Short-Term Curcumin Gavage Sensitizes Insulin Signaling in Dexamethasone-Treated C57BL/6 Mice

Chronic consumption of high-fat-and-fructose diets (HFFD) is associated with the development of insulin resistance (InsRes) and obesity. Systemic insulin resistance resulting from long-term HFFD feeding has detrimental consequences on cognitive performance, neurogenesis, and long-term potentiation establishment, accompanied by neuronal alterations in the hippocampus. However, diet-induced hippocampal InsRes has not been reported. Therefore, we investigated whether short-term HFFD feeding produced hippocampal insulin signaling alterations associated with neuronal changes in the hippocampus. Rats were fed with a control diet or an HFFD consisting of 10% lard supplemented chow and 20% high-fructose syrup in the drinking water. Our results show that 7 days of HFFD feeding induce obesity and InsRes, associated with the following alterations in the hippocampus: (1) a decreased insulin signaling; (2) a decreased hippocampal weight; (3) a reduction in dendritic arborization in CA1 and microtubule-associated protein 2 (MAP-2) levels; (4) a decreased dendritic spine number in CA1 and synaptophysin content, along with an increase in tau phosphorylation; and finally, (5) an increase in reactive astrocyte associated with microglial changes. To our knowledge, this is the first report addressing hippocampal insulin signaling, as well as morphologic, structural, and functional modifications due to short-term HFFD feeding in the rat.

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Short-term physical inactivity induces diacylglycerol accumulation and insulin resistance in muscle via lipin1 activation

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00254.2020 ◽

2021 ◽

Author(s):

Saori Kakehi ◽

Yoshifumi Tamura ◽

Shin-ichi Ikeda ◽

Naoko Kaga ◽

Hikari Taka ◽

...

Keyword(s):

Insulin Sensitivity ◽

Signaling Pathway ◽

Insulin Signaling ◽

Physical Inactivity ◽

Insulin Signaling Pathway ◽

Dominant Negative ◽

Short Term ◽

Intramyocellular Lipids ◽

Cast Immobilization ◽

Impaired Insulin

Physical inactivity impairs muscle insulin sensitivity. However, its mechanism is unclear. To model physical inactivity, we applied 24-h hind-limb cast immobilization (HCI) to mice with normal or high fat diet (HFD), and evaluated intramyocellular lipids and the insulin signaling pathway in the soleus muscle. While 2-wk HFD alone did not alter intramyocellular diacylglycerol (IMDG) accumulation, HCI alone increased it by 1.9-fold and HCI after HFD further increased it by 3.3-fold. Parallel to this, we found increased PKCε activity, reduced insulin-induced 2-deoxy-glucose (2-DOG) uptake, and reduced phosphorylation of IRβ and Akt, key molecules for insulin signaling pathway. Lipin1, which converts phosphatidic acid to diacylglycerol, showed increase of its activity by HCI, and dominant-negative lipin1 expression in muscle prevented HCI-induced IMDG accumulation and impaired insulin-induced 2-DOG uptake. Further, 24-h leg cast immobilization in human increased lipin1 expression. Thus, even short-term immobilization increases IMDG and impairs insulin sensitivity in muscle via enhanced lipin1 activity.

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Src Family Kinase Links Insulin Signaling to Short Term Regulation of Na,K-ATPase in Nonpigmented Ciliary Epithelium

Journal of Cellular Physiology ◽

10.1002/jcp.25654 ◽

2016 ◽

Vol 232 (6) ◽

pp. 1489-1500 ◽

Cited By ~ 1

Author(s):

Mohammad Shahidullah ◽

Amritlal Mandal ◽

Nicholas A. Delamere

Keyword(s):

Insulin Signaling ◽

Ciliary Epithelium ◽

Src Family Kinase ◽

Short Term ◽

Nonpigmented Ciliary Epithelium

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Salicylate prevents hepatic insulin resistance caused by short-term elevation of free fatty acids in vivo

Journal of Endocrinology ◽

10.1677/joe-07-0005 ◽

2007 ◽

Vol 195 (2) ◽

pp. 323-331 ◽

Cited By ~ 56

Author(s):

Edward Park ◽

Victor Wong ◽

Xinyu Guan ◽

Andrei I Oprescu ◽

Adria Giacca

Keyword(s):

Insulin Resistance ◽

Insulin Signaling ◽

Glucose Utilization ◽

Serine Phosphorylation ◽

Hepatic Insulin Resistance ◽

Short Term ◽

Proinflammatory Mediators ◽

Phosphorylated Akt ◽

Stimulation Of

Recent evidence indicates that inflammatory pathways are causally involved in insulin resistance. In particular, Iκ Bα kinase β (IKKβ ), which can impair insulin signaling directly via serine phosphorylation of insulin receptor substrates (IRS) and/or indirectly via induction of transcription of proinflammatory mediators, has been implicated in free fatty acid (FFA)-induced insulin resistance in skeletal muscle. However, it is unclear whether liver IKKβ activation plays a causal role in hepatic insulin resistance caused by acutely elevated FFA. In the present study, we wished to test the hypothesis that sodium salicylate, which inhibits IKKβ , prevents hepatic insulin resistance caused by short-term elevation of FFA. To do this, overnight-fasted Wistar rats were subject to 7-h i.v. infusion of either saline or Intralipid plus 20 U/ml heparin (IH; triglyceride emulsion that elevates FFA levels in vivo) with or without salicylate. Hyperinsulinemic–euglycemic clamp with tracer infusion was performed to assess insulin-induced stimulation of peripheral glucose utilization and suppression of endogenous glucose production (EGP). Infusion of IH markedly decreased (P < 0.05) insulin-induced stimulation of peripheral glucose utilization and suppression of EGP, which were completely prevented by salicylate co-infusion. Furthermore, salicylate reversed IH-induced 1) decrease in Iκ Bα content; 2) increase in serine phosphorylation of IRS-1 (Ser 307) and IRS-2 (Ser 233); 3) decrease in tyrosine phosphorylation of IRS-1 and IRS-2; and 4) decrease in serine 473-phosphorylated Akt in the liver. These results demonstrate that inhibition of IKKβ prevents FFA-induced impairment of hepatic insulin signaling, thus implicating IKKβ as a causal mediator of hepatic insulin resistance caused by acutely elevated plasma FFA.

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Short Term Palmitate Supply Impairs Intestinal Insulin Signaling via Ceramide Production

Journal of Biological Chemistry ◽

10.1074/jbc.m115.709626 ◽

2016 ◽

Vol 291 (31) ◽

pp. 16328-16338 ◽

Cited By ~ 17

Author(s):

Thi Thu Trang Tran ◽

Bárbara Graziela Postal ◽

Sylvie Demignot ◽

Agnès Ribeiro ◽

Céline Osinski ◽

...

Keyword(s):

Insulin Signaling ◽

Short Term ◽

Ceramide Production

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Short-term heat stress altered metabolism and insulin signaling in skeletal muscle

Journal of Animal Science ◽

10.1093/jas/skx083 ◽

2018 ◽

Vol 96 (1) ◽

pp. 154-167 ◽

Cited By ~ 3

Author(s):

Shanthi Ganesan ◽

Corey M Summers ◽

Sarah C Pearce ◽

Nicholas K Gabler ◽

Rudy J Valentine ◽

...

Keyword(s):

Skeletal Muscle ◽

Heat Stress ◽

Insulin Signaling ◽

Short Term ◽

Altered Metabolism

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Cardioprotective effects of short-term empagliflozin treatment in db/db mice

Scientific Reports ◽

10.1038/s41598-020-76698-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Bernhard Radlinger ◽

Florian Hornsteiner ◽

Sabrina Folie ◽

Willi Salvenmoser ◽

Bernhard J. Haubner ◽

...

Keyword(s):

Body Weight ◽

Insulin Signaling ◽

Glucose Transporter ◽

Cardiac Tissue ◽

Citrate Synthase ◽

Treated Group ◽

Mitochondrial Morphology ◽

Short Term ◽

Cardiac Inflammation ◽

Cardioprotective Effects

AbstractSodium glucose transporter (SGLT)-2 inhibitors have consistently shown cardioprotective effects independent of the glycemic status of treated patients. In this study we aimed to investigate underlying mechanisms of short-term empagliflozin treatment in a mouse model of type II diabetes. Male db/db mice were fed a western type diet with or without enrichment with empagliflozin for 7 days. While glucose tolerance was significantly improved in empagliflozin treated mice, body weight and fasting insulin levels were comparable in both groups. Cardiac insulin signaling activity indicated by reduced proteinkinase B (AKT) phosphorylation was significantly decreased in the empagliflozin treated group. Remarkably, mitochondrial mass estimated by citrate synthase activity was significantly elevated in empagliflozin treated mice. Accordingly, mitochondrial morphology was significantly altered upon treatment with empagliflozin as analysed by transmission electron microscopy. Additionally, short-term empagliflozin therapy was associated with a changed cardiac tissue cytokine expression in favor of an anti-inflammatory pattern. Our data suggest that early cardioprotection in empagliflozin treated mice is independent of a reduction in body weight or hyperinsulinemia. Ameliorated mitochondrial ultrastructure, attenuated cardiac insulin signaling and diminished cardiac inflammation might contribute to the cardioprotective effects of empagliflozin.

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