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Diabetes/metabolism Research and Reviews Mar 2023Hyperglucagonemia is one of the 'ominous' eight factors underlying the pathogenesis of type 2 diabetes (T2D). Glucagon is a peptide hormone involved in maintaining... (Review)
Review
Hyperglucagonemia is one of the 'ominous' eight factors underlying the pathogenesis of type 2 diabetes (T2D). Glucagon is a peptide hormone involved in maintaining glucose homoeostasis by increasing hepatic glucose output to counterbalance insulin action. Long neglected, the introduction of dual and triple agonists exploiting glucagon signalling pathways has rekindled the interest in this hormone beyond its classic effect on glycaemia. Glucagon can promote weight loss by regulating food intake, energy expenditure, and brown and white adipose tissue functions through mechanisms still to be fully elucidated, thus its role in T2D pathogenesis should be further investigated. Moreover, the role of glucagon in the development of T2D micro- and macro-vascular complications is elusive. Mounting evidence suggests its beneficial effect in non-alcoholic fatty liver disease, while few studies postulated its favourable role in peripheral neuropathy and retinopathy. Contrarily, glucagon receptor agonism might induce renal changes resembling diabetic nephropathy, and data concerning glucagon actions on the cardiovascular system are conflicting. This review aims to summarise the available findings on the role of glucagon in the pathogenesis of T2D and its complications. Further experimental and clinical data are warranted to better understand the implications of glucagon signalling modulation with new antidiabetic drugs.
Topics: Humans; Glucagon; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Non-alcoholic Fatty Liver Disease; Glucose; Glucagon-Like Peptide-1 Receptor
PubMed: 36637256
DOI: 10.1002/dmrr.3609 -
Phytomedicine : International Journal... Sep 2018Pathological pain conditions can be triggered after peripheral nerve injury and/or inflammation. It is a major clinical problem that is poorly treated with available... (Review)
Review
BACKGROUND
Pathological pain conditions can be triggered after peripheral nerve injury and/or inflammation. It is a major clinical problem that is poorly treated with available therapeutics. Curcumin is a phenolic compound derived from Curcuma longa, being widely used for its antioxidant, anti-inflammatory and immunomodulatory effects.
PURPOSE
This review systematically summarized updated information on the traditional uses of curcumin in order to explore antinociceptive effects in pathological pain and evaluate future therapeutic opportunities clinically. Moreover, some structure-activity relationships would greatly enrich the opportunity of finding new and promising lead compounds and promote the reasonable development of curcumin.
METHODS
PubMed were searched and the literature from the year 1976 to January 2018 was retrieved using keywords pain and curcumin.
RESULTS
This review systematically summarized updated information on the traditional uses, chemical constituents and bioactivities of curcumin, and highlights the recent development of the mechanisms of curcumin in the pathological pain by sciatic nerve injury, spinal cord injury, diabetic neuropathy, alcoholic neuropathy, chemotherapy induced peripheral neuroinflammtion, complete Freund's adjuvant (CFA) injection or carrageenan injection. Importantly, the clinical studies provide a compelling justification for its use as a dietary adjunct for pain relief. And we also present multiple approaches to improve bioavailability of curcumin for the treatment of pathological pain.
CONCLUSION
This review focuses on pre-clinical and clinical studies in the treatment of pathological pain. Although the mechanisms of pain mitigating effects are not very clear, there is compelling evidence proved that curcumin plays an essential role. However, further high-quality clinical studies should be undertaken to establish the clinical effectiveness of curcumin in patients suffering from pathological pain. Potential methods of increase the water solubility and bioavailability of curcumin still need to be studied. These approaches will help in establishing it as remedy for pathological pain.
Topics: Analgesics; Animals; Curcumin; Humans; Pain; Pain Measurement
PubMed: 30195871
DOI: 10.1016/j.phymed.2018.04.045 -
Cureus Sep 2021Diabetes mellitus (DM) is a chronic metabolic disorder with a multi-systemic involvement, the gastrointestinal (GI) system being one of them. In this study, we have... (Review)
Review
Diabetes mellitus (DM) is a chronic metabolic disorder with a multi-systemic involvement, the gastrointestinal (GI) system being one of them. In this study, we have compiled and analyzed findings from various studies to conclude that peripheral insulin resistance and hyperglycemia are the two key factors that play a role in the pathogenesis of the web of disorders associated with diabetes. These two key factors, when clubbed with autoimmunity, autonomic neuropathy, and genetic and environmental factors, play a substantial role in the development of GI disorders in DM. This article examines GI disorders such as gastric autonomic neuropathy, non-alcoholic fatty liver disease (NAFLD), celiac disease (CD), etc. It also highlights the importance of regular screening and assessment of DM in preventing the GI tangent of the disease. A prompt blood glucose control through lifestyle modifications, dietary management, and weight reduction, coupled with pharmacotherapy for existing DM, can lead to a better outcome and an optimistic perspective on the disease.
PubMed: 34712528
DOI: 10.7759/cureus.18245 -
BioFactors (Oxford, England) Jul 2021The present demographic changes toward an aging society caused a rise in the number of senior citizens and the incidence and burden of age-related diseases (such as... (Review)
Review
The present demographic changes toward an aging society caused a rise in the number of senior citizens and the incidence and burden of age-related diseases (such as cardiovascular diseases [CVD], cancer, nonalcoholic fatty liver disease [NAFLD], diabetes mellitus, and dementia), of which nearly half is attributable to the population ≥60 years of age. Deficiencies in individual nutrients have been associated with increased risks for age-related diseases and high intakes and/or blood concentrations with risk reduction. Nutrition in general and the dietary intake of essential and nonessential biofactors is a major determinant of human health, the risk to develop age-related diseases, and ultimately of mortality in the older population. These biofactors can be a cost-effective strategy to prevent or, in some cases, even treat age-related diseases. Examples reviewed herein include omega-3 fatty acids and dietary fiber for the prevention of CVD, α-tocopherol (vitamin E) for the treatment of biopsy-proven nonalcoholic steatohepatitis, vitamin D for the prevention of neurodegenerative diseases, thiamine and α-lipoic acid for the treatment of diabetic neuropathy, and the role of folate in cancer epigenetics. This list of potentially helpful biofactors in the prevention and treatment of age-related diseases, however, is not exhaustive and many more examples exist. Furthermore, since there is currently no generally accepted definition of the term biofactors, we here propose a definition that, when adopted by scientists, will enable a harmonization and consistent use of the term in the scientific literature.
Topics: Aged; Cardiovascular Diseases; Dementia; Diabetes Mellitus; Dietary Fiber; Dietary Supplements; Epigenesis, Genetic; Fatty Acids, Omega-3; Folic Acid; Humans; Neoplasms; Non-alcoholic Fatty Liver Disease; Thiamine; Thioctic Acid; Vitamin D; Vitamin E
PubMed: 33772908
DOI: 10.1002/biof.1728 -
Frontiers in Endocrinology 2023To investigate the association between non-alcoholic fatty liver disease (NAFLD) and liver enzymes with the incidence of microvascular complications (neuropathy,...
OBJECTIVE
To investigate the association between non-alcoholic fatty liver disease (NAFLD) and liver enzymes with the incidence of microvascular complications (neuropathy, retinopathy, and nephropathy) in a cohort of Iranian patients with type 2 diabetes.
METHODS
For a total population of 3123 patients with type 2 diabetes, a prospective study was designed for 1215 patients with NAFLD and 1908 gender and age-matched control patients without NAFLD. The two groups were followed for a median duration of 5 years for the incidence of microvascular complications. The association between having NAFLD, the level of liver enzymes, aspartate aminotransferase to platelet ratio index (APRI), Fibrosis-4 (FIB-4) value, and the incidence risk of diabetic retinopathy, neuropathy, and nephropathy were assessed through logistic regression analysis.
RESULTS
NAFLD was found to be associated with incidence of diabetic neuropathy and nephropathy (Odds ratio: 1.338 (95% confidence interval: 1.091-1.640) and 1.333 (1.007-1.764), respectively). Alkaline-phosphatase enzyme was found to be associated with higher risks of diabetic neuropathy and nephropathy ((Risk estimate: 1.002 (95% CI: 1.001-1.003) and 1.002 (1.001-1.004), respectively)). Moreover, gamma-glutamyl transferase was associated with a higher risk of diabetic nephropathy (1.006 (1.002-1.009). Aspartate aminotransferase and alanine aminotransferase were inversely associated with the risk of diabetic retinopathy (0.989 (0.979-0.998) and 0.990 (0.983-0.996), respectively). Furthermore, ARPI_T (1), ARPI_T (2), and ARPI_T (3) were shown to be associated with NAFLD (1.440 (1.061-1.954), 1.589 (1.163-2.171), and 2.673 (1.925, 3.710), respectively). However, FIB-4 score was not significantly associated with risk of microvascular complications.
CONCLUSION
Despite the benign nature of NAFLD, patients with type 2 diabetes should be always assessed for NAFLD to ensure early diagnosis and entry into proper medical care. Regular screenings of microvascular complications of diabetes is also suggested for these patients.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Prospective Studies; Diabetic Retinopathy; Diabetic Neuropathies; Risk Factors; Incidence; Iran; Aspartate Aminotransferases
PubMed: 37342261
DOI: 10.3389/fendo.2023.1147458 -
Journal of Clinical and Experimental... 2019Small intestinal bacterial overgrowth (SIBO) is defined by increased density and/or abnormal composition of microbiota in the small bowel. SIBO is often encountered in... (Review)
Review
Small intestinal bacterial overgrowth (SIBO) is defined by increased density and/or abnormal composition of microbiota in the small bowel. SIBO is often encountered in patients with cirrhosis as a result of impaired intestinal motility and delayed transit time, both of which are exacerbated by more severe liver disease. Additional risk factors for SIBO commonly encountered in cirrhotic patients include coexisting diabetes, autonomic neuropathy, and/or alcoholic use. Diagnosis of SIBO is performed by breath testing or jejunal aspiration, the gold standard. In cirrhotic patients, the presence of SIBO can lead to profound clinical consequences. Increased intestinal permeability in these patients predisposes to bacterial translocation into the systemic circulation. As a result, SIBO is implicated as a significant risk factor in the pathogenesis of both spontaneous bacterial peritonitis and hepatic encephalopathy in cirrhotics. Antibiotics, especially rifaximin, are the best studied and most effective treatment options for SIBO. However, prokinetics, probiotics, nonselective beta-blockers, and treatment of underlying liver-related pathophysiology with transjugular intrahepatic portosystemic shunt placement or liver transplantation are also being investigated. This review will discuss the risk factors, diagnosis, manifestations in cirrhosis, and treatment options of SIBO.
PubMed: 31024208
DOI: 10.1016/j.jceh.2018.08.006 -
Annals of Translational Medicine Apr 2019The understanding and management of Wilson disease (WD) have dramatically improved since the first description of the disease by K. Wilson more than a century ago.... (Review)
Review
The understanding and management of Wilson disease (WD) have dramatically improved since the first description of the disease by K. Wilson more than a century ago. However, the persistent long delay between the first symptoms and diagnosis emphasizes challenges in diagnosing earlier this copper overload disorder. As a treatable disease, WD should be detected early in the course of the disease by any health professionals at any care level, but the rare prevalence of the disease explains the lack of awareness of referring physicians. The most important challenge is to train physicians to recognize atypical or rare symptoms of WD that will lead to discuss the diagnosis more systematically. Atypia can come from the age of onset, the liver [non-alcoholic steatohepatitis (NASH) presentation], the central or peripheral nervous system (neuropathy, epilepsy, sleep disorders…) or may be due to lesions of other organs (renal manifestations, osteo-articular disorders or endocrine disturbances). Isolated biological anomalies, rare radiological findings or inadequate interpretation of copper test may also lead to misdiagnosis. The second challenge is to confirm the diagnosis faster and more effectively so as not to delay the initiation of treatment, and expand family screening as the genetic prevalence is higher than previously expected. Generalization of the exchangeable copper assay and the next generation sequencing (NGS) are two promising ways to overcome this ultimate challenge. By drawing attention to the earliest and rare symptoms and to new biomarkers and diagnostic tools, we hope that this article will increase diagnostic awareness and reduce delays so that patients can start their treatment earlier in the course of the illness and thus have a better disease prognosis.
PubMed: 31179304
DOI: 10.21037/atm.2019.02.10 -
Bone Nov 2023Multiple pathogenetic mechanisms are involved in the genesis of various microvascular and macrovascular complications of diabetes mellitus. Of all these, advanced... (Review)
Review
BACKGROUND
Multiple pathogenetic mechanisms are involved in the genesis of various microvascular and macrovascular complications of diabetes mellitus. Of all these, advanced glycation end products (AGEs) have been strongly implicated.
OBJECTIVES
The present narrative review aims to summarize the available literature on the genesis of AGEs and their potential role in the causation of both micro- and macrovascular complications of diabetes mellitus.
RESULTS
Uncontrolled hyperglycemia triggers the formation of AGEs through non-enzymatic glycation reactions between reducing sugars and proteins, lipids, or nucleic acids. AGEs accumulate in bloodstream and bodily tissues under chronic hyperglycemia. AGEs create irreversible cross-linkages of various intra- and extracellular molecules and activate the receptor for advanced glycation end products (RAGE), which stimulates downstream signaling pathways that generate reactive oxygen species (ROS) and contribute to oxidative stress. Additionally, intracellular glycation of mitochondrial respiratory chain proteins by AGEs contributes to the further generation of ROS, which, in turn, sets a vicious cycle that further promotes the production of endogenous AGEs. Through these pathways, AGEs play a principal role in the pathogenesis of various diabetic complications, including diabetic retinopathy, nephropathy, neuropathy, bone disease, atherosclerosis and non-alcoholic fatty liver disease. Multiple clinical studies and meta-analyses have revealed a positive association between tissue or circulating levels of AGEs and development of various diabetic complications. Besides, exogenous AGEs, primarily those derived from diets, promote insulin resistance, obesity, and metabolic syndrome.
CONCLUSIONS
AGEs, triggered by chronic hyperglycemia, play a pivotal role in the pathogenesis of various complications of diabetes mellitus.
Topics: Humans; Metabolic Syndrome; Glycemic Control; Reactive Oxygen Species; Hyperglycemia; Cardiovascular Diseases; Glycation End Products, Advanced
PubMed: 37598920
DOI: 10.1016/j.bone.2023.116884 -
Archives of Pharmacal Research Jul 2021Diabetes mellitus, a disorder of metabolism, results in the elevation of glucose level in the blood. In this hyperglycaemic condition, aldose reductase overexpresses and... (Review)
Review
Diabetes mellitus, a disorder of metabolism, results in the elevation of glucose level in the blood. In this hyperglycaemic condition, aldose reductase overexpresses and leads to further complications of diabetes through the polyol pathway. Glucose metabolism-related disorders are the accumulation of sorbitol, overproduction of NADH and fructose, reduction in NAD, and excessive NADPH usage, leading to diabetic pathogenesis and its complications such as retinopathy, neuropathy, and nephropathy. Accumulation of sorbitol results in the alteration of osmotic pressure and leads to osmotic stress. The overproduction of NADH causes an increase in reactive oxygen species production which leads to oxidative stress. The overproduction of fructose causes cell death and non-alcoholic fatty liver disease. Apart from these disorders, many other complications have also been discussed in the literature. Therefore, the article overviews the aldose reductase as the causative agent and a potential target for the treatment of diabetic complications. So, aldose reductase inhibitors have gained much importance worldwide right now. Several inhibitors, like derivatives of carboxylic acid, spirohydantoin, phenolic derivatives, etc. could prevent diabetic complications are discussed in this article.
Topics: Aldehyde Reductase; Animals; Blood Glucose; Diabetes Complications; Disease Models, Animal; Enzyme Inhibitors; Humans; Molecular Targeted Therapy
PubMed: 34279787
DOI: 10.1007/s12272-021-01343-5 -
Diabetes Therapy : Research, Treatment... Dec 2021Pentoxifylline (Px) has protean effects that can be utilized in the therapy of diabetes and its complications. There have been well-documented but often inconclusive... (Review)
Review
Pentoxifylline (Px) has protean effects that can be utilized in the therapy of diabetes and its complications. There have been well-documented but often inconclusive improvements in peripheral arterial disease, foot ulcers, peripheral neuropathy, nephropathy, retinopathy, ischemic heart disease and cerebrovascular disease. In addition, non-alcoholic steatosis and steatohepatitis, which are closely associated with insulin resistance and type 2 diabetes, have been shown to improve with pentoxifylline. Surprisingly, pentoxifylline modestly improves insulin resistance through improvements in capillary blood flow as well as beta cell function and decreased hepatic glucose production. The therapeutic effects of pentoxifylline are complementary to the effects of drugs such as blockers of the renin-angiotensin-aldosterone system when utilized in the therapy of diabetic nephropathy.
PubMed: 34647189
DOI: 10.1007/s13300-021-01168-x