New-onset diabetes in COVID-19: The molecular pathogenesis.

Diabetes mellitus (DM) is still a challenging metabolic disease worldwide. In the current situation, the world is facing a COVID-19 pandemic due to SARS-CoV-2 infection. DM is one of the comorbid conditions that can worsen the severity of the COVID-19 condition. Surprisingly, SARS-CoV-2 infection can induce new-onset diabetes, a condition in which acute hyperglycemia occurs and may develop into a complication in nondiabetic patients. Angiotensinconverting enzyme 2 (ACE2) is a crucial entry factor for SARS-CoV-2 infection. ACE2 will bind to the spike protein of SARS-CoV-2, potentially initiating a damaging process in many tissues in the human body, including metabolic tissues. This mechanism suggests a potential role of ACE2 in the pathogenesis of diabetes since ACE2 has been proven to localize in essential metabolic tissues, one of which is the acini and islets part of the pancreas. This interrelated ACE2 in COVID-19 and DM is thought of as the mechanism that induces new-onset diabetes in COVID-19 patients. This review will thoroughly describe the current findings and theories regarding the molecular mechanism of SARS-CoV-2-induced new-onset diabetes and the possible therapeutic intervention.

Chaperone-Based Therapeutic Target Innovation: Heat Shock Protein 70 (HSP70) for Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is still a global health problem. Current T2DM treatments are limited to curing the symptoms and have not been able to restore insulin sensitivity in insulin-sensitive tissues that have become resistant. In the past decade, some studies have shown the significant role of a chaperone family, heat shock protein 70 (HSP70), in insulin resistance pathogenesis that leads to T2DM. HSP70 is a cytoprotective molecular chaperone that functions in protein folding and degradation. In general, studies have shown that decreased concentration of HSP70 is able to induce inflammation process through JNK activation, inhibit fatty acid oxidation by mitochondria through mitophagy decrease and mitochondrial biogenesis, as well as activate SREBP-1c, one of the lipogenic gene transcription factors in ER stress. The overall molecular pathways are potentially leading to insulin resistance and T2DM. Increased expression of HSP70 in brain tissues is able to improve insulin sensitivity and glycemic control specifically. HSP70 modulation-targeting strategies (including long-term physical exercise, hot tub therapy (HTT), and administration of alfalfa-derived HSP70 (aHSP70)) in subjects with insulin resistance are proven to have therapeutic and preventive potency that are promising in T2DM management.