scholarly journals The Endogenous Cannabinoid System Stimulates Glucose Uptake in Human Fat Cells via Phosphatidylinositol 3-Kinase and Calcium-Dependent Mechanisms

2007 ◽  
Vol 92 (12) ◽  
pp. 4810-4819 ◽  
Author(s):  
Claudio Pagano ◽  
Catia Pilon ◽  
Alessandra Calcagno ◽  
Riccardo Urbanet ◽  
Marco Rossato ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Uptake ◽  
Cannabinoid Receptors ◽  
Glucose Transporter ◽  
Peroxisome Proliferator ◽  
Fat Cells ◽  
Human Adipocytes ◽  
Cannabinoid System ◽  
Endogenous Cannabinoid ◽  
Endogenous Cannabinoid System

Abstract Background: The endogenous cannabinoid system participates in the regulation of energy balance, and its dysregulation may be implicated in the pathogenesis of obesity. Adipose tissue endocannabinoids may produce metabolic and endocrine effects, but very few data are available in human adipose tissue and in primary human fat cells. Experimental Design: We measured expression of type 1 and type 2 cannabinoid receptors (CNR), enzymes of cannabinoids synthesis and degradation in human omental, sc abdominal, and gluteal adipose tissue from lean and obese subjects. Furthermore, we assessed the effect of CNR1 stimulation on glucose uptake and intracellular transduction mechanisms in primary human adipocytes. Then we assessed the reciprocal regulation between CNR1 and peroxisome proliferator-activated receptor-γ (PPARγ). Finally, we tested whether leptin and adiponectin are regulated by CNR1 in human adipocytes. Results: We found that most genes of the endocannabinoid system are down-regulated in gluteal fat and up-regulated in visceral and sc abdominal adipose tissue of obese patients. Treatment of adipocytes with rosiglitazone markedly down-regulated CNR1 expression, whereas Win 55,212 up-regulated PPARγ. Win 55,212 increased (+50%) glucose uptake, the translocation of glucose transporter 4, and intracellular calcium in fat cells. All these effects were inhibited by SR141716 and wortmannin and by removing extracellular calcium. Win 55,212 and SR141716 had no effect on expression of adiponectin and leptin. Conclusions: These results indicate a role for the local endocannabinoids in the regulation of glucose metabolism in human adipocytes and suggest a role in channeling excess energy fuels to adipose tissue in obese humans.

scholarly journals PPARγ-Independent Increase in Glucose Uptake and Adiponectin Abundance in Fat Cells

Endocrinology ◽  
2011 ◽  
Vol 152 (10) ◽  
pp. 3648-3660 ◽  
Author(s):  
Olga Dubuisson ◽  
Emily J. Dhurandhar ◽  
Rashmi Krishnapuram ◽  
Heather Kirk-Ballard ◽  
Alok K. Gupta ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glycemic Control ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Human Adipose Tissue ◽  
Peroxisome Proliferator ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Glucose Transporter 1

Although thiazolidinediones (TZD) effectively improve hyperglycemia and increase adiponectin, a proinsulin-sensitizing adipokine, they also increase adipogenesis via peroxisome proliferator-activated receptor (PPAR)γ induction, which may be undesirable. Recent safety concerns about some TZD have prompted the search for next generation agents that can enhance glycemic control and adiponectin independent of PPARγ or adipogenesis. Reminiscent of TZD action, a human adenovirus, adenovirus 36 (Ad36), up-regulates PPARγ, induces adipogenesis, and improves systemic glycemic control in vivo. We determined whether this effect of Ad36 requires PPARγ and/or adipogenesis. Glucose uptake and relevant cell signaling were determined in mock-infected or human adenoviruses Ad36 or Ad2-infected cell types under the following conditions: 1) undifferentiated human-adipose-tissue-derived stem cells (hASC), 2) hASC differentiated as adipocytes, 3) hASC in presence or absence of a PPARγ inhibitor, 4) NIH/3T3 that have impaired PPARγ expression, and 5) PPARγ-knockout mouse embryonic fibroblasts. Mouse embryonic fibroblasts with intact PPARγ served as a positive control. Additionally, to determine natural Ad36 infection, human sera were screened for Ad36 antibodies. In undifferentiated or differentiated hASC, or despite the inhibition, down-regulation, or the absence of PPARγ, Ad36 significantly enhanced glucose uptake and PPARγ, adiponectin, glucose transporter 4, and glucose transporter 1 protein abundance, compared with mock or Ad2-infected cells. This indicated that Ad36 up-regulates glucose uptake and adiponectin secretion independent of adipogenesis or without recruiting PPARγ. In humans, natural Ad36 infection predicted greater adiponectin levels, suggesting a human relevance of these effects. In conclusion, Ad36 provides a novel template to metabolically remodel human adipose tissue to enhance glycemic control without the concomitant increase in adiposity or PPARγ induction associated with TZD actions.

ACTIVATION OF THE ENDOGENOUS CANNABINOID SYSTEM STIMULATES ADIPOGENESIS IN HUMAN ADIPOSE TISSUE

2008 ◽  
Vol 19 ◽  
pp. S45
Author(s):  
Vettor Roberto ◽  
Pagano Claudio ◽  
Pilon Catia ◽  
Calcagno Alessandra ◽  
Urbanet Riccardo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Cannabinoid System ◽  
Endogenous Cannabinoid ◽  
Endogenous Cannabinoid System

scholarly journals Methylamine Activates Glucose Uptake in Human Adipocytes Without Overpassing Action of Insulin or Stimulating its Secretion in Pancreatic Islets

Medicines ◽  
2019 ◽  
Vol 6 (3) ◽  
pp. 89 ◽  
Author(s):  
Carpéné ◽  
Mauriège ◽  
Boulet ◽  
Biron ◽  
Grolleau ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Uptake ◽  
Pancreatic Islets ◽  
Amine Oxidase ◽  
Fat Cells ◽  
Obese Women ◽  
Human Adipocytes ◽  
Isolated Pancreatic Islets ◽  
Insulin Responsiveness

Background: Methylamine, a natural soluble amine present in foods, is known to be a substrate of primary amine oxidase (PrAO) widely expressed in animal tissues. Methylamine has been reported to activate glucose transport in fat cells and to facilitate glucose disposal in rabbits but the interests and limits of such insulin-mimicking actions have not been further explored. This work aimed to perform a preclinical study of the inter-individual variations of these biological properties to study the putative link between PrAO activity and insulin resistance. Methods: Methylamine was tested on human adipocyte preparations and in rabbit pancreatic islets to determine its influence on glucose uptake and insulin release, respectively. PrAO activity and related responses were determined in adipose tissues obtained from two cohorts of non-obese and obese women. Results: Adipose tissue PrAO activity was negatively correlated with insulin resistance in high-risk obese women. PrAO-dependent activation of glucose uptake was negatively correlated with body mass index and reflected the decrease of insulin responsiveness of human fat cells with increasing obesity. Methylamine exhibited antilipolytic properties in adipocytes but was unable to directly activate insulin secretion in isolated pancreatic islets. Conclusions: PrAO activation by its substrates, e.g., methylamine, increases glucose utilization in human adipocytes in a manner that is linked to insulin responsiveness. Methylamine/PrAO interaction can therefore contribute to adipose tissue enlargement but should be considered as potentially useful for diabetes prevention since it could limit lipotoxicity and facilitate glucose handling, at the expense of favoring healthy fat accumulation.

scholarly journals Antihyperglycemic and Antilipidemic Effects of the Ethanol Extract Mixture of Ligularia fischeri and Momordica charantia in Type II Diabetes-Mimicking Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-15
Author(s):  
Hyun Jin Baek ◽  
Yong Joon Jeong ◽  
Jeong Eun Kwon ◽  
Jong Sung Ra ◽  
Sung Ryul Lee ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Uptake Rate ◽  
Glucose Transporter ◽  
Synergistic Effects ◽  
Momordica Charantia ◽  
C2c12 Cells ◽  
Peroxisome Proliferator ◽  
Glucose Uptake Rate ◽  
Ligularia Fischeri

The extract of the Momordica charantia fruit (MCE) is recognized as an alternative treatment for diabetes. The extract of Ligularia fischeri leaves (LFE) is traditionally used as a folk medicine for treating inflammatory diseases in Korea as well. In this study, we investigated the synergistic effect of MCE combined with LFE on antihyperglycemic and antihyperlipidemic potentials. Based on the α-glucosidase inhibitory effect and promotion of adipocyte differentiation in the 3T3-L1 cell line, the MLM was prepared with MCE:LFE (8:2 weight:weight). MLM showed the synergistic effects in the promotion of the glucose uptake rate, suppression of dipeptidyl peptidase-4 (DPP-4) mRNA expression, upregulation of an insulin receptor substrate and glucose transporter type-4 expression, and an increase in insulin-associated signaling in C2C12 cells. In addition, the efficacy of peroxisome proliferator-activated receptor-γ agonism and glucose uptake rate by MLM supplementation was significantly enhanced in vitro. Then, the antihyperglycemic and antihyperlipidemic effects of MCE, LFE, and MLM at the dose of 50, 100, and 200 mg/kg/day (n = 6 per each group) were determined in streptozotocin (STZ)-insulted mice fed an atherogenic diet (ATH) for 4 weeks. In addition, MLM (50, 100, and 200 mg/kg/day, n = 5 per each group) was supplemented in ATH-fed db/db mice for 10 weeks. Compared with MCE or LFE alone, MLM supplementation led to a more significant reduction of glucose levels in both STZ/ATH and db/db/ATH mice as well as lowered lipid profiles in STZ/ATH mice. In addition, the stimulation of islet of Langerhans regeneration was more pronounced by MLM supplementation in both mice models. In conclusion, antihyperglycemic and antihyperlipidemic effects were strengthened by the combined extracts of L. fischeri and M. charantia (MLM) in diabetes-mimicking mice.

scholarly journals The Orexigenic Effect of Ghrelin Is Mediated through Central Activation of the Endogenous Cannabinoid System

PLoS ONE ◽  
2008 ◽  
Vol 3 (3) ◽  
pp. e1797 ◽  
Author(s):  
Blerina Kola ◽  
Imre Farkas ◽  
Mirjam Christ-Crain ◽  
Gábor Wittmann ◽  
Francesca Lolli ◽  
...  
Keyword(s):  
Central Activation ◽  
Cannabinoid System ◽  
Endogenous Cannabinoid ◽  
Endogenous Cannabinoid System

The endogenous cannabinoid system controls extinction of aversive memories

Nature ◽  
2002 ◽  
Vol 418 (6897) ◽  
pp. 530-534 ◽  
Author(s):  
Giovanni Marsicano ◽  
Carsten T. Wotjak ◽  
Shahnaz C. Azad ◽  
Tiziana Bisogno ◽  
Gerhard Rammes ◽  
...  
Keyword(s):  
Cannabinoid System ◽  
Endogenous Cannabinoid ◽  
Endogenous Cannabinoid System

Control by the endogenous cannabinoid system of ras oncogene‐dependent tumor growth

2001 ◽  
Vol 15 (14) ◽  
pp. 1-17 ◽  
Author(s):  
Maurizio Bifulco ◽  
Chiara Laezza ◽  
Giuseppe Portella ◽  
Mario Vitale ◽  
Pierangelo Orlando ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Ras Oncogene ◽  
Cannabinoid System ◽  
Endogenous Cannabinoid ◽  
Endogenous Cannabinoid System

scholarly journals Alleviative Effect of Ruellia tuberosa L. on Insulin Resistance and Abnormal Lipid Accumulation in TNF-α-Treated FL83B Mouse Hepatocytes

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Hong-Jie Chen ◽  
Chih-Yuan Ko ◽  
Jian-Hua Xu ◽  
Yu-Chu Huang ◽  
James Swi-Bea Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Ethyl Acetate ◽  
Glucose Uptake ◽  
Insulin Signaling ◽  
Lipid Accumulation ◽  
Glucose Transporter ◽  
Peroxisome Proliferator ◽  
Glucose Transporter 2 ◽  
Tnf Α ◽  
Mouse Hepatocytes

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease, and most patients with T2DM develop nonalcoholic fatty liver disease (NAFLD). Both diseases are closely linked to insulin resistance (IR). Our previous studies demonstrated that Ruellia tuberosa L. (RTL) extract significantly enhanced glucose uptake in the skeletal muscles and ameliorated hyperglycemia and IR in T2DM rats. We proposed that RTL might be via enhancing hepatic antioxidant capacity. However, the potent RTL bioactivity remains unidentified. In this study, we investigated the effects of RTL on glucose uptake, IR, and lipid accumulation in vitro to mimic the T2DM accompanied by the NAFLD paradigm. FL83B mouse hepatocytes were treated with tumor necrosis factor-α (TNF-α) to induce IR, coincubated with oleic acid (OA) to induce lipid accumulation, and then, treated with RTL fractions, fractionated with n-hexane or ethyl acetate (EA), from column chromatography, and analyzed by thin-layer chromatography. Our results showed that the ethyl acetate fraction (EAf2) from RTL significantly increased glucose uptake and suppressed lipid accumulation in TNF-α plus OA-treated FL83B cells. Western blot analysis showed that EAf2 from RTL ameliorated IR by upregulating the expression of insulin-signaling-related proteins, including protein kinase B, glucose transporter-2, and peroxisome proliferator-activated receptor alpha in TNF-α plus OA-treated FL83B cells. The results of this study suggest that EAf2 from RTL may improve hepatic glucose uptake and alleviate lipid accumulation by ameliorating and suppressing the hepatic insulin signaling and lipogenesis pathways, respectively, in hepatocytes.

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