scholarly journals Fiber Type-Specific Differences in Glucose Uptake by Single Fibers From Skeletal Muscles of 9- and 25-Month-Old Rats

2012 ◽  
Vol 67 (12) ◽  
pp. 1286-1294 ◽  
Author(s):  
J. G. MacKrell ◽  
E. B. Arias ◽  
G. D. Cartee
2018 ◽  
Vol 43 (8) ◽  
pp. 795-805 ◽  
Author(s):  
Kentaro Oki ◽  
Edward B. Arias ◽  
Makoto Kanzaki ◽  
Gregory D. Cartee

5′ AMP-activated protein kinase (AMPK) activation may be part of the exercise-induced process that enhances insulin sensitivity. Independent of exercise, acute prior treatment of skeletal muscles isolated from young rats with a pharmacological AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), causes subsequently improved insulin-stimulated glucose uptake (GU). However, efficacy of a single prior AICAR exposure on insulin-stimulated GU in muscles from old animals has not been studied. The purpose of this study was to determine whether brief, prior exposure to AICAR (3.5 h before GU assessment) leads to subsequently increased GU in insulin-stimulated skeletal muscles from old rats. Epitrochlearis muscles from 24-month-old male rats were isolated and initially incubated ±AICAR (60 min), followed by incubation without AICAR (3 h), then incubation ±insulin (50 min). Muscles were assessed for GU (via 3-O-methyl-[3H]-glucose accumulation) and site-specific phosphorylation of key proteins involved in enhanced GU, including AMPK, Akt, and Akt substrate of 160 kDa (AS160), via Western blotting. Prior ex vivo AICAR treatment resulted in greater GU by insulin-stimulated muscles from 24-month-old rats. Prior AICAR treatment also resulted in greater phosphorylation of AMPK (T172) and AS160 (S588, T642, and S704). Glucose transporter type 4 (GLUT4) protein abundance was unaffected by prior AICAR and/or insulin treatment. These findings demonstrate that skeletal muscles from older rats are susceptible to enhanced insulin-stimulated GU after brief activation of AMPK by prior AICAR. Consistent with earlier research using muscles from young rodents, increased phosphorylation of AS160 is implicated in this effect, which was not attributable to altered GLUT4 glucose transporter protein abundance.


1991 ◽  
Vol 260 (6) ◽  
pp. H1795-H1801 ◽  
Author(s):  
P. O. Iversen ◽  
G. Nicolaysen

A marked regional heterogeneity in blood flow at the level of large arterioles or small arteries is present within single skeletal muscles both in the dog and in the rabbit. A corresponding regional heterogeneity in metabolic activity could explain this phenomenon. We studied the correlation between regional blood flow and regional uptake of glucose within single muscles. Blood flow and glucose uptake were measured using the microsphere technique and the deoxyglucose method, respectively. Blood flow and glucose uptake were determined in 0.25-g regions from resting and stimulated muscles in anesthetized rabbits. Under resting conditions, no correlation between regional blood flow and regional glucose uptake (P greater than 0.05, 12 muscles) was observed. During stimulation, regional blood flow was positively correlated (0.4 less than r less than 0.6, P less than 0.05, 12 muscles) with regional glucose uptake. The coefficients of variation for regional blood flow and regional glucose uptake averaged approximately 0.35 and 0.23, respectively, both at rest and during stimulation. Specific fiber type distributions could not explain either the regional heterogeneity in blood flow or in glucose uptake. We conclude that regional blood flow within single skeletal muscles is not strongly linked to regional uptake of glucose. Both variables show considerable heterogeneity.


2016 ◽  
Vol 311 (5) ◽  
pp. E818-E824 ◽  
Author(s):  
Gregory D. Cartee ◽  
Edward B. Arias ◽  
Carmen S. Yu ◽  
Mark W. Pataky

One exercise session can induce subsequently elevated insulin sensitivity that is largely attributable to greater insulin-stimulated glucose uptake by skeletal muscle. Because skeletal muscle is a heterogeneous tissue comprised of diverse fiber types, our primary aim was to determine exercise effects on insulin-independent and insulin-dependent glucose uptake by single fibers of different fiber types. We hypothesized that each fiber type featuring elevated insulin-independent glucose uptake immediately postexercise (IPEX) would be characterized by increased insulin-dependent glucose uptake at 3.5 h postexercise (3.5hPEX). Rat epitrochlearis muscles were isolated and incubated with 2-[3H]deoxyglucose. Muscles from IPEX and sedentary (SED) controls were incubated without insulin. Muscles from 3.5hPEX and SED controls were incubated ± insulin. Glucose uptake (2-[3H]deoxyglucose accumulation) and fiber type (myosin heavy chain isoform expression) were determined for single fibers dissected from the muscles. Major new findings included the following: 1) insulin-independent glucose uptake was increased IPEX in single fibers of each fiber type (types I, IIA, IIB, IIBX, and IIX), 2) glucose uptake values from insulin-stimulated type I and IIA fibers exceeded the values for the other fiber types, 3) insulin-stimulated glucose uptake for type IIX exceeded IIB fibers, and 4) the 3.5hPEX group vs. SED had greater insulin-stimulated glucose uptake in type I, IIA, IIB, and IIBX but not type IIX fibers. Insulin-dependent glucose uptake was increased at 3.5hPEX in each fiber type except for IIX fibers, although insulin-independent glucose uptake was increased IPEX in all fiber types (including type IIX). Single fiber analysis enabled the discovery of this fiber type-related difference for postexercise, insulin-stimulated glucose uptake.


2015 ◽  
Vol 308 (3) ◽  
pp. E223-E230 ◽  
Author(s):  
Carlos M. Castorena ◽  
Edward B. Arias ◽  
Naveen Sharma ◽  
Jonathan S. Bogan ◽  
Gregory D. Cartee

To fully understand skeletal muscle at the cellular level, it is essential to evaluate single muscle fibers. Accordingly, the major goals of this study were to determine if there are fiber type-related differences in single fibers from rat skeletal muscle for: 1) contraction-stimulated glucose uptake and/or 2) the abundance of GLUT4 and other metabolically relevant proteins. Paired epitrochlearis muscles isolated from Wistar rats were either electrically stimulated to contract (E-Stim) or remained resting (No E-Stim). Single fibers isolated from muscles incubated with 2-deoxy-d-[3H]glucose (2-DG) were used to determine fiber type [myosin heavy chain (MHC) isoform protein expression], 2-DG uptake, and abundance of metabolically relevant proteins, including the GLUT4 glucose transporter. E-Stim, relative to No E-Stim, fibers had greater ( P < 0.05) 2-DG uptake for each of the isolated fiber types (MHC-IIa, MHC-IIax, MHC-IIx, MHC-IIxb, and MHC-IIb). However, 2-DG uptake for E-Stim fibers was not significantly different among these five fiber types. GLUT4, tethering protein containing a UBX domain for GLUT4 (TUG), cytochrome c oxidase IV (COX IV), and filamin C protein levels were significantly greater ( P < 0.05) in MHC-IIa vs. MHC-IIx, MHC-IIxb, or MHC-IIb fibers. TUG and COX IV in either MHC-IIax or MHC-IIx fibers exceeded values for MHC-IIxb or MHC-IIb fibers. GLUT4 levels for MHC-IIax fibers exceeded MHC-IIxb fibers. GLUT4, COX IV, filamin C, and TUG abundance in single fibers was significantly ( P < 0.05) correlated with each other. Differences in GLUT4 abundance among the fiber types were not accompanied by significant differences in contraction-stimulated glucose uptake.


AGE ◽  
2012 ◽  
Vol 35 (3) ◽  
pp. 573-582 ◽  
Author(s):  
Yuanyuan Xiao ◽  
Naveen Sharma ◽  
Edward B. Arias ◽  
Carlos M. Castorena ◽  
Gregory D. Cartee

2016 ◽  
Vol 310 (4) ◽  
pp. E276-E288 ◽  
Author(s):  
Stefan R. Hargett ◽  
Natalie N. Walker ◽  
Susanna R. Keller

The related Rab GTPase-activating proteins (Rab GAPs) AS160 and Tbc1d1 regulate the trafficking of the glucose transporter GLUT4 that controls glucose uptake in muscle and fat cells and glucose homeostasis. AS160- and Tbc1d1-deficient mice exhibit different adipocyte- and skeletal muscle-specific defects in glucose uptake, GLUT4 expression and trafficking, and glucose homeostasis. A recent study analyzed male mice with simultaneous deletion of AS160 and Tbc1d1 (AS160−/−/Tbc1d1−/− mice). Herein, we describe abnormalities in male and female AS160−/−/Tbc1d1−/− mice on another strain background. We confirm the earlier observation that GLUT4 expression and glucose uptake defects of single-knockout mice join in AS160−/−/Tbc1d1−/− mice to affect all skeletal muscle and adipose tissues. In large mixed fiber-type skeletal muscles, changes in relative basal GLUT4 plasma membrane association in AS160−/− and Tbc1d1−/− mice also combine in AS160−/−/Tbc1d1−/− mice. However, we found different glucose uptake abnormalities in isolated skeletal muscles and adipocytes than reported previously, resulting in different interpretations of how AS160 and Tbc1d1 regulate GLUT4 translocation to the cell surface. In support of a larger role for AS160 in glucose homeostasis, in contrast with the previous study, we find similarly impaired glucose and insulin tolerance in AS160−/−/Tbc1d1−/− and AS160−/− mice. However, in vivo glucose uptake abnormalities in AS160−/−/Tbc1d1−/− skeletal muscles differ from those observed previously in AS160−/− mice, indicating additional defects due to Tbc1d1 deletion. Similar to AS160- and Tbc1d1-deficient mice, AS160−/−/Tbc1d1−/− mice show sex-specific abnormalities in glucose and energy homeostasis. In conclusion, our study supports nonredundant functions for AS160 and Tbc1d1.


2012 ◽  
pp. 575-586 ◽  
Author(s):  
T. SOUKUP ◽  
V. SULIMENKO ◽  
V. MARKOVÁ ◽  
K. KOPECKÁ ◽  
G. ZACHAŘOVÁ ◽  
...  

We have investigated expression of skeletal calsequestrin (CSQ1) and fiber type composition in normal and regenerated fast and slow skeletal muscles and in the left heart ventricles of euthyroid (EU), hypothyroid (HY) and hyperthyroid (TH) adult inbred Lewis strain rats. The CSQ1 level was determined by SDS-PAGE followed by Western blot analysis. CSQ1 gene expression was assessed using reverse transcription and subsequent real time polymerase chain reaction. Muscle regeneration was achieved by intramuscular grafting of either soleus or extensor digitorum longus (EDL) from 3- to 4-week-old rats to either EDL or soleus muscle of 2-month-old rats. The fiber type composition was assessed by a stereological method applied to stained muscle cross sections. We found that the protein and mRNA levels for CSQ1 were highest in the EDL muscle, the relative CSQ1 protein levels in the soleus muscle were two times lower and the transcript levels more than 5 times lower compared to the EDL. In the left heart ventricle, protein isoform and CSQ1 transcript were also present, although at protein level, CSQ1 was hardly detectable. TH status increased and HY status decreased the expression of CSQ1 in the EDL, but its relative levels in the soleus and in the heart did not change. The regenerated soleus transplanted into EDL, as well as EDL transplanted into soleus exhibited protein and mRNA levels of CSQ1 corresponding to the host muscle and not to the graft source. TH status increased the percentages of the fastest 2X/D and 2B fibers at the expense of slow type 1 and fast 2A fibers in the EDL and that of fast 2A fibers in the soleus at the expense of slow type 1 fibers. HY status led to converse fiber type changes. We suggest that the observed changes in CSQ1 levels in TH and HY compared to EU rats can be related to fiber type changes caused by alteration of the thyroid status rather than to the direct effect of thyroid hormones on CSQ1 gene expression.


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