AMPK-mTOR pathway is involved in glucose-modulated amino acid sensing and utilization in the mammary glands of lactating goats

Chronically high insulin levels and increased circulating free fatty acids released from adipose tissue through lipolysis are two features associated with insulin resistance. The relationship between chronic insulin exposure and adipocyte lipolysis has been unclear. In the present study we found that chronic insulin exposure in 3T3-L1 adipocytes, as well as in mouse primary adipocytes, increased basal lipolysis rates. This effect of insulin on lipolysis was only observed when the mammalian target of rapamycin (mTOR) pathway was inhibited by rapamycin in the adipocytes. In addition, amino acid deprivation in adipocytes phenocopied the effect of rapamycin in permitting the stimulation of lipolysis by chronic insulin exposure. The phosphatidylinositol 3-kinase-Akt pathway does not appear to be involved in this insulin effect. Furthermore, we found that triacylglycerol hydrolase (TGH) activity was required for the stimulation of lipolysis by combined exposure to insulin and rapamycin. Therefore, we propose that nutrient sufficiency, mediated by an mTOR pathway, suppresses TGH-dependent lipolysis stimulated by chronic insulin exposure in adipocytes.

Download Full-text

Self-Healing Metallacycle-Cored Supramolecular Polymers Based on a Metal–Salen Complex Constructed by Orthogonal Metal Coordination and Host–Guest Interaction with Amino Acid Sensing

ACS Macro Letters ◽

10.1021/acsmacrolett.1c00228 ◽

2021 ◽

pp. 873-879

Author(s):

Qian Zhang ◽

Feng Chen ◽

Xi Shen ◽

Tian He ◽

Huayu Qiu ◽

...

Keyword(s):

Amino Acid ◽

Metal Coordination ◽

Supramolecular Polymers ◽

Self Healing ◽

Salen Complex ◽

Amino Acid Sensing ◽

Metal Salen Complex

Download Full-text

Role of amino acid transporters in amino acid sensing

American Journal of Clinical Nutrition ◽

10.3945/ajcn.113.070086 ◽

2013 ◽

Vol 99 (1) ◽

pp. 223S-230S ◽

Cited By ~ 133

Author(s):

Peter M Taylor

Keyword(s):

Amino Acid ◽

Amino Acid Transporters ◽

Amino Acid Sensing

Download Full-text

Implications of amino acid sensing and dietary protein to the aging process

Experimental Gerontology ◽

10.1016/j.exger.2018.11.021 ◽

2019 ◽

Vol 115 ◽

pp. 69-78 ◽

Cited By ~ 11

Author(s):

Oleh Lushchak ◽

Olha M. Strilbytska ◽

Ihor Yurkevych ◽

Alexander M. Vaiserman ◽

Kenneth B. Storey

Keyword(s):

Amino Acid ◽

Dietary Protein ◽

Aging Process ◽

Amino Acid Sensing

Download Full-text

Leucine metabolism in lactating and dry goats: effect of insulin and substrate availability

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1993.265.3.e402 ◽

1993 ◽

Vol 265 (3) ◽

pp. E402-E413 ◽

Cited By ~ 3

Author(s):

S. Tesseraud ◽

J. Grizard ◽

E. Debras ◽

I. Papet ◽

Y. Bonnet ◽

...

Keyword(s):

Protein Synthesis ◽

Amino Acid ◽

Protein Degradation ◽

Whole Body ◽

Initial Slope ◽

Sensitivity Index ◽

Early Lactation ◽

Dry Period ◽

Body Protein ◽

Lactating Goats

Early lactating goats show insulin resistance with respect to extramammary glucose utilization. However, much less is known about the two major factors, insulin and plasma amino acid concentration, that regulate protein metabolism in lactating goats. To examine this question, the in vivo effect of acute insulin was studied in goats during early lactation (12-31 days postpartum), midlactation (98-143 days postpartum), and the dry period (approximately 1 yr postpartum). Insulin was infused (at 0.36 or 1.79 nmol/min) under euglycemic and eukaliemic clamps. In addition, appropriate amino acid infusion was used to blunt insulin-induced hypoaminoacidemia or to create hyperaminoacidemia and maintain this condition under insulin treatment. Leucine kinetics were assessed using a primed continuous infusion of L-[1-14C]-leucine, which started 2.5 h before insulin. In all animals the insulin treatments failed to stimulate the nonoxidative leucine disposal (an estimate of whole body protein synthesis) under both euaminoacidemic and hyperaminoacidemic conditions. Thus, in goat as well as humans, infusion of insulin fails to stimulate protein synthesis even when combined with a substantially increased provision of amino acids. In contrast, insulin treatments caused a dose-dependent inhibition of the endogenous leucine appearance (an estimate of whole body protein degradation). Under euaminoacidemia the initial slope from the plot of the endogenous leucine appearance as a function of plasma insulin (an insulin sensitivity index) was steeper during early lactation than when compared with the dry period. A similar trend occurred during midlactation but not to any significant degree. These differences were abolished under hyperaminoacidemia. It was concluded that the ability of physiological insulin to inhibit protein degradation was improved during lactation, demonstrating a clear-cut dissociation between the effects of insulin on protein and glucose metabolism. This adaptation no doubt may provide a mechanism to save body protein.

Download Full-text

Effect of hyperinsulinemia and hyperaminoacidemia on muscle and liver protein synthesis in lactating goats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.267.6.e877 ◽

1994 ◽

Vol 267 (6) ◽

pp. E877-E885 ◽

Cited By ~ 6

Author(s):

I. Tauveron ◽

D. Larbaud ◽

C. Champredon ◽

E. Debras ◽

S. Tesseraud ◽

...

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Amino Acid ◽

Skeletal Muscles ◽

Constant Infusion ◽

Acid Mixture ◽

Liver Protein ◽

Group I ◽

Lactating Goats ◽

Group A

The experiment was carried out to clarify the roles of insulin and amino acids on protein synthesis in fed lactating goats (30 days postpartum). Protein synthesis in the liver and various skeletal muscles was assessed after an intravenous injection of a large dose of unlabeled valine containing a tracer dose of L-[2,3,4-3H]valine. The animals were divided into three groups. Group I was infused with insulin (1.7 mumol/min) for 2.5 h under glucose, potassium, and amino acid replacement. Group A was infused with an amino acid mixture to create stable hyperaminoacidemia for 2.5 h. Group C animals were controls. The fractional synthesis rates (FSR) were 31.5 +/- 2.2, 6.5 +/- 0.4, 4.3 +/- 0.8, 4.0 +/- 1.2, 3.9 +/- 1.2, and 3.6 +/- 0.4%/day (SD) in liver, masseter, diaphragm, anconeus, semitendinosus, and longissimus dorsi, respectively, for group C. Neither hyperinsulinemia in group I nor hyperaminoacidemia in group A had not affected by hyperinsulinemia but was stimulated by hyperaminoacidemia (+30%, P < 0.05). In contrast to previous experiments in which a labeled amino acid was constantly infused, this study revealed a stimulating effect of amino acids on protein synthesis in the liver but not in skeletal muscles. As previously observed in studies with the constant-infusion method, insulin had no effect on protein synthesis.

Download Full-text

Activation of the SPS Amino Acid-Sensing Pathway in Saccharomyces cerevisiae Correlates with the Phosphorylation State of a Sensor Component, Ptr3

Molecular and Cellular Biology ◽

10.1128/mcb.00929-07 ◽

2007 ◽

Vol 28 (2) ◽

pp. 551-563 ◽

Cited By ~ 47

Author(s):

Zhengchang Liu ◽

Janet Thornton ◽

Mário Spírek ◽

Ronald A. Butow

Keyword(s):

Saccharomyces Cerevisiae ◽

Amino Acids ◽

Amino Acid ◽

Nuclear Translocation ◽

Proteolytic Processing ◽

Casein Kinase I ◽

Positive Regulators ◽

Amino Acid Permeases ◽

Amino Acid Sensing ◽

Amino Acid Sensor

ABSTRACT Cells of the budding yeast Saccharomyces cerevisiae sense extracellular amino acids and activate expression of amino acid permeases through the SPS-sensing pathway, which consists of Ssy1, an amino acid sensor on the plasma membrane, and two downstream factors, Ptr3 and Ssy5. Upon activation of SPS signaling, two transcription factors, Stp1 and Stp2, undergo Ssy5-dependent proteolytic processing that enables their nuclear translocation. Here we show that Ptr3 is a phosphoprotein whose hyperphosphorylation is increased by external amino acids and is dependent on Ssy1 but not on Ssy5. A deletion mutation in GRR1, encoding a component of the SCFGrr1 E3 ubiquitin ligase, blocks amino acid-induced hyperphosphorylation of Ptr3. We found that two casein kinase I (CKI) proteins, Yck1 and Yck2, previously identified as positive regulators of SPS signaling, are required for hyperphosphorylation of Ptr3. Loss- and gain-of-function mutations in PTR3 result in decreased and increased Ptr3 hyperphosporylation, respectively. We found that a defect in PP2A phosphatase activity leads to the hyperphosphorylation of Ptr3 and constitutive activation of SPS signaling. Two-hybrid analysis revealed interactions between the N-terminal signal transduction domain of Ssy1 with Ptr3 and Yck1. Our findings reveal that CKI and PP2A phosphatase play antagonistic roles in SPS sensing by regulating Ptr3 phosphorylation.

Download Full-text