from Jung & Choi (2014), Finucane and Davenport (2020), Rajpal et al. (2020) and Santos et al. (2021). Insulin binds to the insulin receptor (IR) to produce the activated insulin receptor substrate (IRS1). This leads activates phosphatidylinositol-3 kinase (PI3K), which binds to its receptor phosphatidylinositol-4,5-biphosphate (PIP₂) to form a second messenger, phosphatidylinositol-3, 4, 5-triphosphate (PIP₃). This activates Protein kinase B (AKT/PBK) which binds to the membrane, and is phosporylated by protein kinase-1(PDK1). Protein kinase B is essential for glucose transport activation, glycogenesis and lipogenesis. A dysregulation of the insulin signalling pathway due to viral infection disrupts the function of AKT/PKB and may lead to commodities such as hyperglycemia, dyslipidemia, Type 2 diabetes, obesity, chronic cardiovascular disease, and hypertension. The binding of the spike protein of SARS-CoV-2 in patients with commobidities and advanced age results in a hyperactive immune response and increases the severity of the virus after infection. Insulin resistance together with the hyperinflammation exacerbates the onset of all commodities and increase the pancreatic ACE2 expression. Increased pancreatic ACE2 expression creates a higher binding affinity for SARS-CoV-2. This predisposes patients with diabetes mellitus to suffer from a more aggressive pathology of COVID-19 infection.