scholarly journals In appreciation of Sir Philip Randle: The glucose-fatty acid cycle

2007 ◽  
Vol 97 (5) ◽  
pp. 809-813 ◽  
Author(s):  
Mary C. Sugden
Keyword(s):  
Insulin Resistance ◽  
Energy Homeostasis ◽  
Hormone Receptors ◽  
Transcriptional Level ◽  
Acid Cycle ◽  
Fuel Selection ◽  
Regulation Of Metabolism ◽  
Health And Disease ◽  
Glucose Fatty Acid Cycle ◽  
And Storage

The coordinated regulation of metabolic fuel selection is crucial to energy homeostasis. Philip Randle and his colleagues developed the fundamental concept of interplay between carbohydrate and lipid fuels in relation to the requirement for energy utilisation and storage. Their insight has fashioned current understanding of the regulation of metabolism in health and disease, as well as providing a springboard for research into the roles of lipid derivatives in insulin resistance and, at the transcriptional level, lipid-regulated nuclear hormone receptors.

scholarly journals GH replacement causing acute hyperglycaemia and ketonuria in a type 1 diabetic patient

2013 ◽  
Vol 2013 ◽  
Author(s):  
Dominic Cavlan ◽  
Shanti Vijayaraghavan ◽  
Susan Gelding ◽  
William Drake
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Type 1 Diabetes ◽  
Fatty Acid ◽  
Diabetic Patient ◽  
Acid Cycle ◽  
Gh Replacement ◽  
Glucose Fatty Acid Cycle ◽  
Gh Excess

Summary A state of insulin resistance is common to the clinical conditions of both chronic growth hormone (GH) deficiency and GH excess (acromegaly). GH has a physiological role in glucose metabolism in the acute settings of fast and exercise and is the only anabolic hormone secreted in the fasting state. We report the case of a patient in whom knowledge of this aspect of GH physiology was vital to her care. A woman with well-controlled type 1 diabetes mellitus who developed hypopituitarism following the birth of her first child required GH replacement therapy. Hours after the first dose, she developed a rapid metabolic deterioration and awoke with hyperglycaemia and ketonuria. She adjusted her insulin dose accordingly, but the pattern was repeated with each subsequent increase in her dose. Acute GH-induced lipolysis results in an abundance of free fatty acids (FFA); these directly inhibit glucose uptake into muscle, and this can lead to hyperglycaemia. This glucose–fatty acid cycle was first described by Randle et al. in 1963; it is a nutrient-mediated fine control that allows oxidative muscle to switch between glucose and fatty acids as fuel, depending on their availability. We describe the mechanism in detail. Learning points There is a complex interplay between GH and insulin resistance: chronically, both GH excess and deficiency lead to insulin resistance, but there is also an acute mechanism that is less well appreciated by clinicians. GH activates hormone-sensitive lipase to release FFA into the circulation; these may inhibit the uptake of glucose leading to hyperglycaemia and ketosis in the type 1 diabetic patient. The Randle cycle, or glucose–fatty acid cycle, outlines the mechanism for this acute relationship. Monitoring the adequacy of GH replacement in patients with type 1 diabetes is difficult, with IGF1 an unreliable marker.

scholarly journals Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 499
Author(s):  
Kalpana D. Acharya ◽  
Hye L. Noh ◽  
Madeline E. Graham ◽  
Sujin Suk ◽  
Randall H. Friedline ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Glucose Turnover ◽  
Female Mice ◽  
Adult Mice ◽  
Diet Induced Obesity ◽  
Metabolic Dysregulation ◽  
Regulation Of Metabolism ◽  
Junction Protein

A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.

scholarly journals Pharmacological treatment of obesity

2006 ◽  
Vol 50 (2) ◽  
pp. 377-389 ◽  
Author(s):  
Marcio C. Mancini ◽  
Alfredo Halpern
Keyword(s):  
Insulin Resistance ◽  
Pharmacological Treatment ◽  
Energy Homeostasis ◽  
Extensive Review ◽  
Obesity Management ◽  
Physiological Mechanisms ◽  
Triggering Factor ◽  
Treatment Of Obesity ◽  
Obesity Drugs ◽  
Cannabinoid Agonist

This review offers an overview of physiological agents, current therapeutics, as well as medications, which have been extensively used and those agents not currently available or non-classically considered anti-obesity drugs. As obesity - particularly that of central distribution - represents an important triggering factor for insulin resistance, its pharmacological treatment is relevant in the context of metabolic syndrome control. The authors present an extensive review on the criteria for anti-obesity management efficacy, on physiological mechanisms that regulate central and/or peripheral energy homeostasis (nutrients, monoamines, and peptides), on beta-phenethylamine pharmacological derivative agents (fenfluramine, dexfenfluramine, phentermine and sibutramine), tricyclic derivatives (mazindol), phenylpropanolamine derivatives (ephedrin, phenylpropanolamine), phenylpropanolamine oxytrifluorphenyl derivative (fluoxetine), a naftilamine derivative (sertraline) and a lipstatine derivative (orlistat). An analysis of all clinical trials - over ten-week long - is also presented for medications used in the management of obesity, as well as data about future medications, such as a the inverse cannabinoid agonist, rimonabant.

scholarly journals Hepatic Mitogen-Activated Protein Kinase Phosphatase 1 Selectively Regulates Glucose Metabolism and Energy Homeostasis

2014 ◽  
Vol 35 (1) ◽  
pp. 26-40 ◽  
Author(s):  
Ahmed Lawan ◽  
Lei Zhang ◽  
Florian Gatzke ◽  
Kisuk Min ◽  
Michael J. Jurczak ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Glucose Metabolism ◽  
Energy Homeostasis ◽  
Mitogen Activated Protein Kinase ◽  
Hepatic Insulin Resistance ◽  
Fibroblast Growth Factor 21 ◽  
High Fat ◽  
Mitogen Activated Protein ◽  
Fat Feeding

The liver plays a critical role in glucose metabolism and communicates with peripheral tissues to maintain energy homeostasis. Obesity and insulin resistance are highly associated with nonalcoholic fatty liver disease (NAFLD). However, the precise molecular details of NAFLD remain incomplete. The p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) regulate liver metabolism. However, the physiological contribution of MAPK phosphatase 1 (MKP-1) as a nuclear antagonist of both p38 MAPK and JNK in the liver is unknown. Here we show that hepatic MKP-1 becomes overexpressed following high-fat feeding. Liver-specific deletion of MKP-1 enhances gluconeogenesis and causes hepatic insulin resistance in chow-fed mice while selectively conferring protection from hepatosteatosis upon high-fat feeding. Further, hepatic MKP-1 regulates both interleukin-6 (IL-6) and fibroblast growth factor 21 (FGF21). Mice lacking hepatic MKP-1 exhibit reduced circulating IL-6 and FGF21 levels that were associated with impaired skeletal muscle mitochondrial oxidation and susceptibility to diet-induced obesity. Hence, hepatic MKP-1 serves as a selective regulator of MAPK-dependent signals that contributes to the maintenance of glucose homeostasis and peripheral tissue energy balance. These results also demonstrate that hepatic MKP-1 overexpression in obesity is causally linked to the promotion of hepatosteatosis.

scholarly journals Alterations of the triglyceride/fatty acid cycle contribute to the development of insulin resistance.

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Colleen Marie Croniger ◽  
Chang‐Wen Hsieh ◽  
David DeSantis ◽  
Aga Gornicka ◽  
Carrie Millward
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Acid Cycle ◽  
Triglyceride Fatty Acid

scholarly journals Developmental Exposure to Endocrine Disrupting Chemicals and Its Impact on Cardio-Metabolic-Renal Health

2021 ◽  
Vol 3 ◽  
Author(s):  
Radha Dutt Singh ◽  
Kavita Koshta ◽  
Ratnakar Tiwari ◽  
Hafizurrahman Khan ◽  
Vineeta Sharma ◽  
...  
Keyword(s):  
Experimental Evidence ◽  
Energy Homeostasis ◽  
Endocrine Disrupting Chemicals ◽  
Developmental Exposure ◽  
Adverse Health Outcomes ◽  
Early Life Exposure ◽  
Endocrine Disrupting ◽  
Similar Mode ◽  
Health And Disease ◽  
Hormone System

Developmental origin of health and disease postulates that the footprints of early life exposure are followed as an endowment of risk for adult diseases. Epidemiological and experimental evidence suggest that an adverse fetal environment can affect the health of offspring throughout their lifetime. Exposure to endocrine disrupting chemicals (EDCs) during fetal development can affect the hormone system homeostasis, resulting in a broad spectrum of adverse health outcomes. In the present review, we have described the effect of prenatal EDCs exposure on cardio-metabolic-renal health, using the available epidemiological and experimental evidence. We also discuss the potential mechanisms of their action, which include epigenetic changes, hormonal imprinting, loss of energy homeostasis, and metabolic perturbations. The effect of prenatal EDCs exposure on cardio-metabolic-renal health, which is a complex condition of an altered biological landscape, can be further examined in the case of other environmental stressors with a similar mode of action.

scholarly journals The Ins and Outs of Iron Homeostasis

Physiology ◽  
2006 ◽  
Vol 21 (2) ◽  
pp. 115-123 ◽  
Author(s):  
Adriana Donovan ◽  
Cindy N. Roy ◽  
Nancy C. Andrews
Keyword(s):  
Iron Transport ◽  
Iron Homeostasis ◽  
Essential Element ◽  
Regulatory Mechanisms ◽  
Health And Disease ◽  
And Storage ◽  
Different Tissues

Iron is an essential element that is toxic when it accumulates in excess. Intricate regulatory mechanisms have evolved to maintain iron homeostasis within cells and between different tissues of complex organisms. This review discusses the proteins involved in iron transport and storage and their regulation in health and disease.

The Salivary miRNome: A Promising Biomarker of Disease

MicroRNA ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sara Tomei ◽  
Harshitha Shobha Manjunath ◽  
Selvasankar Murugesan ◽  
Souhaila Al Khodor
Keyword(s):  
Current Knowledge ◽  
Transcriptional Level ◽  
Biological Processes ◽  
Circulating Mirnas ◽  
Disease Pathogenesis ◽  
Technical Aspects ◽  
Recent Developments ◽  
Health And Disease ◽  
Non Coding Rnas

: MicroRNAs (miRNAs) are non-coding RNAs ranging from 18-24 nucleotides also known to regulate the human genome mainly at the post-transcriptional level. MiRNAs were shown to play an important role in most biological processes such as apoptosis and in the pathogenesis of many diseases such as cardiovascular diseases and cancer. Recent developments of advanced molecular high-throughput technologies have enhanced our knowledge of miRNAs. MiRNAs can now be discovered, interrogated, and quantified in various body fluids, and hence can serve as diagnostic and therapeutic markers for many diseases. While most studies use blood as a sample source to measure circulating miRNAs as possible biomarkers for disease pathogenesis, fewer studies have assessed the role of salivary miRNAs in health and disease. This review aims at providing an overview of the current knowledge of the salivary miRNome, addressing the technical aspects of saliva sampling and highlighting the applicability of miRNA screening to clinical practice.

scholarly journals EVALUATION OF CYCLIC ADENOSINE MONOPHOSPHATE AND NEUROTRANSMITTERS IN EXPERIMENTAL OBESITY: IMPACT OF BLACK PEPPER AND COFFEE AQUEOUS EXTRACTS

2016 ◽  
Vol 9 (9) ◽  
pp. 87 ◽  
Author(s):  
Yasmin Abdel Latif ◽  
Shadia Fathy ◽  
Zakaria El-khayat ◽  
Maha Moustafa ◽  
Abdel Razik Farrag ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Lipid Profile ◽  
High Performance ◽  
Energy Homeostasis ◽  
Body Weight Gain ◽  
Serum Insulin ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Black Pepper

ABSTRACTObjective: This study aims to evaluate the effect of black pepper and coffee extracts on chronic and acute experimental-induced obesity and energyhomeostasis.Methods: Rats were divided into 10 groups including control, high-fat diet (HFD), triton, HFD+triton, black pepper+HFD, black pepper+HFD+triton,coffee+HFD, coffee+HFD+triton, mixture+HFD, and mixture+HFD+triton groups. Blood glucose, serum insulin, and insulin resistance were estimated.Body mass index, food efficiency intake, and body weight gain were calculated. Lipid profile, liver and kidney functions were measured, serum and braincyclic adenosine monophosphate (cAMP) was estimated, and brain neurotransmitters were measured by high-performance liquid chromatography.Furthermore, histopathology of liver was performed.Results: Findings showed that blood glucose, insulin resistance, lipid profile, kidney and liver functions as well as brain cAMP and neurotransmitterswere significantly increased, concomitant with a significant decrease in insulin resistance and serum cAMP in both HFD and triton-induced obesitygroups compared to control.Conclusion: Supplementation with black pepper extract, coffee extract, and a mixture of both significantly improved these findings. In conclusion,black pepper and coffee extracts are overlooked as promising weight reduction and antihyperlipidemic agents.Keywords: Energy homeostasis, Obesity, Black pepper extract, Coffee extract, Cyclic adenosine monophosphate, Neurotransmitters.

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