Dear Colleagues,

Type I and type II diabetes mellitus, characterized by increased blood glucose levels, affect almost half a billion people around the world. Diabetes is caused due to either the inability to produce enough insulin or insufficiency of insulin action. Regardless of the types of diabetes, its complications involve microvascular, macrovascular, and neuropathic issues. Microvascular and macrovascular complications include nephropathy, retinopathy, neuropathy, cardiovascular disease, dyslipidemia, and hypertension. Diabetes mellitus accelerates mesenchymal activations in organs such as the kidneys and heart, influencing the pathways that regulate extracellular matrix (ECM) synthesis. The management of diabetes mellitus without any side effects is a challenge to the medical system. Very few specific therapeutics exist that minimize diabetic risk and mitigate its complications. In a preclinical settings, the regulation of oxidative stress, improving the quality of mitochondria, and targeting the pathways in diabetic complications have shown encouraging outcomes. Such interventions present a new approach for the management of diabetic complications, but further investigations are needed for better management.

Several molecules such as flavones, isoflavone, and chalcones have shown promising activity as inhibitors against drug targets, i.e., PTP1B, α-glucosidase, DPP-4, aldose reductase, SGLT-2 etc. in type 2 diabetes. These identified molecules have better efficacy in mouse models of diabetes mellitus when compared to standard drugs. In recent years, molecules targeting tissue-specific ANGPTL4, MST-1 inhibitors, and SGLT-2 inhibitors have been shown to be effective in combating diabetes mellitus. Moreover, catechol-o-methyl transferase (COMT) deficiency can lead to metabolic abnormalities such as diabetes mellitus, gestational diabetes and, pre-eclampsia in mice. Treatment with the COMT by-product 2-methoxy estradiol (2-ME) traversed the phenotype of metabolic syndrome in the mice; however, small- and large-scale random clinical trials are needed in patients before developing 2-ME as a medicine for human use.

The aim of this Special Issue is to cover new pathways and mechanisms in diabetes mellitus, investigating new approaches for the management of organ fibrosis in diabetes. In addition, we welcome articles that help to identify new management strategies of disease using new therapeutic approaches.

Potential topics include but are not limited to the following:

• New physiological mechanisms related to diabetic complications;
• Mesenchymal activation in diabetes;
• Organ fibrosis ;
• New targeted antidiabetic molecules;
• New approaches, such as siRNAs, microRNAs, long-noncoding RNAs, and therapeutic antisense oligonucleotides (ASOs);
• Small-scale trials and large RCTs to understand of the complex nature of diabetes and diabetic complications;
• New pharmacophores;
• Pharmacology of targeted molecules;
• The discovery of novel small synthetic molecules;
• Characterized plant-based synthetic molecules.

Dr. Swayam Prakash Srivastava
Guest Editor

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