SGLT-2 Inhibitors as Calorie Restriction Mimetics

SGLT-2 inhibitors, or gliflozins, are a newer and still expensive class of anti-diabetic drug. They work by interfering in the trafficking of glucose, preventing the kidney from reclaiming glucose and introducing it back into the bloodstream. The glucose is instead excreted. Analogously to metformin, another anti-diabetic drug, it is proposed that inhibition of SGLT-2 in some ways mimic the effects of calorie restriction, triggering beneficial cellular housekeeping mechanisms that usually only turn on during periods of fasting or low calorie intake. Size of effect and degree of side-effects are always the questions in these matters, however. One should hold back any nascent enthusiasm until able to find reliable answers in the literature. Evidently, a faction of the research community thinks that metformin has a large enough effect size to run a human trial versus aging, in order to push the FDA into accepting aging as an indication. Following that same line of thinking, these researchers would probably also consider this strategy for one or more SGLT-2 inhibitors. That said, one of the points of using metformin as the lever, to try to make the FDA reconsider aging as a medical condition that can be treated, is that metformin is very widely used and has a long history of use. Not that it is particularly effective in the grand scheme of things. It is hard for the FDA to object to it on any grounds other than aging not being a formally defined and approved medical condit...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs

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AbstractThe World Health Organization defines overweight and obesity as the condition where excess or abnormal fat accumulation increases risks to health. The prevalence of obesity is increasing worldwide and is around 20% in ICU patients. Adipose tissue is highly metabolically active, and especially visceral adipose tissue has a deleterious adipocyte secretory profile resulting in insulin resistance and a chronic low-grade inflammatory and procoagulant state. Obesity is strongly linked with chronic diseases such as type 2 diabetes, hypertension, cardiovascular diseases, dyslipidemia, non-alcoholic fatty liver disease, chr...
Source: Intensive Care Medicine - Category: Intensive Care Source Type: research
Metabolic disorders such as insulin resistance, obesity, and hyperglycemia are prominent risk factors for the development of non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH). Dietary rodent mod...
Source: BMC Gastroenterology - Category: Gastroenterology Authors: Tags: Research article Source Type: research
This article is protected by copyright. All rights reserved. PMID: 30883738 [PubMed - as supplied by publisher]
Source: The Journal of Physiology - Category: Physiology Authors: Tags: J Physiol Source Type: research
This study provides a possible reason why genes carrying health risks have persisted in human populations. The second found evidence for multiple variants in genes related to ageing that exhibited antagonistic pleiotropic effects. They found higher risk allele frequencies with large effect sizes for late-onset diseases (relative to early-onset diseases) and an excess of variants with antagonistic effects expressed through early and late life diseases. There also exists other recent tangible evidence of antagonistic pleiotropy in specific human genes. The SPATA31 gene has been found under strong positive genomic sele...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Alizai PH, Lurje I, Kroh A, Schmitz S, Luedde T, Andruszkow J, Neumann UP, Ulmer F Abstract Background: More than half of the obese patients develop nonalcoholic fatty liver disease (NAFLD), which may further progress to nonalcoholic steatohepatitis (NASH) and cirrhosis. The aim of this study was to assess alterations in liver function in obese patients with a noninvasive liver function test. Methods: In a prospective cohort study 102 morbidly obese patients undergoing bariatric surgery were evaluated for their liver function. Liver function capacity was determined by the LiMAx® test (enzymatic cap...
Source: Gastroenterology Research and Practice - Category: Gastroenterology Tags: Gastroenterol Res Pract Source Type: research
Publication date: Available online 13 March 2019Source: Journal of Clinical and Experimental HepatologyAuthor(s): Prarthana Thiagarajan, Guruprasad Padur AithalAbstractNon-alcoholic fatty liver disease (NAFLD) is now the leading cause of chronic liver disease in industrialised economies. With no licensed treatment currently available, together with a growing prevalence that parallels global increases in obesity and type 2 diabetes, NAFLD will dominate the landscape of hepatology for the foreseeable future. A multifaceted aetiopathogenesis, paucity of reproducible pre-clinical models that effectively recreate human NAFLD an...
Source: Journal of Clinical and Experimental Hepatology - Category: Gastroenterology Source Type: research
AbstractAimTo investigate whether GE is affected in children/adolescents with obesity and abnormalities of the metabolic syndrome (MetS).MethodsCross-sectional study of oral GE (oGE), insulin sensitivity and secretion (calculated on 5 time-points oral glucose tolerance test) and metabolic abnormalities in 1012 patients with overweight/obesity (aged 6.0 –17.9 years old). A MetS risk score was calculated on the basis of distribution of fasting glucose, triglycerides, HDL-cholesterol, total cholesterol, systolic and diastolic blood pressure. Non-alcoholic fatty liver disease (NAFLD) was suspected based on thresholds of ...
Source: Acta Diabetologica - Category: Endocrinology Source Type: research
AbstractPurpose of ReviewWe review current evidence regarding changes in bile acid (BA) metabolism, transport, and signaling after bariatric surgery and how these might bolster fat mass loss and energy expenditure to promote improvements in type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD).Recent FindingsThe two most common bariatric techniques, Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), increase the size and alter the composition of the circulating BA pool that may then impact energy metabolism through altered activities of BA targets in the many tissues perfused by systemic bl...
Source: Current Obesity Reports - Category: Eating Disorders & Weight Management Source Type: research
Authors: Laursen TL, Hagemann CA, Wei C, Kazankov K, Thomsen KL, Knop FK, Grønbæk H Abstract Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a significant liver disease, and it covers the disease spectrum from simple steatosis with a risk of development of non-alcoholic steatohepatitis (NASH) to fibrosis, subsequent cirrhosis, end-stage liver failure, and liver cancer with a potential need for liver transplantation. NAFLD and NASH are closely related to obesity, metabolic syndrome, and type 2 diabetes (T2D). The role of gut hormones, especially glucagon-like peptide 1 (GLP-1), i...
Source: World Journal of Hepatology - Category: Gastroenterology Tags: World J Hepatol Source Type: research
FINDINGSIn a comprehensive, nine-year-long study in mice, researchers profiled more than 300 liver and plasma lipid species and more than 5,000 liver proteins. The combined data helped researchers to identify new mechanisms that control the metabolism of lipids (molecules that include fat) and to discover a protein that regulates lipids. They found that silencing one particular protein, called PSMD9, is a potential therapeutic strategy to reduce nonalcoholic fatty liver disease.BACKGROUNDNonalcoholic fatty liver disease is the buildup of excess fat in liver cells not caused by alcohol. The disease affects about 25 percent ...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
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