The maintenance of iron homeostasis is essential for proper endocrine function. A growing body of evidence suggests that iron imbalance is a key factor in the development of several endocrine diseases. Nowadays, ferroptosis, an iron-dependent form of regulated cell death, has become increasingly recognized as an important process to mediate the pathogenesis and progression of type 2 diabetes mellitus (T2DM). It has been shown that ferroptosis in pancreas β cells leads to decreased insulin secretion; and ferroptosis in the liver, fat, and muscle induces insulin resistance. Understanding the mechanisms concerning the regulation of iron metabolism and ferroptosis in T2DM may lead to improved disease management. In this review, we summarized the connection between the metabolic pathways and molecular mechanisms of iron metabolism and ferroptosis in T2DM. Additionally, we discuss the potential targets and pathways concerning ferroptosis in treating T2DM and analysis the current limitations and future directions concerning these novel T2DM treatment targets.

The pancreatic duodenum homeobox-1 (PDX-1) is a transcription factor encoded by a Hox-like homeodomain gene that plays a crucial role in pancreatic development, β-cell differentiation, and the maintenance of mature β-cell functions. Research on the relationship between PDX-1 and diabetes has gained much attention because of the increasing prevalence of diabetes melitus (DM). Recent studies have shown that the overexpression of PDX-1 regulates pancreatic development and promotes β-cell differentiation and insulin secretion. It also plays a vital role in cell remodeling, gene editing, and drug development. Conversely, the absence of PDX-1 increases susceptibility to DM. Therefore, in this review, we summarized the role of PDX-1 in pancreatic development and the pathogenesis of DM. A better understanding of PDX-1 will deepen our knowledge of the pathophysiology of DM and provide a scientific basis for exploring PDX-1 as a potential target for treating diabetes.

Traditional Chinese medicine (TCM) has long been used to treat diabetes mellitus and angina. It has also gained widespread clinical applications in China as a common adjuvant treatment. Although there is high-quality evidence that TCM is effective in regulating glucose and lipid metabolism, the cardiovascular protective effect of TCM in the treatment of diabetes mellitus has not been fully elucidated, especially in patients with both diabetes mellitus and coronary heart disease (CHD). We systematically assessed the efficacy and safety of TCM for the adjuvant treatment of patients with CHD and diabetes mellitus and examined the pharmacological effects and potential mechanisms of TCM medication/herbs on diabetes mellitus with CHD. We found that TCM could improve the control effect of conventional treatment on cardiac function, hemorheology, blood glucose, blood lipid, and inflammation, thus reducing the frequency of angina and the incidence of cardiovascular events and all-cause mortality. These findings indicate that TCM may be used as a complementary approach for patients with diabetes mellitus and CHD. Nevertheless, more rigorously designed randomized controlled trials and long-term evaluations are needed to support these findings.

Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is rising, increasing risks of cirrhosis and hepatocellular carcinoma. The herbal formula Jiangtang Tiaozhi (JTTZF) clinically alleviates MASLD and hepatic steatosis. This study aimed to investigate the therapeutic effects and underlying mechanisms of JTTZF in treating MASLD via the crosstalk between peroxisomes and lipid droplets in hepatocytes. C57BL/6 J mice on a high-fat diet (HFD) modeling MASLD received daily JTTZF or water for 12 weeks. Serum biomarkers, histology, and liver multi-omics analyses assessed metabolic status, steatosis, targets, and pathways. Oleic acid/palmitic acid-induced HepG2 cells treated with JTTZF-containing serum or ABCD2 overexpression. Mass spectrometry identified JTTZF bioavailable components. Molecular techniques evaluated effects on β-oxidation enzymes, lipid droplet proteins, peroxisomal proteins, and oxidative stress. JTTZF significantly improved glucose and lipid metabolism and hepatic steatosis in HFD-fed mice and reduced lipid droplets in liver and in HepG2 cells. DHE staining and ROS flow cytometry confirmed that JTTZF alleviated ROS levels. Multi-omics and validation using RT-PCR, western blotting, and immunohistochemistry revealed that JTTZF regulated enzymes for very long-chain fatty acid metabolism and fatty acid metabolism reprogramming in hepatocellular. Gene overexpression validated JTTZF downregulated the peroxisomal ABCD2 transporter. Mechanistically, JTTZF enhanced lipid droplet metabolism and reduced ROS via the ABCD2/PEX2/ATGL axis, ameliorating insulin resistance and MASLD. This study establishes a hepatocellular fatty acid metabolic reprogramming network in MASLD. Targeting the ABCD2/PEX2/ATGL axis represents a promising therapeutic strategy, with JTTZF showing potential as a therapeutic agent for MASLD.