AIM OF THE REVIEW: Rather than a comprehensive coverage of the literature, this article aims to identify discrepancies between findings in animal and human studies, and to highlight some of the problems in developing plant extract-based medicines that lower blood glucose in patients with diabetes, as well as to suggest potential ways forward.
METHODS: In addition to searching the 2018 PubMed literature using the terms 'extract AND blood glucose, a search of the whole literature was conducted using the terms 'plant extracts' AND 'blood glucose' AND 'diabetes' AND 'double blind' with 'clinical trials' as a filter. A third search using PubMed and Medline was undertaken for systematic reviews and meta-analyses investigating the effects of plant extracts on blood glucose/glycosylated haemoglobin in patients with relevant metabolic pathologies.
FINDINGS: Despite numerous animal studies demonstrating the effects of plant extracts on blood glucose, few randomised, double-blind, placebo-controlled trials have been conducted to confirm efficacy in treating humans with diabetes; there have been only a small number of systematic reviews with meta-analyses of clinical studies. Qualitative and quantitative discrepancies between animal and human clinical studies in some cases were marked; the factors contributing to this included variations in the products among different studies, the doses used, differences between animal models and the human disease, and the impact of concomitant therapy in patients, as well as differences in the duration of treatment, and the fact that treatment in animals may begin before or very soon after the induction of diabetes.
CONCLUSION: The potential afforded by natural products has not yet been realised in the context of treating diabetes mellitus. A systematic, coordinated, international effort is required to achieve the goal of providing anti-diabetic treatments derived from medicinal plants.
METHOD: Intriguing evidences discussed the contribution of different intracellular compartments in autophagy membrane formation. Furthermore, autophagy serves to mobilise membranes within cells, thereby promoting cytoplasmic components reorganisation. The intent of this review is to focus on the possibility of autophagy to act as a carrier for GLUT4 through regulating GLUT4 endocytosis, intracellular trafficking in different compartments, and translocation to cell membrane.
RESULTS: The common themes of autophagy and GLUT4 have been highlighted. The review discussed the overlapping of endocytosis mechanism and intracellular compartments, and has shown that autophagy and GLUT4 utilise similar proteins (SNAREs) which are used for exocytosis. On top of that, PI3K and AMPK also control both autophagy and GLUT4.
CONCLUSION: The control of GLUT4 trafficking through autophagy could be a promising field for treating type 2 diabetes.
METHODS: A nanosuspension was prepared using high pressure homogenization (HPH) techniques. The physico-chemical properties of the kaempferol nanosuspension (KNS) were characterized using photon correlation spectroscopy (PCS), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR) and x-ray diffractometry (XRD). A reversephase high performance liquid chromatography (RP-HPLC) method for the analysis of the drug in rat plasma was developed and validated as per ICH guidelines. In vivo pharmacokinetic parameters of oral pure kaempferol solution, oral kaempferol nanosuspension and intravenous pure kaempferol were assessed in rats.
RESULTS AND DISCUSSION: The kaempferol nanosuspension had a greatly reduced particle size (426.3 ± 5.8 nm), compared to that of pure kaempferol (1737 ± 129 nm). The nanosuspension was stable under refrigerated conditions. No changes in physico-chemical characteristics were observed. In comparison to pure kaempferol, kaempferol nanosuspension exhibited a significantly (P<0.05) increased in Cmax and AUC(0-∞) following oral administration and a significant improvement in absolute bioavailability (38.17%) compared with 13.03% for pure kaempferol.
CONCLUSION: These results demonstrate enhanced oral bioavailability of kaempferol when formulated as a nanosuspension.
METHODS: A literature search of studies related to the use of precision medicine in diabetes care was conducted in various databases (PubMed, Google Scholar, and Scopus).
RESULTS: Precision medicine encompasses the integration of a wide array of personal data, including clinical, lifestyle, genetic, and various biomarker information. Its goal is to facilitate tailored treatment approaches using contemporary diagnostic and therapeutic techniques that specifically target patients based on their genetic makeup, molecular markers, phenotypic traits, or psychosocial characteristics. This article not only highlights significant advancements but also addresses key challenges, particularly focusing on the technologies that contribute to the realization of personalized and precise diabetes care.
CONCLUSION: For the successful implementation of precision diabetes medicine, collaboration and coordination among multiple stakeholders are crucial.
AREAS COVERED: Mitochondrial deficits impact insulin-resistant skeletal muscles, adipose tissue, liver, and pancreatic β-cells, affecting glucose and lipid balance. Exercise emerges as a key factor in enhancing mitochondrial function, thereby reducing insulin resistance. Additionally, the therapeutic potential of mitochondrial uncoupling, which generates heat instead of ATP, is discussed. We explore the intricate link between mitochondrial function and diabetes, investigating genetic interventions to mitigate diabetes-related complications. We also cover the impact of insulin deficiency on mitochondrial function, the role of exercise in addressing mitochondrial defects in insulin resistance, and the potential of mitochondrial uncoupling. Furthermore, a comprehensive analysis of Mitochondrial Replacement Therapies (MRT) techniques is presented.
EXPERT OPINION: MRTs hold promise in preventing the transmission of mitochondrial disease. However, addressing ethical, regulatory, and technical considerations is crucial. Integrating mitochondrial-based treatments requires a careful balance between innovation and safety. Ethical dimensions and regulatory aspects of MRT are examined, emphasizing collaborative efforts for the responsible advancement of human health.
METHODS: Diabetes was induced using streptozotocin (60 mg/kg, i.v.) followed by nicotinamide (210 mg/kg, intraperitoneal (i.p.)). MAD (50 mg/kg) was administered orally for 4 weeks, commencing 15 days after induction of diabetes; resveratrol (10 mg/kg) was used as a positive control. Fasting blood glucose, plasma insulin, HbA1c, liver and lipid parameters were measured, along with antioxidant enzymes and malondialdehyde as an index of lipid peroxidation; histological and immunohistochemical studies were also undertaken.
KEY FINDINGS: MAD normalized the elevated fasting blood glucose levels. This was associated with increased plasma insulin concentrations. MAD alleviated oxidative stress by improving enzymatic antioxidants and reducing lipid peroxidation. Histopathological examination showed significant recovery of islet structural degeneration and an increased area of islets. Immunohistochemical staining showed increased insulin content in islets of MAD-treated rats.
CONCLUSIONS: The results demonstrate an antidiabetic effect of MAD associated with preservation of β-cell structure and function.