humanin and Diabetes-Mellitus

Humanin (HN) is a small mitochondrial-derived cytoprotective polypeptide encoded by mtDNA. HN exhibits protective effects in several cell types, including leukocytes, germ cells, neurons, tissues against cellular stress conditions and apoptosis through regulating various signaling mechanisms, such as JAK/STAT pathway and interaction of BCL-2 family of protein. HN is an essential cytoprotective peptide in the human body that regulates mitochondrial functions under stress conditions. The present review aims to evaluate HN peptide's antiapoptotic activities as a potential therapeutic target in the treatment of cancer, diabetes mellitus, male infertility, bone-related diseases, cardiac diseases, and brain diseases. Based on in vitro and in vivo studies, HN significantly suppressed the apoptosis during the treatment of bone osteoporosis, cardiovascular diseases, diabetes mellitus, and neurodegenerative diseases. According to accumulated data, it is concluded that HN exerts the proapoptotic activity of TNF-α in cancer, which makes HN as a novel therapeutic agent in the treatment of cancer and suggested that along with HN, the development of another mitochondrial-derived peptide could be a viable therapeutic option against different oxidative stress and apoptosis-related diseases.

Topics: Amino Acid Sequence; Animals; Apoptosis; Apoptosis Regulatory Proteins; Cytoprotection; Diabetes Mellitus; Humans; Intracellular Signaling Peptides and Proteins; Mitochondria; Neoplasms; Neurodegenerative Diseases

Diabetes is known to cause cognitive impairments through various mechanisms, including oxidative stress, inflammation, and apoptosis. Humanin (HN) has been shown to have protective effects on cognitive impairments induced by factors such as Aβ, muscarinic receptor antagonists, and aging in rodents. However, the mechanisms underlying the protective effects of HN in the prefrontal cortex and hippocampus in the context of diabetes are not well understood. In this study, we aimed to investigate the potential protective role of HN on oxidative stress, inflammation, and apoptosis in mice with diabetes. We divided the mice into four groups, including a control group (treated with saline), a humanin group (treated with 4 mg/kg of HN), a streptozotocin (STZ) group (diabetic control), and an STZ+Humanin group. The mice were administered HN daily for 15 days. Our results showed that in the prefrontal cortex and hippocampus of the diabetes group, oxidative stress parameters, pro-inflammatory cytokines, apoptosis and, blood glucose levels were increased, while antioxidant and anti-inflammatory cytokines were diminished compared to the control group. However, HN treatment was able to modulate these markers, including blood glucose and the markers of oxidative stress, inflammation, and apoptosis. In conclusion, our findings suggest that hyperglycemia, oxidative stress, inflammation, and apoptosis may contribute to the development of diabetes-induced cognitive impairments. By regulating these changes with HN treatment, we may be able to positively contribute to the treatment of cognitive impairments induced by diabetes.

Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; Blood Glucose; Cytokines; Diabetes Mellitus; Inflammation; Mice; Oxidative Stress

Pancreatic beta-cell apoptosis is important in the pathogenesis and potential treatment of type 1 diabetes mellitus. We investigated whether Humanin, a recently described survival factor for neurons, could improve the survival of beta-cells and delay or treat diabetes in the nonobese diabetic (NOD) model. Humanin reduced apoptosis induced by serum starvation in NIT-1 cells and decreased apoptosis induced by cytokine treatment. Humanin induced signal transducer and activator of transcription 3 and extracellular signal-regulated kinase phosphorylation over a 24-hour time course. Specific inhibition of signal transducer and activator of transcription 3 resulted in nullifying the protective effect of Humanin. Humanin normalized glucose tolerance in NOD mice treated for 6 weeks, and their pancreata revealed decreased lymphocyte infiltration and severity. In addition, Humanin delayed/prevented the onset of diabetes in NOD mice treated for 20 weeks. In summary, Humanin treatment decreases cytokine-induced apoptosis in beta-cells in vitro and improved glucose tolerance and onset of diabetes in NOD mice in vivo. This indicates that Humanin may be useful for islet protection and survival in a spectrum of diabetes-related therapeutics.

Topics: Animals; Apoptosis; Caspases; Diabetes Mellitus; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Extracellular Signal-Regulated MAP Kinases; Female; Glucose Tolerance Test; Immunoblotting; Immunohistochemistry; Insulin-Secreting Cells; Intracellular Signaling Peptides and Proteins; Mice; Mice, Inbred NOD; Neurons; Neurosecretory Systems; STAT3 Transcription Factor

Topics: Administration, Intranasal; Alzheimer Disease; Animals; Diabetes Mellitus; Drug Delivery Systems; Drug Design; Fibroblast Growth Factors; Humans; Intracellular Signaling Peptides and Proteins; Osteoporosis; Parathyroid Hormone; Peptide Fragments; Peptides; Proteins; Psoriasis