scholarly journals Adipose tissue compensates for defect of phosphatidylinositol 3′-kinase induced in liver and muscle by dietary fish oil in fed rats

2006 ◽  
Vol 290 (1) ◽  
pp. E78-E86 ◽  
Author(s):  
Charlotte Corporeau ◽  
Christelle Le Foll ◽  
Mohammed Taouis ◽  
Jean-Paul Gouygou ◽  
Jean-Pascal Bergé ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fish Oil ◽  
Protein Content ◽  
Glucose Homeostasis ◽  
Insulin Signaling ◽  
Kinase Activity ◽  
Control Diet ◽  
Oral Glucose ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

The present work aimed to study in rats whether substitution of a low level of fish oil (FO; 2.2% of calories) into a low-fat diet (6.6% of calories from fat as peanut-rape oil or control diet) 1) has a tissue-specific effect on insulin signaling pathway and 2) prevents dexamethasone-induced alteration of insulin signaling in liver, muscle, and adipose tissue. Sixteen rats were used for study of insulin signaling, and sixteen rats received an oral glucose load (3 g/kg). Eight rats/group consumed control diet or diet containing FO over 5 wk. Four rats from each group received a daily intraperitoneal injection of saline or dexamethasone (1 mg·kg−1·day−1) for the last 5 days of feeding. In liver, FO decreased phosphatidylinositol 3′-kinase (PI 3′-kinase) activity by 54% compared with control diet. A similar result was obtained in muscle. In both liver and muscle, FO clearly amplified the effect of dexamethasone. FO did not alter early steps of insulin signaling, and in muscle GLUT4 protein content remained unaltered. In adipose tissue, FO increased PI 3′-kinase activity by 74%, whereas dexamethasone decreased it by 65%; inhibition of PI 3′-kinase activity by dexamethasone was similar in rats fed FO or control diet, and GLUT4 protein content was increased by 61% by FO. Glycemic and insulinemic responses to oral glucose were not modified by FO. In conclusion, FO increased PI 3′-kinase activity in adipose tissue while inhibiting it in liver and muscle. The maintenance of whole body glucose homeostasis suggests an important role of adipose tissue for control of glucose homeostasis.

Long-chain n-3 polyunsaturated fatty acids dissociate phosphorylation of Akt from phosphatidylinositol 3′-kinase activity in rats

2007 ◽  
Vol 292 (4) ◽  
pp. E1223-E1230 ◽  
Author(s):  
Christelle Le Foll ◽  
Charlotte Corporeau ◽  
Valérie Le Guen ◽  
Jean-Paul Gouygou ◽  
Jean-Pascal Bergé ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Glucose Metabolism ◽  
Polyunsaturated Fatty Acids ◽  
Kinase Activity ◽  
Control Diet ◽  
Metabolizable Energy ◽  
Oral Glucose ◽  
Phosphatidylinositol 3 Kinase ◽  
Long Chain ◽  
Phosphatidylinositol 3

We examined whether a low amount of dietary long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) modulated phosphatidylinositol 3′-kinase (PI 3-kinase) activity and downstream Akt phosphorylation differently in normal or insulin-resistant rats. Rats were fed for 28 days with either a control diet containing 14.6% of metabolizable energy (ME) as peanut-rape oil (PR) or an n-3 diet where 4.9% of ME as PR was replaced by fish oil. Over the last 5 days, rats received 9‰ NaCl or dexamethasone (1 mg/kg). Insulin stimulation of both PI 3-kinase activity and Akt serine473 phosphorylation and modulation of GLUT4 content were studied in liver, muscle, and adipose tissue (AT). Glucose tolerance and insulin sensitivity were determined by an oral glucose challenge. In muscle and AT, LC n-3 PUFA abolished insulin-stimulated PI 3-kinase activity. These effects were not paralleled by defects in Akt serine473 phosphorylation, which was even increased in AT. Dexamethasone abolished insulin-stimulated PI 3-kinase activity in all tissues, whereas Akt serine473 phosphorylation was markedly reduced in muscle but unaltered in liver and AT. Such tissue-specific dissociating effects of LC n-3 PUFA on PI 3-kinase/Akt activation took place without alteration of glucose metabolism. Maintenance of a normal glucose metabolism by the n-3 diet despite abolition of PI 3-kinase activation was likely explained by a compensatory downstream Akt serine473 phosphorylation. The inability of LC n-3 PUFA to prevent insulin resistance by dexamethasone could result from the lack of such a dissociation.

scholarly journals Insulin Hypersensitivity and Resistance to Streptozotocin-Induced Diabetes in Mice Lacking PTEN in Adipose Tissue

2005 ◽  
Vol 25 (6) ◽  
pp. 2498-2510 ◽  
Author(s):  
Christine Kurlawalla-Martinez ◽  
Bangyan Stiles ◽  
Ying Wang ◽  
Sherin U. Devaskar ◽  
Barbara B. Kahn ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Negative Regulator ◽  
Metabolic Effects ◽  
Tissue Loss ◽  
Phosphatidylinositol 3 Kinase ◽  
Streptozotocin Induced Diabetes ◽  
Phosphatidylinositol 3

ABSTRACT In adipose tissue, insulin controls glucose and lipid metabolism through the intracellular mediators phosphatidylinositol 3-kinase and serine-threonine kinase AKT. Phosphatase and a tensin homolog deleted from chromosome 10 (PTEN), a negative regulator of the phosphatidylinositol 3-kinase/AKT pathway, is hypothesized to inhibit the metabolic effects of insulin. Here we report the generation of mice lacking PTEN in adipose tissue. Loss of Pten results in improved systemic glucose tolerance and insulin sensitivity, associated with decreased fasting insulin levels, increased recruitment of the glucose transporter isoform 4 to the cell surface in adipose tissue, and decreased serum resistin levels. Mutant animals also exhibit increased insulin signaling and AMP kinase activity in the liver. Pten mutant mice are resistant to developing streptozotocin-induced diabetes. Adipose-specific Pten deletion, however, does not alter adiposity or plasma fatty acids. Our results demonstrate that in vivo PTEN is a potent negative regulator of insulin signaling and insulin sensitivity in adipose tissue. Furthermore, PTEN may be a promising target for nutritional and/or pharmacological interventions aimed at reversing insulin resistance.

Possibility of distinct insulin-signaling pathways beyond phosphatidylinositol 3-kinase-mediating glucose transport and lipogenesis

Diabetes ◽  
1998 ◽  
Vol 47 (2) ◽  
pp. 179-185 ◽  
Author(s):  
R. W. Stevenson ◽  
D. K. Kreutter ◽  
K. M. Andrews ◽  
P. E. Genereux ◽  
E. M. Gibbs
Keyword(s):  
Signaling Pathways ◽  
Glucose Transport ◽  
Insulin Signaling ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

scholarly journals Differential Effects of Short-term Ketogenic, High Fat and Fructose-enriched Diets on Metabolic Parameters in Mice (P08-042-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Natalia Cortez ◽  
John Solitro ◽  
Brian Hong ◽  
Emily Villarreal ◽  
Gerardo Mackenzie
Keyword(s):  
Body Composition ◽  
Body Weight ◽  
Grip Strength ◽  
Glucose Homeostasis ◽  
Control Diet ◽  
Oral Glucose ◽  
High Fat ◽  
Carbohydrate Source ◽  
Strength Performance ◽  
Glucose Levels

Abstract Objectives Dietary composition influences multiple facets of human health and is inextricably linked to chronic metabolic conditions such as obesity, type 2 diabetes, cardiovascular disease and cancer. Thus, the objective of this study was to evaluate the effects of a ketogenic (KD), a high fat (HF), and a fructose-enriched (FR) diets on glucose homeostasis, body composition and grip strength performance in mice. Methods Healthy C57BL/6 J mice (5–6 mice/group) were fed, either a control diet containing approximately 16% total calories from fat (CT), a diet containing 89% fat (KD), a diet with 50% total calories from fat (HF), or a diet with 32% fructose as carbohydrate source (FR). All diets contained 10% protein and all mice were fed ad libitum for 8 weeks. At baseline and 8 weeks, we evaluated body composition using NMR relaxometry, grip strength, non-fasting glucose levels, and ketone levels. In addition, oral glucose tolerance test (OGTT) was conducted by administering glucose by oral gavage (1 g/kg body weight) after 15 hour-fasting and blood glucose levels were measured at 0, 30, 60, 90, and 120 min after glucose administration. Results All mice, irrespectively of their experimental diet groups, increased their body weight, fat mass and adiposity without significant differences among them. After 4 weeks, the HF (P < 0.05) and FR (P < 0.01) groups had significantly higher glucose levels than control. At 8 weeks, the KD groups showed an improved glucose homeostasis compared to CT group, as determined by OGTT. Moreover, compared to the CT group, grip strength performance increased (although did not reached significance) in the KD group (P = 0.054), and decreased in the FR group (P < 0.05). Moreover, when compared to their respective baseline values, grip strength performance increased in KD-fed mice and decreased in FR-fed mice, but differences among them were not statistically significant (P = 0.07). Conclusions Our preliminary findings indicate that altering macronutrient composition can lead to metabolic and physiological changes. Among the three diets tested, the KD showed an improved glucose utilization and better grip strength performance in mice. Additional mechanistic studies are warranted to better understand these metabolic differences among the experimental diets. Funding Sources funds from the University of California, Davis.

scholarly journals Inhibition of phosphatidylinositol 3-kinase activity by association with 14-3-3 proteins in T cells.

1995 ◽  
Vol 92 (22) ◽  
pp. 10142-10146 ◽  
Author(s):  
N. Bonnefoy-Berard ◽  
Y. C. Liu ◽  
M. von Willebrand ◽  
A. Sung ◽  
C. Elly ◽  
...  
Keyword(s):  
T Cells ◽  
Kinase Activity ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

Phosphatidylinositol 3-kinase activation is mediated by high-affinity interactions between distinct domains within the p110 and p85 subunits

1994 ◽  
Vol 14 (1) ◽  
pp. 42-49
Author(s):  
K H Holt ◽  
L Olson ◽  
W S Moye-Rowley ◽  
J E Pessin
Keyword(s):  
Gene Fusion ◽  
Kinase Activity ◽  
Expression System ◽  
Sh2 Domain ◽  
Full Length ◽  
Transactivation Domain ◽  
Phosphatidylinositol 3 Kinase ◽  
Sh2 Domains ◽  
Amino Terminal ◽  
Phosphatidylinositol 3

Domains of interaction between the p85 and p110 subunits of phosphatidylinositol 3-kinase (PI 3-kinase) were studied with the yeast two-hybrid expression system. A gene fusion between the GAL4 transactivation domain and p85 activated transcription from a GAL1-lacZ reporter gene when complemented with a gene fusion between the GAL4 DNA binding domain and p110. To define subdomains responsible for this interaction, a series of p85 deletion mutants were analyzed. A 192-amino-acid inter-SH2 (IS) fragment (residues 429 to 621) was the smallest determinant identified that specifically associated with p110. In analogous experiments, the subdomain within p110 responsible for interaction with p85 was localized to an EcoRI fragment encoding the amino-terminal 127 residues. Expression of these two subdomains [p85(IS) with p110RI] resulted in 100-fold greater reporter activity than that obtained with full-length p85 and p110. Although the p85(IS) domain conferred a strong interaction with the p110 catalytic subunit, this region was not sufficient to impart phosphotyrosine peptide stimulation of PI 3-kinase activity. In contrast, coexpression of the p110 subunit with full-length p85 or with constructs containing the IS sequences flanked by both SH2 domains of p85 [p85(n/cSH2)] or either of the individual SH2 domains [p85(nSH2+IS) or p85(IS+cSH2)] resulted in PI 3-kinase activity that was activated by a phosphotyrosine peptide. These data suggest that phosphotyrosine peptide binding to either SH2 domain generates an intramolecular signal propagated through the IS region to allosterically activate p110.

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