scholarly journals Skeletal Muscle Insulin Sensitivity Show Circadian Rhythmicity Which Is Independent of Exercise Training Status

2018 ◽  
Vol 9 ◽  
Author(s):  
Astrid L. Basse ◽  
Emilie Dalbram ◽  
Louise Larsson ◽  
Zach Gerhart-Hines ◽  
Juleen R. Zierath ◽  
...  
1986 ◽  
Vol 250 (5) ◽  
pp. E570-E575
Author(s):  
G. K. Grimditch ◽  
R. J. Barnard ◽  
S. A. Kaplan ◽  
E. Sternlicht

We examined the hypothesis that the exercise training-induced increase in skeletal muscle insulin sensitivity is mediated by adaptations in insulin binding to sarcolemmal (SL) insulin receptors. Insulin binding studies were performed on rat skeletal muscle SL isolated from control and trained rats. No significant differences were noted between groups in body weight or fat. An intravenous glucose tolerance test showed an increase in whole-body insulin sensitivity with training, and specific D-glucose transport studies on isolated SL vesicles indicated that this was due in part to adaptations in skeletal muscle. Enzyme marker analyses revealed no differences in yield, purity, or contamination of SL membranes between the two groups. Scatchard analyses indicated no significant differences in the number of insulin binding sites per milligram SL protein on the high-affinity (15.0 +/- 4.1 vs. 18.1 +/- 6.4 X 10(9)) or on the low-affinity portions (925 +/- 80 vs. 884 +/- 106 X 10(9)) of the curves. The association constants of the high-affinity (0.764 +/- 0.154 vs. 0.685 +/- 0.264 X 10(9) M-1) and of the low affinity sites (0.0096 +/- 0.0012 vs. 0.0102 +/- 0.0012 X 10(9) M-1) also were similar. These results do not support the hypothesis that the increased sensitivity to insulin after exercise training is due to changes in SL insulin receptor binding.


1996 ◽  
Vol 80 (6) ◽  
pp. 1963-1967 ◽  
Author(s):  
N. Nakai ◽  
Y. Shimomura ◽  
N. Ohsaki ◽  
J. Sato ◽  
Y. Oshida ◽  
...  

We examined the effects of exercise training initiated before maturation or after maturation on insulin sensitivity and glucose transporter GLUT-4 content in membrane fractions of skeletal muscle. Female Wistar rats (4 wk of age) were divided into sedentary and exercise-trained groups. At 12 wk of age, a subset of the trained animals (Tr) was killed along with a subset of sedentary controls (Sed). One-half of the remaining sedentary animals remained sedentary (Sed-Sed) while the other half began exercise training (Sed-Tr). The remaining rats in the original trained group continued to train (Tr-Tr). Euglycemic clamp (insulin infusion rate at 6 mU.kg body wt-1. min-1) was performed at 4, 12, and 27 wk. After euglycemic clamp in all animals except the 4-wk-old, hindlimb (gastrocnemius and part of quadriceps) muscles were removed for preparation of membrane fractions. In sedentary rats, glucose infusion rate (GIR) during euglycemic clamp was decreased from 15.9 mg.kg-1.min-1 at 4 wk of age to 9.8 mg.kg-1.min-1 at 12 wk of age and 9.1 mg.kg-1.min-1 at 27 wk of age. In exercise-trained rats, the GIR was not significantly decreased by maturation (at 12 wk) and further aging (at 27 wk). Initiation of exercise after maturation restored the GIR at 27 wk of age to the same levels as these for the corresponding exercise-trained rats. GLUT-4 content in plasma and intracellular membrane fractions of hindlimb muscle obtained just after euglycemic clamp showed the same trend as the results of GIR. These results suggest that exercise training prevented the maturation-induced decrease in insulin sensitivity. Improvement of insulin sensitivity caused by exercise training was attributed, at least in part, to the increase in insulin-sensitive GLUT-4 on the plasma membrane in skeletal muscle.


2020 ◽  
Author(s):  
Feifan Guo ◽  
Yuguo Niu ◽  
Haizhou Jiang ◽  
Hanrui Yin ◽  
Fenfen Wang ◽  
...  

Abstract The current study aimed to investigate the role of endoplasmic reticulum aminopeptidase 1 (ERAP1), a novel hepatokine, in whole-body glucose metabolism. Here, we found that hepatic ERAP1 levels were increased in insulin-resistant leptin-receptor-mutated (db/db) and high-fat diet (HFD)-fed mice. Consistently, hepatic ERAP1 overexpression attenuated skeletal muscle (SM) insulin sensitivity, whereas knockdown ameliorated SM insulin resistance. Furthermore, serum and hepatic ERAP1 levels were positively correlated, and recombinant mouse ERAP1 or conditioned medium with high ERAP1 content (CM-ERAP1) attenuated insulin signaling in C2C12 myotubes, and CM-ERAP1 or HFD-induced insulin resistance was blocked by ERAP1 neutralizing antibodies. Mechanistically, ERAP1 reduced ADRB2 expression and interrupted ADRB2-dependent signaling in C2C12 myotubes. Finally, ERAP1 inhibition via global knockout or the inhibitor thimerosal improved insulin sensitivity. Together, ERAP1 is a hepatokine that impairs SM and whole-body insulin sensitivity, and its inhibition might provide a therapeutic strategy for diabetes, particularly for those with SM insulin resistance.


2011 ◽  
Vol 14 (2) ◽  
pp. 153-161 ◽  
Author(s):  
Yolanda Gómez-Pérez ◽  
Magdalena Gianotti ◽  
Ana M. Proenza ◽  
Isabel Lladó

2020 ◽  
Vol 21 (4) ◽  
pp. 1514 ◽  
Author(s):  
Paul T. Reidy ◽  
Ziad S. Mahmassani ◽  
Alec I. McKenzie ◽  
Jonathan J. Petrocelli ◽  
Scott A. Summers ◽  
...  

Intramuscular lipid accumulation has been associated with insulin resistance (IR), aging, diabetes, dyslipidemia, and obesity. A substantial body of evidence has implicated ceramides, a sphingolipid intermediate, as potent antagonists of insulin action that drive insulin resistance. Indeed, genetic mouse studies that lower ceramides are potently insulin sensitizing. Surprisingly less is known about how physical activity (skeletal muscle contraction) regulates ceramides, especially in light that muscle contraction regulates insulin sensitivity. The purpose of this review is to critically evaluate studies (rodent and human) concerning the relationship between skeletal muscle ceramides and IR in response to increased physical activity. Our review of the literature indicates that chronic exercise reduces ceramide levels in individuals with obesity, diabetes, or hyperlipidemia. However, metabolically healthy individuals engaged in increased physical activity can improve insulin sensitivity independent of changes in skeletal muscle ceramide content. Herein we discuss these studies and provide context regarding the technical limitations (e.g., difficulty assessing the myriad ceramide species, the challenge of obtaining information on subcellular compartmentalization, and the paucity of flux measurements) and a lack of mechanistic studies that prevent a more sophisticated assessment of the ceramide pathway during increased contractile activity that lead to divergences in skeletal muscle insulin sensitivity.


Diabetes ◽  
2018 ◽  
Vol 67 (11) ◽  
pp. 2183-2198 ◽  
Author(s):  
Tingting Geng ◽  
Ya Liu ◽  
Yetao Xu ◽  
Ying Jiang ◽  
Na Zhang ◽  
...  

2019 ◽  
Vol 3 (s1) ◽  
pp. 40-40
Author(s):  
George Schweitzer ◽  
Monica Kearney ◽  
Gordon Smith ◽  
Samuel Klein

OBJECTIVES/SPECIFIC AIMS: People with metabolically abnormal obesity (MAO), defined as those with insulin resistance and high intrahepatic triglyceride, are at high risk for developing type 2 diabetes and cardiovascular disease. Weight loss through reduced energy intake and increased physical activity has profound impacts on improving cardiometabolic function. However, the specific additional effects of exercise training with diet-induced weight loss on metabolic function are equivocal. METHODS/STUDY POPULATION: A comparative trial is ongoing in MAO adults undergoing 8-10% weight loss induced by a very-low fat plant-based (PB) diet with structured exercise training (n=8) compared to the same weight loss induced by the PB diet alone (n=3). RESULTS/ANTICIPATED RESULTS: Preliminary results indicate that, PB diet with or without exercise training results in significant weight loss concomitant with enhanced insulin sensitivity, reduced intrahepatic triglyceride, reduced 24-hour postprandial glucose response, reduced fat mass, and reduced diastolic blood pressure. Those undergoing PB diet with exercise training had greater improvements in muscular strength and cardiorespiratory fitness than those undergoing PB diet alone. Differences between intervention groups for other cardiometabolic measures are not yet known. DISCUSSION/SIGNIFICANCE OF IMPACT: Each of the interventions resulted in improved cardiometabolic measures; however the extent of the differences between the interventions is not yet clear. It is hypothesized that compared with weight loss induced by a PB diet, the same weight loss induced by a PB diet and structured exercise training will i) cause greater improvement in skeletal muscle insulin sensitivity, ii) will attenuate the usual decline in muscle mass while increasing strength, and iii) result in greater increases in left ventricular diastolic function. The long-term objective of this proposal is to provide a foundation for future studies evaluating mechanisms for the effects of exercise in cardiometabolic disease prevention and therapy.


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