Lipotoxicity-polarised macrophage-derived exosomes regulate mitochondrial fitness through Miro1-mediated mitophagy inhibition and contribute to type 2 diabetes development in mice

Investigating Novel Thiophene Carbaldehyde Based Thiazole Derivatives as Potential Hits for Diabetic Management: Synthesis, In Vitro and In Silico Approach

“…[38,39] The α-1-4 bond linkage in starch or oligosaccharides is broken down by this enzyme into monosaccharides like glucose. [40,41] Therefore, α-glucosidase suppression can aid in preventing post-prandial hyperglycemia and its related consequences. [42][43][44] The synthesis of Schiff base compounds bearing thiazole nucleus of thiophene carbaldehyde showed a deliberate approach in the search for novel antidiabetic agents.…”

“…Controlling the catalytic activity of the enzyme α‐glucosidase (EC.3.2.1.20), located in the small intestine, is one strategy for treating this condition [38,39] . The α‐1‐4 bond linkage in starch or oligosaccharides is broken down by this enzyme into monosaccharides like glucose [40,41] . Therefore, α‐glucosidase suppression can aid in preventing post‐prandial hyperglycemia and its related consequences [42–44] .…”

Synthesis of Flurbiprofen Based Amide Derivatives as Potential Leads for Diabetic Management: In Vitro α‐glucosidase Inhibition, Molecular Docking and DFT Simulation Approach

“…Hyperglycemia arising from inadequate insulin action and a decreased secretion of insulin, or both illustrates this particular category of metabolic conditions [3] . The malfunctioning, lasting damage, and insufficiency of numerous organs, including the eyes, heart, kidneys, blood vessels, and nerves, are all connected with to chronic hyperglycemia [4,5] . It is actually categorized as type‐I and type‐II DM.…”

Epigenetic modifications in obesity‐associated diseases

“…In obese patients with T2D, there is an elevation in hsa‐miR‐551b‐3p levels in both VAT and serum exosomes compared with obese patients without T2D, suggesting a potential association between miRNAs secretion and obesity‐induced lipid remodeling 172 . Furthermore, miR‐27‐3p overexpression in exosomes originating from M1 macrophages results in impaired mitochondrial autophagy through the suppression of ras homolog family member T1 (Rhot1) gene, which encodes mitochondrial rho GTPase 1 173 . Mitochondria dynamics are believed to contribute to the advancement of diabetes, as autophagic impairments within the mitochondria can exacerbate oxidative stress in β cells and foster IR 174 .…”

“…HFD could lead to M1 polarization of bone marrow macrophages (BMMs), and the elevated miR‐143‐5P derived from BMMs could induce IR in hepatocytes 224 . In addition, high expression of miR‐27‐3p in M1 macrophages induced by a HFD leads to the disruption of mitochondrial autophagy, which exacerbates IR 173 . Berberine is known to alleviate obesity, IR and liver injury by inhibiting macrophages from releasing miR‐155‐5p, which protects the liver from lipotoxicity 225 .…”