scholarly journals Role of Nutrient and Energy Sensors in the Development of Type 2 Diabetes

2021 ◽  
Author(s):  
Verónica Hurtado-Carneiro ◽  
Ana Pérez-García ◽  
Elvira Álvarez ◽  
Carmen Sanz
Keyword(s):  
Type 2 Diabetes ◽  
Nutrient Availability ◽  
Energy Demand ◽  
Metabolic Response ◽  
Whole Body ◽  
Key Factor ◽  
Control Food ◽  
Control Food Intake

Cell survival depends on the constant challenge to match energy demands with nutrient availability. This process is mediated through a highly conserved network of metabolic fuel sensors that orchestrate both a cellular and whole-body energy balance. A mismatch between cellular energy demand and nutrient availability is a key factor in the development of type 2 diabetes, obesity, metabolic syndrome, and other associated pathologies; thus, understanding the fundamental mechanisms by which cells detect nutrient availability and energy demand may lead to the development of new treatments. This chapter reviews the role of the sensor PASK (protein kinase with PAS domain), analyzing its role in the mechanisms of adaptation to nutrient availability and the metabolic response in different organs (liver, hypothalamus) actively cooperating to control food intake, maintain glycaemia homeostasis, and prevent insulin resistance and weight gain.

scholarly journals Physical Exercise as Therapy for Type 2 Diabetes Mellitus: From Mechanism to Orientation

2019 ◽  
Vol 74 (4) ◽  
pp. 313-321 ◽  
Author(s):  
Dan Yang ◽  
Yifan Yang ◽  
Yanlin Li ◽  
Rui Han
Keyword(s):  
Type 2 Diabetes ◽  
Exercise Therapy ◽  
Metabolic Diseases ◽  
Whole Body ◽  
Mechanism Study ◽  
Physiological Mechanisms ◽  
Glycolipid Metabolism ◽  
Randomized Controlled Studies

Background: Exercise therapy plays an important role in the prevention and treatment of type 2 diabetes (T2DM). The mechanism of exercise therapy in the improvement of glycolipid metabolism of T2DM is very complex and not completely clear. Summary: Exercise training improves the whole body metabolic health in patients with T2DM, leading to an increase in glycolipid uptake and utilization, improved insulin sensitivity, optimized body mass index, and modulated DNA methylation, etc. Recent findings support that some cytokines such as irisin, osteocalcin, and adiponectin are closely related to exercise and metabolic diseases. This study briefly reviews the physiological mechanisms of exercise therapy in diabetes and the potential role of these cytokines in exercise. Key Messages: More high-quality, targeted, randomized controlled studies are needed urgently, from mechanism study to treatment direction, to provide a more theoretical basis for exercise therapy and to explore new therapeutic targets for diabetes.

scholarly journals Lkb1 suppresses amino acid-driven gluconeogenesis in the liver

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Pierre-Alexandre Just ◽  
Sara Charawi ◽  
Raphaël G. P. Denis ◽  
Mathilde Savall ◽  
Massiré Traore ◽  
...  
Keyword(s):  
Amino Acid ◽  
Glucose Production ◽  
Whole Body ◽  
Postprandial Period ◽  
Key Factor ◽  
Liver Kinase B1 ◽  
Whole Body Metabolism ◽  
Specific Deletion

AbstractExcessive glucose production by the liver is a key factor in the hyperglycemia observed in type 2 diabetes mellitus (T2DM). Here, we highlight a novel role of liver kinase B1 (Lkb1) in this regulation. We show that mice with a hepatocyte-specific deletion of Lkb1 have higher levels of hepatic amino acid catabolism, driving gluconeogenesis. This effect is observed during both fasting and the postprandial period, identifying Lkb1 as a critical suppressor of postprandial hepatic gluconeogenesis. Hepatic Lkb1 deletion is associated with major changes in whole-body metabolism, leading to a lower lean body mass and, in the longer term, sarcopenia and cachexia, as a consequence of the diversion of amino acids to liver metabolism at the expense of muscle. Using genetic, proteomic and pharmacological approaches, we identify the aminotransferases and specifically Agxt as effectors of the suppressor function of Lkb1 in amino acid-driven gluconeogenesis.

scholarly journals The role of adipokines in β-cell failure of type 2 diabetes

2012 ◽  
Vol 216 (1) ◽  
pp. T37-T45 ◽  
Author(s):  
Simon J Dunmore ◽  
James E P Brown
Keyword(s):  
Type 2 Diabetes ◽  
Β Cells ◽  
Β Cell ◽  
Beneficial Effects ◽  
Published Evidence ◽  
Key Factor ◽  
Excessive Adiposity ◽  
Factor Α

β-Cell failure coupled with insulin resistance is a key factor in the development of type 2 diabetes. Changes in circulating levels of adipokines, factors released from adipose tissue, form a significant link between excessive adiposity in obesity and both aforementioned factors. In this review, we consider the published evidence for the role of individual adipokines on the function, proliferation, death and failure of β-cells, focusing on those reported to have the most significant effects (leptin, adiponectin, tumour necrosis factor α, resistin, visfatin, dipeptidyl peptidase IV and apelin). It is apparent that some adipokines have beneficial effects whereas others have detrimental properties; the overall contribution to β-cell failure of changed concentrations of adipokines in the blood of obese pre-diabetic subjects will be highly dependent on the balance between these effects and the interactions between the adipokines, which act on the β-cell via a number of intersecting intracellular signalling pathways. We emphasise the importance, and comparative dearth, of studies into the combined effects of adipokines on β-cells.

AMPK in Health and Disease

2009 ◽  
Vol 89 (3) ◽  
pp. 1025-1078 ◽  
Author(s):  
Gregory R. Steinberg ◽  
Bruce E. Kemp
Keyword(s):  
Energy Balance ◽  
Stress Responses ◽  
Energy Demand ◽  
Dynamic Control ◽  
Cellular Level ◽  
Whole Body ◽  
Α Subunit ◽  
Ampk Signaling ◽  
Control Food Intake

The function and survival of all organisms is dependent on the dynamic control of energy metabolism, when energy demand is matched to energy supply. The AMP-activated protein kinase (AMPK) αβγ heterotrimer has emerged as an important integrator of signals that control energy balance through the regulation of multiple biochemical pathways in all eukaryotes. In this review, we begin with the discovery of the AMPK family and discuss the recent structural studies that have revealed the molecular basis for AMP binding to the enzyme's γ subunit. AMPK's regulation involves autoinhibitory features and phosphorylation of both the catalytic α subunit and the β-targeting subunit. We review the role of AMPK at the cellular level through examination of its many substrates and discuss how it controls cellular energy balance. We look at how AMPK integrates stress responses such as exercise as well as nutrient and hormonal signals to control food intake, energy expenditure, and substrate utilization at the whole body level. Lastly, we review the possible role of AMPK in multiple common diseases and the role of the new age of drugs targeting AMPK signaling.

scholarly journals Interleukin-6 Expression by Hypothalamic Microglia in Multiple Inflammatory Contexts: A Systematic Review

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Vanessa C. D. Bobbo ◽  
Carlos P. Jara ◽  
Natália F. Mendes ◽  
Joseane Morari ◽  
Lício A. Velloso ◽  
...  
Keyword(s):  
Systematic Review ◽  
Interleukin 6 ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Whole Body ◽  
Positive Energy ◽  
Anatomical Site ◽  
Control Food ◽  
Control Food Intake

Interleukin-6 (IL-6) is a unique cytokine that can play both pro- and anti-inflammatory roles depending on the anatomical site and conditions under which it has been induced. Specific neurons of the hypothalamus provide important signals to control food intake and energy expenditure. In individuals with obesity, a microglia-dependent inflammatory response damages the neural circuits responsible for maintaining whole-body energy homeostasis, resulting in a positive energy balance. However, little is known about the role of IL-6 in the regulation of hypothalamic microglia. In this systematic review, we asked what types of conditions and stimuli could modulate microglial IL-6 expression in murine model. We searched the PubMed and Web of Science databases and analyzed 13 articles that evaluated diverse contexts and study models focused on IL-6 expression and microglia activation, including the effects of stress, hypoxia, infection, neonatal overfeeding and nicotine exposure, lipopolysaccharide stimulus, hormones, exercise protocols, and aging. The results presented in this review emphasized the role of “injury-like” stimuli, under which IL-6 acts as a proinflammatory cytokine, concomitant with marked microglial activation, which drive hypothalamic neuroinflammation. Emerging evidence indicates an important correlation of basal IL-6 levels and microglial function with the maintenance of hypothalamic homeostasis. Advances in our understanding of these different contexts will lead to the development of more specific pharmacological approaches for the management of acute and chronic conditions, like obesity and metabolic diseases, without disturbing the homeostatic functions of IL-6 and microglia in the hypothalamus.

The role of oncostatin m in the development of type 2 diabetes associated with obesity

2018 ◽  
Author(s):  
Siri Taxeras ◽  
Irene Piquer-Garcia ◽  
Silvia Pellitero ◽  
Rocio Puig ◽  
Eva Martinez ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Oncostatin M
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