Acute Metabolic Effects of Exercise on Glucose Fluxes in Splanchnic and Peripheral Tissues in Diabetics, Determined with an Innovative Approach

2015 ◽  
pp. 216-226
Author(s):  
Ryuzo Kawamori ◽  
Minoru Kubota ◽  
Masahiko Ikeda ◽  
Munehide Matsuhisa ◽  
Masashi Kubota ◽  
...  
Keyword(s):  
Innovative Approach ◽  
Metabolic Effects ◽  
Peripheral Tissues

scholarly journals Kupffer cells facilitate the acute effects of leptin on hepatic lipid metabolism

2017 ◽  
Vol 312 (1) ◽  
pp. E11-E18 ◽  
Author(s):  
Anantha Metlakunta ◽  
Wan Huang ◽  
Maja Stefanovic-Racic ◽  
Nikolaos Dedousis ◽  
Ian Sipula ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Kupffer Cells ◽  
Liver Lipid ◽  
Myeloid Cell ◽  
Metabolic Effects ◽  
Acid Oxidation ◽  
Acute Effects ◽  
Peripheral Tissues ◽  
Liver Lipid Metabolism

Leptin has potent effects on lipid metabolism in a number of peripheral tissues. In liver, an acute leptin infusion (~120 min) stimulates hepatic fatty acid oxidation (~30%) and reduces triglycerides (TG, ~40%), effects that are dependent on phosphoinositol-3-kinase (PI3K) activity. In the current study we addressed the hypothesis that leptin actions on liver-resident immune cells are required for these metabolic effects. Myeloid cell-specific deletion of the leptin receptor (ObR) in mice or depletion of liver Kupffer cells (KC) in rats in vivo prevented the acute effects of leptin on liver lipid metabolism, while the metabolic effects of leptin were maintained in mice lacking ObR in hepatocytes. Notably, liver TG were elevated in both lean and obese myeloid cell ObR, but the degree of obesity and insulin resistance induced by a high-fat diet was similar to control mice. In isolated primary hepatocytes (HEP), leptin had no effects on HEP lipid metabolism and only weakly stimulated PI3K. However, the coculture of KC with HEP restored leptin action on HEP fatty acid metabolism and stimulation of HEP PI3K. Notably, leptin stimulated the release from KC of a number of cytokines. However, the exposure of HEP to these cytokines individually [granulocyte macrophage colony-stimulating factor, IL-1α, IL-1β, IL-6, IL-10, and IL-18] or in combination had no effects on HEP lipid metabolism. Together, these data demonstrate a role for liver mononuclear cells in the regulation of liver lipid metabolism by leptin.

First-pass hepatic extraction and metabolic effects of insulin and insulin analogues

1987 ◽  
Vol 252 (2) ◽  
pp. E209-E217 ◽  
Author(s):  
Z. Chap ◽  
T. Ishida ◽  
J. Chou ◽  
C. J. Hartley ◽  
M. L. Entman ◽  
...  
Keyword(s):  
Glucose Utilization ◽  
Glucose Production ◽  
Insulin Analogues ◽  
Metabolic Effects ◽  
Combined Effects ◽  
Hepatic Extraction ◽  
Peripheral Tissues ◽  
First Pass ◽  
Biological Potency ◽  
Portal Infusion

First-pass hepatic extraction of insulin and hepatic and peripheral contributions to hypoglycemia were compared in conscious dogs during portal infusion of insulin A1, B29 diacetyl insulin, or A1-B29 dodecoyl insulin at 7 and 14 pmol X kg-1 X min-1. The liver removed 43 +/- 2% of insulin, 12 +/- 1% of dodecoyl, and 8 +/- 1% of diacetyl insulin, in a single transhepatic circulation. The hypoglycemia induced by insulin and diacetyl insulin and the ensuing glucagon response were greater than that produced by the dodecoyl analogue. Diacetyl insulin primarily increased glucose utilization, dodecoyl insulin solely inhibited hepatic production, and insulin affected both. The lack of hepatic effect of diacetyl insulin during hypoglycemia can be ascribed to greater counterregulation, because under euglycemic clamp conditions, this analogue caused suppression of glucose production. The different patterns of hypoglycemia exhibited can be explained by the combined effects of altered distribution between the liver and peripheral tissues caused by differences in hepatic extraction, the effect of this phenomenon on the counterregulatory response, and the intrinsic biological potency of the analogues.

scholarly journals Insulin and Insulin Resistance in Alzheimer’s Disease

2021 ◽  
Vol 22 (18) ◽  
pp. 9987
Author(s):  
Aleksandra Sędzikowska ◽  
Leszek Szablewski
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Cell Growth ◽  
Glucose Metabolism ◽  
Insulin Signaling ◽  
Brain Aging ◽  
Mapk Pathway ◽  
Metabolic Effects ◽  
Peripheral Tissues

Insulin plays a range of roles as an anabolic hormone in peripheral tissues. It regulates glucose metabolism, stimulates glucose transport into cells and suppresses hepatic glucose production. Insulin influences cell growth, differentiation and protein synthesis, and inhibits catabolic processes such as glycolysis, lipolysis and proteolysis. Insulin and insulin-like growth factor-1 receptors are expressed on all cell types in the central nervous system. Widespread distribution in the brain confirms that insulin signaling plays important and diverse roles in this organ. Insulin is known to regulate glucose metabolism, support cognition, enhance the outgrowth of neurons, modulate the release and uptake of catecholamine, and regulate the expression and localization of gamma-aminobutyric acid (GABA). Insulin is also able to freely cross the blood–brain barrier from the circulation. In addition, changes in insulin signaling, caused inter alia insulin resistance, may accelerate brain aging, and affect plasticity and possibly neurodegeneration. There are two significant insulin signal transduction pathways: the PBK/AKT pathway which is responsible for metabolic effects, and the MAPK pathway which influences cell growth, survival and gene expression. The aim of this study is to describe the role played by insulin in the CNS, in both healthy people and those with pathologies such as insulin resistance and Alzheimer’s disease.

scholarly journals Metabolic Systemic Effects Triiodothyronine

2020 ◽  
Vol 10 (4) ◽  
pp. 262-271
Author(s):  
E. A. Troshina ◽  
E. S. Senyushkina
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Depressive Disorders ◽  
Vital Role ◽  
The Body ◽  
Metabolic Effects ◽  
Metabolic Efficiency ◽  
Peripheral Tissues ◽  
Activation Of Transcription ◽  
Genes Encoding

Triiodothyronine (T3, 3,5,3’-L-triiodothyronine) is a thyroid hormone (thyroid), the secretion of which is carried out directly both by the gland (to a lesser extent) and outside it (the main amount; as a result of peripheral deiodination of thyroxine (T4)). Getting into the nuclei of cells, T3 interacts with specific nuclear receptors of target tissues, which determines its biological activity. This interaction leads to the activation of transcription of a number of genes.In the pituitary gland and peripheral tissues, the action of thyroid hormones is modulated by local deiodinases, which convert T4 to more active T3, the molecular effects of which in individual tissues depend on subtypes of T3 receptors and their interaction with other ligands, coactivators and corepressors, as well as on the activation or repression of specific genes.The reason for the lack of T3 production is primarily a deficiency of iodine in the diet, less often, a defect in the genes encoding the proteins that are involved in T3 biosynthesis. As a result of the low intake of iodide in the body, the so-called adaptive mechanism is activated, which consists in increasing the proportion of synthesized T3, which increases the metabolic efficiency of thyroid homones. With a deficiency in the diet of such a trace element as selenium, the conversion of T4 to T3 is reduced.Thyroid hormones play a vital role in the regulation of homeostasis and the metabolic rate of cells and tissues of humans and mammals. They are necessary for physical and mental development. Their insufficient production at the stage of formation of the internal organs of the fetus and in childhood can lead to various pathologies, primarily to pathology of the central nervous system, and as a result, growth retardation and mental retardation. In adulthood, hypothyroidism leads to a decrease in metabolism, memory impairment, depressive disorders, impaired fertility. Many discussions and ambiguous conclusions have been obtained regarding combination drugs (sodium levothyroxine + lyothironon) for the treatment of hypothyroidism. This article will examine the metabolic effects of T3, the thyroid hormone with the highest activity. 

CB1Rs in VMH Neurons Regulate Glucose Homeostasis but not Body Weight

2021 ◽  
Author(s):  
Carlos M Castorena ◽  
Alexandre Caron ◽  
Natalie J Michael ◽  
Newaz I Ahmed ◽  
Amanda G Arnold ◽  
...  
Keyword(s):  
Body Weight ◽  
Side Effects ◽  
Glucose Homeostasis ◽  
Ventromedial Hypothalamus ◽  
Metabolic Effects ◽  
Peripheral Tissues ◽  
Inverse Agonists ◽  
Affect Body Weight ◽  
The Central Nervous System ◽  
Key Sites

Cannabinoid 1 receptor (CB1R) inverse-agonists reduce body weight and improve several parameters of glucose homeostasis. However, these drugs have also been associated with deleterious side effects. CB1R expression is widespread in the brain and in peripheral tissues, but whether specific sites of expression can mediate the beneficial metabolic effects of CB1R drugs, while avoiding the untoward side effects, remains unclear. Evidence suggests inverse-agonists may act on key sites within the central nervous system to improve metabolism. The ventromedial hypothalamus (VMH) is a critical node regulating energy balance and glucose homeostasis. To determine the contributions of CB1Rs expressed in VMH neurons in regulating metabolic homeostasis, we generated mice lacking CB1Rs in the VMH. We found that deletion of CB1Rs in the VMH did not affect body weight in male and female mice fed chow or HFD. We also found that deletion of CB1Rs in the VMH did not alter weight loss responses induced by the CB1R inverse-agonists SR141716. However, we did find that CB1Rs of the VMH regulate parameters of glucose homeostasis independent of body weight in diet-induced obese male mice.

Gastric inhibitory polypeptide: a gut hormone with anabolic functions

1989 ◽  
Vol 2 (3) ◽  
pp. 169-174 ◽  
Author(s):  
B. Beck
Keyword(s):  
Adipose Tissue ◽  
Intestinal Secretion ◽  
Gastric Inhibitory Polypeptide ◽  
Metabolic Effects ◽  
Gastrointestinal Hormone ◽  
Peripheral Tissues ◽  
Gut Hormone ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
The Brain

Summary The gastrointestinal hormone, gastric inhibitory polypeptide (GIP), has been isolated and characterized because of its enterogastrone-type effects. It is also named glucose-dependent insulinotropic polypeptide and is actually considered to be the main incretin factor of the entero-insular axis. Besides these well-described effects on gastric secretion and pancreatic β cells, it also has direct metabolic effects on other tissues and organs, such as adipose tissue, liver, muscle, gastrointestinal tract and brain. In adipose tissue it is involved in the activation and regulation of lipoprotein lipase (LPL); it also inhibits glucagon-induced lipolysis and potentiates the effect of insulin on incorporation of fatty acids into triglycerides. It may play a role in the development of obesity because of the hypersensitivity of adipose tissue of obese animals to some of these actions. In the liver it does not modify insulin extraction, and its incretin effects are due only to the stimulation of insulin secretion and synthesis. It reduces hepatic glucose output and inhibits glucagon-stimulated glycogenolysis. It might increase glucose utilization in peripheral tissues such as muscle. GIP also has an effect on the volume and/or electrolyte composition of intestinal secretion and saliva. The functional importance of its effect on the hormones of the anterior pituitary lobe remains to be established, as it has never been detected in the brain. Its links with insulin are very close and the presence of insulin is sometimes necessary for the greater efficiency of both hormones. GIP can be considered as a true metabolic hormone, with most of its functions tending to increase anabolism.

scholarly journals GH signaling in human adipose and muscle tissue during ‘feast and famine’: amplification of exercise stimulation following fasting compared to glucose administration

2015 ◽  
Vol 173 (3) ◽  
pp. 283-290 ◽  
Author(s):  
Mikkel H Vendelbo ◽  
Britt Christensen ◽  
Solbritt B Grønbæk ◽  
Morten Høgild ◽  
Michael Madsen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Muscle Tissue ◽  
Target Gene ◽  
Exercise Bout ◽  
Metabolic Effects ◽  
Cytokine Signaling ◽  
Peripheral Tissues ◽  
Target Gene Expression ◽  
Gh Secretion

ObjectiveFasting and exercise stimulates, whereas glucose suppresses GH secretion, but it is uncertain how these conditions impact GH signaling in peripheral tissues. To test the original ‘feast and famine hypothesis’ by Rabinowitz and Zierler, according to which the metabolic effects of GH are predominant during fasting, we specifically hypothesized that fasting and exercise act in synergy to increase STAT-5b target gene expression.Design and methodsEight healthy men were studied on two occasions in relation to a 1 h exercise bout: i) with a concomitant i.v. glucose infusion (‘feast’) and ii) after a 36 h fast (‘famine’). Muscle and fat biopsy specimens were obtained before, immediately after, and 30 min after exercise.ResultsGH increased during exercise on both examination days and this effect was amplified by fasting, and free fatty acid (FFA) levels increased after fasting. STAT-5b phosphorylation increased similarly following exercise on both occasions. In adipose tissue, suppressors of cytokine signaling 1 (SOCS1) and SOCS2 were increased after exercise on the fasting day and both fasting and exercise increased cytokine inducible SH2-containing protein (CISH). In muscle, SOCS2 and CISH mRNA were persistently increased after fasting. Muscle SOCS1, SOCS3, and CISH mRNA expression increased, whereas SOCS2 decreased after exercise on both examination days.ConclusionsThis study demonstrates that fasting and exercise act in tandem to amplify STAT-5b target gene expression (SOCS and CISH) in adipose and muscle tissue in accordance with the ‘feast and famine hypothesis’; the adipose tissue signaling responses, which hitherto have not been scrutinized, may play a particular role in promoting FFA mobilization.

scholarly journals Endocannabinoids and Their Receptors as Targets for Obesity Therapy

Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2531-2536 ◽  
Author(s):  
Annette D. de Kloet ◽  
Stephen C. Woods
Keyword(s):  
Energy Homeostasis ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Metabolic Effects ◽  
Peripheral Tissues ◽  
Anabolic Action ◽  
Obesity Therapy ◽  
Glucose Profiles ◽  
Cb1 Antagonists

As the incidence of obesity continues to increase, the development of effective therapies is a high priority. The endocannabinoid system has emerged as an important influence on the regulation of energy homeostasis. The endocannabinoids anandamide and 2-arachidonoylglycerol act on cannabinoid receptor-1 (CB1) in the brain and many peripheral tissues causing a net anabolic action. This includes increasing food intake, and causing increased lipogenesis and fat storage in adipose tissue and liver. The endocannabinoid system is hyperactive in obese humans and animals, and treating them with CB1 antagonists causes weight loss and improved lipid and glucose profiles. Although clinical trials with CB1 antagonists have yielded beneficial metabolic effects, concerns about negative affect have limited the therapeutic potential of the first class of CB1 antagonists available.

Depot risperidone-induced adverse metabolic alterations in female rats

2017 ◽  
Vol 31 (4) ◽  
pp. 487-499 ◽  
Author(s):  
Katerina Horska ◽  
Jana Ruda-Kucerova ◽  
Michal Karpisek ◽  
Pavel Suchy ◽  
Radka Opatrilova ◽  
...  
Keyword(s):  
Weight Gain ◽  
Lipid Profile ◽  
Atypical Antipsychotics ◽  
Body Weight Gain ◽  
Female Rats ◽  
Metabolic Effects ◽  
Exposure Group ◽  
High Exposure ◽  
Peripheral Tissues ◽  
Metabolic Alterations

Atypical antipsychotics are associated with adverse metabolic effects including weight gain, increased adiposity, dyslipidaemia, alterations in glucose metabolism and insulin resistance. Increasing evidence suggests that metabolic dysregulation precedes weight gain development. The aim of this study was to evaluate alterations in adipokines, hormones and basic serum biochemical parameters induced by chronic treatment with depot risperidone at two doses (20 and 40 mg/kg) in female Sprague–Dawley rats. Dose-dependent metabolic alterations induced by risperidone after 6 weeks of treatment were revealed. Concomitant to weight gain and increased liver weight, an adverse lipid profile with an elevated triglyceride level was observed in the high exposure group, administered a 40 mg/kg dose repeatedly, while the low dose exposure group, administered a 20 mg/kg dose, developed weight gain without alterations in the lipid profile and adipokine levels. An initial peak in leptin serum level after the higher dose was observed in the absence of weight gain. This finding may indicate that the metabolic alterations observed in this study are not consequent to body weight gain. Taken together, these data may support the primary effects of atypical antipsychotics on peripheral tissues.

scholarly journals Neuronal Protein Tyrosine Phosphatase 1B Deficiency Results in Inhibition of Hypothalamic AMPK and Isoform-Specific Activation of AMPK in Peripheral Tissues

2009 ◽  
Vol 29 (16) ◽  
pp. 4563-4573 ◽  
Author(s):  
Bingzhong Xue ◽  
Thomas Pulinilkunnil ◽  
Incoronata Murano ◽  
Kendra K. Bence ◽  
Huamei He ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Target Genes ◽  
Fiber Type ◽  
Metabolic Effects ◽  
Whole Body ◽  
Acid Oxidation ◽  
Peripheral Tissues ◽  
Leptin Sensitivity ◽  
Brown Adipose ◽  
Ampk Activity

ABSTRACT PTP1B−/− mice are resistant to diet-induced obesity due to leptin hypersensitivity and consequent increased energy expenditure. We aimed to determine the cellular mechanisms underlying this metabolic state. AMPK is an important mediator of leptin's metabolic effects. We find that α1 and α2 AMPK activity are elevated and acetyl-coenzyme A carboxylase activity is decreased in the muscle and brown adipose tissue (BAT) of PTP1B−/− mice. The effects of PTP1B deficiency on α2, but not α1, AMPK activity in BAT and muscle are neuronally mediated, as they are present in neuron- but not muscle-specific PTP1B−/− mice. In addition, AMPK activity is decreased in the hypothalamic nuclei of neuronal and whole-body PTP1B−/− mice, accompanied by alterations in neuropeptide expression that are indicative of enhanced leptin sensitivity. Furthermore, AMPK target genes regulating mitochondrial biogenesis, fatty acid oxidation, and energy expenditure are induced with PTP1B inhibition, resulting in increased mitochondrial content in BAT and conversion to a more oxidative muscle fiber type. Thus, neuronal PTP1B inhibition results in decreased hypothalamic AMPK activity, isoform-specific AMPK activation in peripheral tissues, and downstream gene expression changes that promote leanness and increased energy expenditure. Therefore, the mechanism by which PTP1B regulates adiposity and leptin sensitivity likely involves the coordinated regulation of AMPK in hypothalamus and peripheral tissues.

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