A comprehensive account of insulin and LDL receptor activity over the years: A highlight on their signaling and functional role.

Insulin receptor (IR) was discovered in 1970. Shortcomings in IR transcribed signals were found pro-diabetic, which could also inter-relate obesity and atherosclerosis in a time-dependent manner. Low-density lipoprotein receptor (LDLR) was discovered in 1974. Later studies showed that insulin could modulate LDLR expression and activity. Repression of LDLR transcription in the absence or inactivity of insulin showed a direct cause of atherosclerosis. Leptin receptor (OB-R) was found in 1995 and its resistance became responsible for developing obesity. The three interlinked pathologies namely, diabetes, atherosclerosis, and obesity were later on marked as metabolic syndrome-X (MSX). In 2012, the IR-LDLR inter-association was identified. In 2019, the proficiency of signal transmission from this IR-LDLR receptor complex was reported. LDLR was found to mimic IR-generated signaling path when it remains bound to IR in IR-DLR interlocked state. This was the first time LDLR was found sending messages besides its LDL-clearing activity from blood vessels.

Insulin signaling in health and disease.

The molecular mechanisms of cellular insulin action have been the focus of much investigation since the discovery of the hormone 100 years ago. Insulin action is impaired in metabolic syndrome, a condition known as insulin resistance. The actions of the hormone are initiated by binding to its receptor on the surface of target cells. The receptor is an α2ß2 heterodimer that binds to insulin with high affinity, resulting in the activation of its tyrosine kinase activity. Once activated, the receptor can phosphorylate a number of intracellular substrates that initiate discrete signaling pathways. The tyrosine phosphorylation of some substrates activates phosphatidylinositol-3-kinase (PI3K), which produces polyphosphoinositides that interact with protein kinases, leading to activation of the kinase Akt. Phosphorylation of Shc leads to activation of the Ras/MAP kinase pathway. Phosphorylation of SH2B2 and of Cbl initiates activation of G proteins such as TC10. Activation of Akt and other protein kinases produces phosphorylation of a variety of substrates, including transcription factors, GTPase-activating proteins, and other kinases that control key metabolic events. Among the cellular processes controlled by insulin are vesicle trafficking, activities of metabolic enzymes, transcriptional factors, and degradation of insulin itself. Together these complex processes are coordinated to ensure glucose homeostasis.

Metabolic Syndrome: Past, Present and Future.

Most clinicians and health professionals have heard or read about metabolic syndrome [...].

[The urethra of Napoleon, a conduit towards the end of the Empire?] / L'urètre de Napoléon, un conduit vers la fin de l'Empire.

INTRODUCTION: Napoleon died of a cancer of the stomach. Another assumption can be proposed, that of an uronéphrologique pathology. MATERIAL AND METHOD: It is about a historical study basing on the report of autopsy of Antommarchi and the assumptions formulated according to the urinary and nephrologic symptoms presented during his life. RESULTS: Napoleon presented signs of nephropathy in a probable context of metabolic syndrome and many signs of dysurie early on probable stricture of the urethra related to the intensive practice of horse. CONCLUSION: The urethra of Napoleon led France of the empire to the republic.

Historical perspectives of the metabolic syndrome.

The metabolic syndrome (MetS) or insulin resistance syndrome is a constellation of obesity-related metabolic derangements predisposing to type 2 diabetes and cardiovascular disease. In 1998, WHO defined the first criteria of MetS. Three years later, the user-friendly National Cholesterol Education Program criteria of MetS were proposed. Different criteria were issued by the International Diabetes Federation in 2005, making abdominal obesity a necessary component. Several international societies, including The International Diabetes Federation, jointly adopted the revised National Cholesterol Education Program criteria as harmonizing criteria of MetS in 2009. WHO warned the next year that MetS has limited practical utility as a management tool. Adipose tissue inflammation has been shown to be a fundamental mechanism of metabolic derangements, associated with ectopic lipid deposit and mitochondrial dysfunction in skeletal muscle and the liver.

A History of Bariatric Surgery: The Maturation of a Medical Discipline.

This article examines the progression of bariatric surgery since its creation more than 60 years ago with a focus on the effect of surgery on weight loss, comorbidity reduction, and safety. The success has been remarkable. It is possible to cure severe obesity, type 2 diabetes, and hyperlipidemia in addition to the many other manifestations of the metabolic syndrome with remarkable safety. Equally important are the opportunities for research afforded by the surgery and its outcomes. Until better treatments become available, bariatric surgery is the therapy of choice for patients with morbid obesity for weight control and comorbidity improvement.

Síndrome metabólico en adultos mayores de 40 años en 2 consultorios médicos de familia / Metabolic syndrome in adults over 40 years in 2 medical offices

Introducción: el síndrome metabólico (SM), inicialmente descrito por Reaven en 1988, es una asociación de trastornos metabólicos como la dislipidemia, la obesidad, la hipertensión arterial y la intolerancia a la glucosa. Método: se realizó un estudio descriptivo transversal en el que se incluyeron 239 pacientes. Objetivo: determinar la presencia de síndrome metabólico en los pacientes pertenecientes a dos Consultorios Médicos de Familia del Policlínico Universitario Jimmy Hirtzel, de Bayamo, en el período comprendido desde enero de 2009 hasta noviembre de 2011. Resultados: se estableció el diagnóstico de Síndrome metabólico según los criterios de la The Third Report National Cholesterol Education Program. Del total de la muestra se diagnosticó síndrome metabólico en 38 pacientes, siendo significativa la asociación entre la edad y el número de componentes del síndrome metabólico, no así el sexo, no obstante a que el mayor número de pacientes con síndrome metabólico perteneció al sexo femenino. Los parámetros mayormente asociados con el diagnóstico fueron la tensión arterial, la hipertrigliceridemia y la obesidad abdominal. Conclusiones: no se encontró influencia significativa de los hábitos alimentarios y los niveles de actividad física sobre la aparición de síndrome metabólico(AU)

Introduction: the metabolic syndrome (SM), initially described by Reaven in 1988, is an association of metabolic disorders like dislipidemia, obesity, hypertension and the intolerance to the glucose. Method: it was performed a transversal descriptive study in which there were included 239 patients. Objective: to determine the presence of the metabolic syndrome in the patients belonging to 2 Family Medical Offices from the University Polyclinic Jimmy Hirtzel in Bayamo, during the period between January of 2009 until November of 2011. Results: it was established the diagnostic of metabolic Syndrome according to the criteria of the Third Report National Cholesterol Education Program. From the amount of the sample it was diagnosed the metabolic syndrome in 38 patients, being significant the association between the age and the number of components of the metabolic syndrome, unlike the sex. Nevertheless, the greatest number of patients with metabolic syndrome belonged to the feminine sex. The parameters mostly associated with the diagnostic were the blood pressure, the hypertriglyceridemia and the abdominal obesity. Conclusions: it was not found a significant influence in the alimentary habits and the levels of physical activity about the emergence of the metabolic syndrome(EU)

[Gluttony, obesity and the metabolic syndrome in the context of the "seven deadly sins". Historical-theological, literary and art, mass media, political, philosophical, medical-psychological and geriatric aspects of the problem].

In this pape different aspects of problem of obesity are analysed.

Diffuse idiopathic skeletal hyperostosis: diagnosis in a palaeopathological context.

Clinically, the presence of diffuse idiopathic skeletal hyperostosis (DISH) has been linked to a disturbance of glucose and insulin metabolism, hypertension, dyslipidemia and obesity associated with a rich diet. The prevalence of DISH in archaeological skeletal samples may therefore be a valuable indicator of their socio-economic status when compared to other contemporary groups. However, various methods are currently being used to diagnose DISH. The purpose of this study was therefore to assess the comparability of results obtained using four different diagnostic methods to estimate the prevalence of DISH in a skeletal sample, and to discuss the implications of the results in relation to palaeopathological health assessments. Four different diagnostic criteria were applied to 127 male and 113 female skeletons to diagnose DISH. Skeletal remains were obtained from two 16th century samples from Delft and one modern sample from the anatomy dissection hall of the Leiden University Medical Centre. The estimated prevalences were statistically compared. Special attention was also given to the distribution of extra-spinal enthesophytes described in diagnostic criteria, in order to assess their diagnostic value. The prevalence of DISH observed in the skeletal samples varied significantly depending on the criteria used for diagnosis. Furthermore, extra-spinal enthesophytes, suggested as being indicative of DISH, proved to be variable and unreliable. It was concluded that it is of great importance to explicitly state and adhere to criteria employed for diagnosing DISH in both palaeopathological and clinical investigations in order to ensure reliable comparisons between studies. Also, DISH cannot be positively diagnosed solely based on the presence of extra-spinal enthesophytes.

Metabolic syndrome: its history, mechanisms, and limitations.

In late twentieth century, Ruderman and Reaven showed that insulin resistance might be fundamental to metabolic syndrome (MetS) which means a constellation of obesity-related metabolic derangements predisposing to type 2 diabetes and cardiovascular disease. In 2001, user-friendly National Cholesterol Education Program (NCEP) criteria of MetS were proposed. In 2005, the International Diabetes Federation (IDF) and the Examination Committee for Criteria of Metabolic Syndrome in Japan issued different criteria of MetS where abdominal obesity is a necessary component. In 2009, IDF, National Heart, Lung, and Blood Institute, American Heart Association, World Heart Federation, International Atherosclerosis Society, and International Association for the Study of Obesity jointly adopted the revised NCEP criteria, where abdominal obesity is not a necessary component, as worldwide criteria of MetS. In 2010, WHO Expert Consultation warned that MetS is a concept that focuses attention on complex multifactorial health problems but has limited practical utility as a management tool. In animal studies, adipose tissue inflammation characterized by an increased number of crown-like structures in adipose tissue, rather than obesity per se, was shown to be a fundamental mechanism of metabolic derangements.

The inflammasome: in memory of Dr. Jurg Tschopp.

A decade ago, Jurg Tschopp introduced the concept of the inflammasome. This exciting discovery of a macromolecular complex that senses 'danger' and initiates the inflammatory response contributed to a renaissance in the fields of innate immunity and cell death. Jurg led the biochemical characterization of the inflammasome complex and demonstrated that spontaneous hyperactivation of this interleukin (IL)-1ß processing machinery is the molecular basis of a spectrum of hereditary periodic fever syndromes, caused by mutated forms of the inflammasome scaffolding receptor, NLRP3. The identification of the underlying mechanism in these disorders has led to their now successful therapy, with the use of the IL-1 receptor antagonist in the clinic. Jurg's pioneering work has subsequently defined a number of inflammasome agonists ranging from microbial molecules expressed during infection, to triggers of sterile inflammation, most notably gout-associated uric acid crystals, asbestos, silica and nanoparticles. More recently, Jurg introduced the critical new concept of the metabolic inflammasome, which senses metabolic stress and contributes to the onset of the metabolic syndrome associated with obesity and type 2 diabetes. Jurg was an outstanding and skillful biochemist, an elegant and rigorous researcher often far ahead of his peers. He was a truly amiable person, fair, generous and inspiring, and will be most remembered for his infectious enthusiasm. We write this review article on the inflammasome in his honor and dedicate it to his memory.

[History of diabetology in Lower Silesia]. / Rys historyczny diabetologii na Dolnym Slasku.

The authors presented the history of diabetology in the time before and after the 2nd world war, the outstanding diabetological scientists f.e. professor Minkowski, Stolte, Lublin. Further presented was the actual situation and development of the diabetology in Lower Silesia.

Metabolic syndrome: what are the risks for humans?

Metabolic syndrome (MetS) is a widely prevalent and multi-factorial disorder. The syndrome has been given several names such as insulin resistance (IR) syndrome, plurimetabolic syndrome, Reaven's syndrome, Syndrome X, and the deadly quartet. The formulation of National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP) guidelines has led to some uniformity and standardization of the definition of MetS and has been helpful epidemiologically. The clinical relevance of MetS is related to its role in the development of cardiovascular disease. Weight reduction is one of the mainstays of treatment. This article provides a comprehensive discussion of metabolic risk factors, the history of MetS, and its diagnosis, epidemiology, etiology, pathophysiology, and treatment. There is a need to comprehensively review this particular syndrome in view of the ever increasing-incidence of this condition.

Disease of the Sultans: metabolic syndrome in Ottoman dynasty.

Metabolic syndrome is generally considered as a complication of modernity. Here we searched for the presence of metabolic syndrome components among the Ottoman emperors who lived between 1258 and 1926. Collections of historical archives, which were published as books specifically about morbidity and mortality of Ottoman emperors were reviewed to diagnose metabolic syndrome according to modified criteria by American College of Endocrinology and American Association of Clinical Endocrinologists. Nineteen of 36 dynasty members (53%) had fatal or non-fatal cardiovascular events. Twenty-nine of the dynasty (81%) members were either depicted as truncal obese or reported to have obesity. Thirteen emperors (36%) satisfied diagnostic criteria for metabolic syndrome, retrospectively. Overall, 42% of non-commanding emperors, but 26% of commanding-emperors (who were assumed to be athletically grown and physically more active) were found to have metabolic syndrome (p=0.553). We suggest firstly here that sedentary palace lifestyle exacerbated metabolic syndrome in Ottoman dynasty especially in elderly members, thereafter complicated by cardiovascular events, even in pre-modern era.