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Cells Aug 2021Dysregulation of autophagy is an important underlying cause in the onset and progression of many metabolic diseases, including diabetes. Studies in animal models and... (Review)
Review
Dysregulation of autophagy is an important underlying cause in the onset and progression of many metabolic diseases, including diabetes. Studies in animal models and humans show that impairment in the removal and the recycling of organelles, in particular, contributes to cellular damage, functional failure, and the onset of metabolic diseases. Interestingly, in certain contexts, inhibition of autophagy can be protective. While the inability to upregulate autophagy can play a critical role in the development of diseases, excessive autophagy can also be detrimental, making autophagy an intricately regulated process, the altering of which can adversely affect organismal health. Autophagy is indispensable for maintaining normal cardiac and vascular structure and function. Patients with diabetes are at a higher risk of developing and dying from vascular complications. Autophagy dysregulation is associated with the development of heart failure, many forms of cardiomyopathy, atherosclerosis, myocardial infarction, and microvascular complications in diabetic patients. Here, we review the recent findings on selective autophagy in hyperglycemia and diabetes-associated microvascular and macrovascular complications.
Topics: Animals; Autophagy; Diabetes Complications; Humans; Hyperglycemia; Organelles; Reactive Oxygen Species; Signal Transduction; Vascular Diseases
PubMed: 34440882
DOI: 10.3390/cells10082114 -
Theranostics 2022Diabetes mellitus (DM) is a chronic systemic disease with increasing prevalence globally. An important aspect of diabetic pathogenesis is cellular crosstalk and... (Review)
Review
Diabetes mellitus (DM) is a chronic systemic disease with increasing prevalence globally. An important aspect of diabetic pathogenesis is cellular crosstalk and information exchange between multiple metabolic organs and tissues. In the past decade, increasing evidence suggested that extracellular vesicles (EVs), a class of cell-derived membrane vesicles that transmit information and perform inter-cellular and inter-organ communication, are involved in the pathological changes of insulin resistance (IR), inflammation, and endothelial injury, and implicated in the development of DM and its complications. The biogenesis and cargo sorting machinery dysregulation of EVs may mediate their pathogenic roles under diabetic conditions. Moreover, the biogenesis of EVs, their ubiquitous production by different cells, their function as mediators of inter-organ communication, and their biological features in body fluids have generated great promise as biomarkers and clinical treatments. In this review, we summarize the components of EV generation and sorting machinery and highlight their role in the pathogenesis of DM and associated complications. Furthermore, we discuss the emerging clinical implications of EVs as potential biomarkers and therapeutic strategies for DM and diabetic complications. A better understanding of EVs will deepen our knowledge of the pathophysiology of DM and its complications and offer attractive approaches to improve the prevention, diagnosis, treatment, and prognosis of these disorders.
Topics: Biology; Biomarkers; Diabetes Complications; Diabetes Mellitus; Extracellular Vesicles; Humans
PubMed: 35154494
DOI: 10.7150/thno.65778 -
International Journal of Molecular... Dec 2021Diabetes mellitus (DM) leads to complications, the majority of which are nephropathy, retinopathy, and neuropathy. Redox imbalance and inflammation are important... (Review)
Review
Diabetes mellitus (DM) leads to complications, the majority of which are nephropathy, retinopathy, and neuropathy. Redox imbalance and inflammation are important components of the pathophysiology of these complications. Many studies have been conducted to find a specific treatment for these neural complications, and some of them have investigated the therapeutic potential of melatonin (MEL), an anti-inflammatory agent and powerful antioxidant. In the present article, we review studies published over the past 21 years on the therapeutic efficacy of MEL in the treatment of DM-induced neural complications. Reports suggest that there is a real prospect of using MEL as an adjuvant treatment for hypoglycemic agents. However, analysis shows that there is a wide range of approaches regarding the doses used, duration of treatment, and treatment times in relation to the temporal course of DM. This wide range hinders an objective analysis of advances and prospective vision of the paths to be followed for the unequivocal establishment of parameters to be used in an eventual therapeutic validation of MEL in neural complications of DM.
Topics: Animals; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Diabetic Retinopathy; Humans; Melatonin
PubMed: 35008523
DOI: 10.3390/ijms23010100 -
Pharmacology 2022The pathobiology of diabetes and associated complications has been widely researched in various countries, but effective prevention and treatment methods are still... (Review)
Review
BACKGROUND
The pathobiology of diabetes and associated complications has been widely researched in various countries, but effective prevention and treatment methods are still insufficient. Diabetes is a metabolic disorder of carbohydrates, fats, and proteins caused by an absence of insulin or insulin resistance, which mediates an increase of oxidative stress, release of inflammatory factors, and macro- or micro-circulation dysfunctions, ultimately developing into diverse complications.
SUMMARY
In the last decade through pathogenesis research, epigenetics has been found to affect metabolic diseases. Particularly, DNA methylation, histone acetylation, and miRNAs promote or inhibit diabetes and complications by regulating the expression of related factors. Curcumin has a wide range of beneficial pharmacological activities, including anti-inflammatory, anti-oxidation, anticancer, anti-diabetes, anti-rheumatism, and increased immunity. Key Messages: In this review, we discuss the effects of curcumin and analogs on diabetes and associated complications through epigenetics, and we summarize the preclinical and clinical researches for curcumin and its analogs in terms of management of diabetes and associated complications, which may provide an insight into the development of targeted therapy of endocrine diseases.
Topics: Acetylation; Animals; Curcumin; DNA Methylation; Diabetes Complications; Diabetes Mellitus; Epigenesis, Genetic; Humans; MicroRNAs
PubMed: 34915505
DOI: 10.1159/000520311 -
Diabetologia Jun 2020Diabetes is one of the most challenging health concerns facing society. Available drugs treat the symptoms but there is no cure. This presents an urgent need to better... (Review)
Review
Diabetes is one of the most challenging health concerns facing society. Available drugs treat the symptoms but there is no cure. This presents an urgent need to better understand human diabetes in order to develop improved treatments or target remission. New disease models need to be developed that more accurately describe the pathology of diabetes. Organoid technology provides an opportunity to fill this knowledge gap. Organoids are 3D structures, established from pluripotent stem cells or adult stem/progenitor cells, that recapitulate key aspects of the in vivo tissues they mimic. In this review we briefly introduce organoids and their benefits; we focus on organoids generated from tissues important for glucose homeostasis and tissues associated with diabetic complications. We hope this review serves as a touchstone to demonstrate how organoid technology extends the research toolbox and can deliver a step change of discovery in the field of diabetes.
Topics: Animals; Diabetes Complications; Diabetes Mellitus; Disease Models, Animal; Humans; Obesity; Organoids; Pluripotent Stem Cells
PubMed: 32221645
DOI: 10.1007/s00125-020-05126-3 -
Advanced Drug Delivery Reviews May 2021Cardiomyopathy and fibrosis are the main causes of heart failure in diabetes patients. For therapeutic purposes, a delivery system is required to enhance antidiabetic... (Review)
Review
Cardiomyopathy and fibrosis are the main causes of heart failure in diabetes patients. For therapeutic purposes, a delivery system is required to enhance antidiabetic drug efficacy and specifically target profibrotic pathways in cardiomyocytes. Nanoparticles (NPs) have distinct advantages, including biocompatibility, bioavailability, targeting efficiency, and minimal toxicity, which make them ideal for antidiabetic treatment. In this review, we overview the latest information on the pathogenesis of cardiomyopathy and fibrosis in diabetes patients. We summarize how NP applications improve insulin and liraglutide efficacy and their sustained release upon oral administration. We provide a comprehensive review of the results of NP clinical trials in diabetes patients and of animal studies investigating the effects of NP-mediated anti-fibrotic treatments. Collectively, the application of advanced NP delivery systems in the treatment of cardiomyopathy and fibrosis in diabetes patients is a promising and innovative therapeutic strategy.
Topics: Animals; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Drug Delivery Systems; Fibrosis; Heart Failure; Humans; Hypoglycemic Agents; Myocytes, Cardiac; Nanoparticles
PubMed: 33417981
DOI: 10.1016/j.addr.2021.01.004 -
International Journal of Molecular... Jun 2021Aortic stenosis (AS) and diabetes mellitus (DM) are both progressive diseases that if left untreated, result in significant morbidity and mortality. Several studies... (Review)
Review
Aortic stenosis (AS) and diabetes mellitus (DM) are both progressive diseases that if left untreated, result in significant morbidity and mortality. Several studies revealed that the prevalence of DM is substantially higher in patients with AS and, thus, the progression from mild to severe AS is greater in those patients with DM. DM and common comorbidities associated with both diseases, DM and AS, increase patient management complexity and make aortic valve replacement the only effective treatment. For that reason, a better understanding of the pathogenesis underlying both these diseases and the relationships between them is necessary to design more appropriate preventive and therapeutic approaches. In this review, we provided an overview of the main aspects of the relationship between AS and DM, including common comorbidities and risk factors. We also discuss the established treatments/therapies in patients with AS and DM.
Topics: Aortic Valve Stenosis; Diabetes Complications; Humans; Risk Factors
PubMed: 34207517
DOI: 10.3390/ijms22126212 -
Diabetes Mar 2020The results of the Diabetes Control and Complications Trial (DCCT) have given rise to much encouragement in the battle to stave off the complications of type 1 diabetes,... (Review)
Review
The results of the Diabetes Control and Complications Trial (DCCT) have given rise to much encouragement in the battle to stave off the complications of type 1 diabetes, showing dramatic declines in the development of severe retinopathy, nephropathy, and neuropathy in those treated intensively compared with conventional therapy. Particularly encouraging has been the continuing difference between the two groups despite both having similar HbA (∼8%) since the end of DCCT, when 96% of participants entered the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. This continuing relative benefit has been termed "metabolic memory," which implies altered metabolic regulation. Based on evidence from both the Epidemiology of Diabetes Complications (EDC) prospective cohort study of childhood-onset type 1 diabetes and DCCT/EDIC, we show that the metabolic memory effect can be largely explained by lower cumulative glycemic exposure in the intensive therapy group, and, on average, the development of complications increases with greater glycemic exposure, irrespective of whether this results from a high exposure for a short time or a lower exposure for a longer time. Thus, there is no need for a concept like "metabolic memory" to explain these observations. Potential mechanisms explaining the cumulative glycemic effect are also briefly discussed.
Topics: Blood Glucose; Cohort Studies; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Patient Care Planning; Prospective Studies; Randomized Controlled Trials as Topic; Time Factors
PubMed: 32079705
DOI: 10.2337/db19-0514 -
Journal of Diabetes Research 2019Diabetes, a metabolic disorder characterized by elevated fasting blood glucose levels, affects nearly 8% of the world population and was predicted that it would be the... (Review)
Review
Diabetes, a metabolic disorder characterized by elevated fasting blood glucose levels, affects nearly 8% of the world population and was predicted that it would be the top seven leading cause of death in the next ten years. The incidence of diabetes and its morbidity are increasing rapidly in developing countries due to lifestyle change and intake of high-calorie diet occurring with urbanization. Medicinal plants and their products have been proven to be effective, less expensive, and safe for the treatment and prevention of diabetes. Although several medicinal plants known for the antidiabetic property are reported in the ancient medical textbook, there is always a scope to identify and validate less explored medicinal plants that are still practiced regularly by local and tribal people since ancient times. Here, in the present article, we would like to review a less explored medicinal plant, , which has promising effects in treating diabetes and other diabetic-associated complications. In spite of its wide use in the Northeast region of India as traditional medicine, there is only one clinical study where the antidiabetic potential of the fruit powder has been shown. Further well-designed animal and human studies are needed to confirm the role of in diabetes and its associated complications.
Topics: Animals; Diabetes Complications; Diabetes Mellitus; Dilleniaceae; Humans; Hypoglycemic Agents; Phytotherapy; Plant Extracts; Treatment Outcome
PubMed: 31871947
DOI: 10.1155/2019/4632491 -
Cell Death & Disease Aug 2019Rapamycin (Sirolimus) slows aging, extends life span, and prevents age-related diseases, including diabetic complications such as retinopathy. Puzzlingly, rapamycin can... (Review)
Review
Rapamycin (Sirolimus) slows aging, extends life span, and prevents age-related diseases, including diabetic complications such as retinopathy. Puzzlingly, rapamycin can induce insulin sensitivity, but may also induce insulin resistance or glucose intolerance without insulin resistance. This mirrors the effect of fasting and very low calorie diets, which improve insulin sensitivity and reverse type 2 diabetes, but also can cause a form of glucose intolerance known as benevolent pseudo-diabetes. There is no indication that starvation (benevolent) pseudo-diabetes is detrimental. By contrast, it is associated with better health and life extension. In transplant patients, a weak association between rapamycin/everolimus use and hyperglycemia is mostly due to a drug interaction with calcineurin inhibitors. When it occurs in cancer patients, the hyperglycemia is mild and reversible. No hyperglycemic effects of rapamycin/everolimus have been detected in healthy people. For antiaging purposes, rapamycin/everolimus can be administrated intermittently (e.g., once a week) in combination with intermittent carbohydrate restriction, physical exercise, and metformin.
Topics: Animals; Diabetes Complications; Fasting; Glucose Intolerance; Humans; Insulin Resistance; Kidney Transplantation; Sirolimus
PubMed: 31406105
DOI: 10.1038/s41419-019-1822-8