scholarly journals Skeletal muscle fiber type-selective effects of acute exercise on insulin-stimulated glucose uptake in insulin-resistant, high-fat-fed rats

2019 ◽  
Vol 316 (5) ◽  
pp. E695-E706 ◽  
Author(s):  
Mark W. Pataky ◽  
Carmen S. Yu ◽  
Yilin Nie ◽  
Edward B. Arias ◽  
Manak Singh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Acute Exercise ◽  
Fiber Type ◽  
Single Fiber ◽  
Male Rats ◽  
Type I ◽  
Fiber Types ◽  
High Fat ◽  
Insulin Resistant

Insulin-stimulated glucose uptake (GU) by skeletal muscle is enhanced several hours after acute exercise in rats with normal or reduced insulin sensitivity. Skeletal muscle is composed of multiple fiber types, but exercise’s effect on fiber type-specific insulin-stimulated GU in insulin-resistant muscle was previously unknown. Male rats were fed a high-fat diet (HFD; 2 wk) and were either sedentary (SED) or exercised (2-h exercise). Other, low-fat diet-fed (LFD) rats remained SED. Rats were studied immediately postexercise (IPEX) or 3 h postexercise (3hPEX). Epitrochlearis muscles from IPEX rats were incubated in 2-deoxy-[3H]glucose (2-[3H]DG) without insulin. Epitrochlearis muscles from 3hPEX rats were incubated with 2-[3H]DG ± 100 µU/ml insulin. After single fiber isolation, GU and fiber type were determined. Glycogen and lipid droplets (LDs) were assessed histochemically. GLUT4 abundance was determined by immunoblotting. In HFD-SED vs. LFD-SED rats, insulin-stimulated GU was decreased in type IIB, IIX, IIAX, and IIBX fibers. Insulin-independent GU IPEX was increased and glycogen content was decreased in all fiber types (types I, IIA, IIB, IIX, IIAX, and IIBX). Exercise by HFD-fed rats enhanced insulin-stimulated GU in all fiber types except type I. Single fiber analyses enabled discovery of striking fiber type-specific differences in HFD and exercise effects on insulin-stimulated GU. The fiber type-specific differences in insulin-stimulated GU postexercise in insulin-resistant muscle were not attributable to a lack of fiber recruitment, as indirectly evidenced by insulin-independent GU and glycogen IPEX, differences in multiple LD indexes, or altered GLUT4 abundance, implicating fiber type-selective differences in the cellular processes responsible for postexercise enhancement of insulin-mediated GLUT4 translocation.

scholarly journals Fiber type-specific effects of acute exercise on insulin-stimulated AS160 phosphorylation in insulin-resistant rat skeletal muscle

2019 ◽  
Vol 317 (6) ◽  
pp. E984-E998
Author(s):  
Mark W. Pataky ◽  
Sydney L. Van Acker ◽  
Rhea Dhingra ◽  
Marina M. Freeburg ◽  
Edward B. Arias ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Acute Exercise ◽  
Fiber Type ◽  
Type I ◽  
Fiber Types ◽  
High Fat ◽  
Insulin Resistant ◽  
Specific Effects ◽  
Heterogeneous Tissue ◽  
Whole Muscle

Muscle is a heterogeneous tissue composed of multiple fiber types. Earlier research revealed fiber type-selective postexercise effects on insulin-stimulated glucose uptake (ISGU) from insulin-resistant rats (increased for type IIA, IIB, IIBX, and IIX, but not type I). In whole muscle from insulin-resistant rats, the exercise increase in ISGU is accompanied by an exercise increase in insulin-stimulated AS160 phosphorylation (pAS160), an ISGU-regulating protein. We hypothesized that, in insulin-resistant muscle, the fiber type-selective exercise effects on ISGU would correspond to the fiber type-selective exercise effects on pAS160. Rats were fed a 2-wk high-fat diet (HFD) and remained sedentary (SED) or exercised before epitrochlearis muscles were dissected either immediately postexercise (IPEX) or at 3 h postexercise (3hPEX) using an exercise protocol that previously revealed fiber type-selective effects on ISGU. 3hPEX muscles and SED controls were incubated ± 100µU/mL insulin. Individual myofibers were isolated and pooled on the basis of myosin heavy chain (MHC) expression, and key phosphoproteins were measured. Myofiber glycogen and MHC expression were evaluated in muscles from other SED, IPEX, and 3hPEX rats. Insulin-stimulated pAktSer473 and pAktThr308 were unaltered by exercise in all fiber types. Insulin-stimulated pAS160 was greater for 3hPEX vs. SED on at least one phosphosite (Ser588, Thr642, and/or Ser704) in type IIA, IIBX, and IIB fibers, but not in type I or IIX fibers. Both IPEX and 3hPEX glycogen were decreased versus SED in all fiber types. These results provided evidence that fiber type-specific pAS160 in insulin-resistant muscle may play a role in the previously reported fiber type-specific elevation in ISGU in some, but not all, fiber types.

scholarly journals Novel single skeletal muscle fiber analysis reveals a fiber type-selective effect of acute exercise on glucose uptake

2016 ◽  
Vol 311 (5) ◽  
pp. E818-E824 ◽  
Author(s):  
Gregory D. Cartee ◽  
Edward B. Arias ◽  
Carmen S. Yu ◽  
Mark W. Pataky
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Fiber Type ◽  
Exercise Session ◽  
Type I ◽  
Fiber Types ◽  
Single Fibers ◽  
Fiber Analysis ◽  
New Findings ◽  
Insulin Dependent

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.

Single-fiber expression and fiber-specific adaptability to short-term intense exercise training of Na+-K+-ATPase α- and β-isoforms in human skeletal muscle

2015 ◽  
Vol 118 (6) ◽  
pp. 699-706 ◽  
Author(s):  
V. L. Wyckelsma ◽  
M. J. McKenna ◽  
F. R. Serpiello ◽  
C. R. Lamboley ◽  
R. J. Aughey ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Western Blotting ◽  
Human Skeletal Muscle ◽  
Fiber Type ◽  
Vastus Lateralis ◽  
Single Fiber ◽  
Vastus Lateralis Muscle ◽  
Type I ◽  
Fiber Types ◽  
Functional Roles

The Na+-K+-ATPase (NKA) plays a key role in muscle excitability, but little is known in human skeletal muscle about fiber-type-specific differences in NKA isoform expression or adaptability. A vastus lateralis muscle biopsy was taken in 17 healthy young adults to contrast NKA isoform protein relative abundance between type I and IIa fibers. We further investigated muscle fiber-type-specific NKA adaptability in eight of these adults following 4-wk repeated-sprint exercise (RSE) training, comprising three sets of 5 × 4-s sprints, 3 days/wk. Single fibers were separated, and myosin heavy chain (I and IIa) and NKA (α1–3 and β1–3) isoform abundance were determined via Western blotting. All six NKA isoforms were expressed in both type I and IIa fibers. No differences between fiber types were found for α1-, α2-, α3-, β1-, or β3-isoform abundances. The NKA β2-isoform was 27% more abundant in type IIa than type I fibers ( P < 0.05), with no other fiber-type-specific trends evident. RSE training increased β1 in type IIa fibers (pretraining 0.70 ± 0.25, posttraining 0.84 ± 0.24 arbitrary units, 42%, P < 0.05). No training effects were found for other NKA isoforms. Thus human skeletal muscle expresses all six NKA isoforms and not in a fiber-type-specific manner; this points to their different functional roles in skeletal muscle cells. Detection of elevated NKA β1 after RSE training demonstrates the sensitivity of the single-fiber Western blotting technique for fiber-type-specific intervention effects.

scholarly journals Effects of a brief high-fat diet and acute exercise on the mTORC1 and IKK/NF-κB pathways in rat skeletal muscle

2015 ◽  
Vol 40 (3) ◽  
pp. 251-262 ◽  
Author(s):  
Carlos M. Castorena ◽  
Edward B. Arias ◽  
Naveen Sharma ◽  
Gregory D. Cartee
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
High Fat Diet ◽  
Acute Exercise ◽  
Exercise Session ◽  
High Fat ◽  
Insulin Resistant ◽  
Mtorc1 Pathway ◽  
Exercise Induced

One exercise session can improve subsequent insulin-stimulated glucose uptake by skeletal muscle in healthy and insulin-resistant individuals. Our first aim was to determine whether a brief (2 weeks) high-fat diet (HFD) that caused muscle insulin resistance would activate the mammalian target of rapamycin complex 1 (mTORC1) and/or inhibitor of κB kinase/nuclear factor κB (IKK/NF-κB) pathways, which are potentially linked to induction of insulin resistance. Our second aim was to determine whether acute exercise that improved insulin-stimulated glucose uptake by muscles would attenuate activation of these pathways. We compared HFD-fed rats with rats fed a low-fat diet (LFD). Some animals from each diet group were sedentary and others were studied 3 h postexercise, when insulin-stimulated glucose uptake was increased. The results did not provide evidence that brief HFD activated either the mTORC1 (including phosphorylation of mTORSer2448, TSC2Ser939, p70S6KThr412, and RPS6Ser235/236) or the IKK/NF-κB (including abundance of IκBα or phosphorylation of NF-κBSer536, IKKα/βSer177/181, and IκBSer32) pathway in insulin-resistant muscles. Exercise did not oppose the activation of either pathway, as evidenced by no attenuation of phosphorylation of key proteins in the IKK/NF-κB pathway (NF-κBSer536, IKKα/βSer177/181, and IκBSer32), unaltered IκBα abundance, and no attenuation of phosphorylation of key proteins in the mTORC1 pathway (mTORSer2448, TSC2Ser939, and RPS6Ser235/236). Instead, exercise induced greater phosphorylation of 2 proteins of the mTORC1 pathway (PRAS40Thr246 and p70S6KThr412) in insulin-stimulated muscles, regardless of diet. Insulin resistance induced by a brief HFD was not attributable to greater activation of the mTORC1 or the IKK/NF-κB pathway in muscle, and exercise-induced improvement in insulin sensitivity was not attributable to attenuated activation of these pathways in muscle.

Gene Polymorphisms and Fiber-Type Composition of Human Skeletal Muscle

2012 ◽  
Vol 22 (4) ◽  
pp. 292-303 ◽  
Author(s):  
Ildus I. Ahmetov ◽  
Olga L. Vinogradova ◽  
Alun G. Williams
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Human Skeletal Muscle ◽  
Fiber Type ◽  
Vastus Lateralis Muscle ◽  
Type I ◽  
Fiber Types ◽  
Fiber Type Composition ◽  
Type Composition ◽  
Type I Fibers

The ability to perform aerobic or anaerobic exercise varies widely among individuals, partially depending on their muscle-fiber composition. Variability in the proportion of skeletal-muscle fiber types may also explain marked differences in aspects of certain chronic disease states including obesity, insulin resistance, and hypertension. In untrained individuals, the proportion of slow-twitch (Type I) fibers in the vastus lateralis muscle is typically around 50% (range 5–90%), and it is unusual for them to undergo conversion to fast-twitch fibers. It has been suggested that the genetic component for the observed variability in the proportion of Type I fibers in human muscles is on the order of 40–50%, indicating that muscle fiber-type composition is determined by both genotype and environment. This article briefly reviews current progress in the understanding of genetic determinism of fiber-type proportion in human skeletal muscle. Several polymorphisms of genes involved in the calcineurin–NFAT pathway, mitochondrial biogenesis, glucose and lipid metabolism, cytoskeletal function, hypoxia and angiogenesis, and circulatory homeostasis have been associated with fiber-type composition. As muscle is a major contributor to metabolism and physical strength and can readily adapt, it is not surprising that many of these gene variants have been associated with physical performance and athlete status, as well as metabolic and cardiovascular diseases. Genetic variants associated with fiber-type proportions have important implications for our understanding of muscle function in both health and disease.

Fiber type-specific determinants of V maxfor insulin-stimulated muscle glucose uptake in vivo

2003 ◽  
Vol 284 (3) ◽  
pp. E541-E548 ◽  
Author(s):  
Hilary Ann Petersen ◽  
Patrick T. Fueger ◽  
Deanna P. Bracy ◽  
David H. Wasserman ◽  
Amy E. Halseth
Keyword(s):  
Glucose Uptake ◽  
Fiber Type ◽  
Type I ◽  
Fiber Types ◽  
Maximal Velocity ◽  
Glucose Flux ◽  
Steady State Levels ◽  
Type I Fibers ◽  
Relationship Of

The aim of this study was to determine barriers limiting muscle glucose uptake (MGU) during increased glucose flux created by raising blood glucose in the presence of fixed insulin. The determinants of the maximal velocity ( V max) of MGU in muscles of different fiber types were defined. Conscious rats were studied during a 4 mU · kg−1 · min−1insulin clamp with plasma glucose at 2.5, 5.5, and 8.5 mM. [U-14C]mannitol and 3- O-methyl-[3H]glucose ([3H]MG) were infused to steady-state levels ( t = −180 to 0 min). These isotope infusions were continued from 0 to 40 min with the addition of a 2-deoxy-[3H]glucose ([3H]DG) infusion. Muscles were excised at t = 40 min. Glucose metabolic index (Rg) was calculated from muscle-phosphorylated [3H]DG. [U-14C]mannitol was used to determine extracellular (EC) H2O. Glucose at the outer ([G]om) and inner ([G]im) sarcolemmal surfaces was determined by the ratio of [3H]MG in intracellular to EC H2O and muscle glucose. Rg was comparable at the two higher glucose concentrations, suggesting that rates of uptake near V max were reached. In summary, by defining the relationship of arterial glucose to [G]om and [G]im in the presence of fixed hyperinsulinemia, it is concluded that 1) V max for MGU is limited by extracellular and intracellular barriers in type I fibers, as the sarcolemma is freely permeable to glucose; 2) V max is limited in muscles with predominantly type IIb fibers by extracellular resistance and transport resistance; and 3) limits to Rg are determined by resistance at multiple steps and are better defined by distributed control rather than by a single rate-limiting step.

scholarly journals Leptin administration improves skeletal muscle insulin responsiveness in diet-induced insulin-resistant rats

2001 ◽  
Vol 280 (1) ◽  
pp. E130-E142 ◽  
Author(s):  
Ben B. Yaspelkis ◽  
James R. Davis ◽  
Maziyar Saberi ◽  
Toby L. Smith ◽  
Reza Jazayeri ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Glucose Uptake ◽  
Whole Body ◽  
Glucose Disposal ◽  
High Fat ◽  
Insulin Resistant ◽  
Skeletal Muscle Glucose Uptake ◽  
Uptake And Transport

In addition to suppressing appetite, leptin may also modulate insulin secretion and action. Leptin was administered here to insulin-resistant rats to determine its effects on secretagogue-stimulated insulin release, whole body glucose disposal, and insulin-stimulated skeletal muscle glucose uptake and transport. Male Wistar rats were fed either a normal (Con) or a high-fat (HF) diet for 3 or 6 mo. HF rats were then treated with either vehicle (HF), leptin (HF-Lep, 10 mg · kg−1 · day−1 sc), or food restriction (HF-FR) for 12–15 days. Glucose tolerance and skeletal muscle glucose uptake and transport were significantly impaired in HF compared with Con. Whole body glucose tolerance and rates of insulin-stimulated skeletal muscle glucose uptake and transport in HF-Lep were similar to those of Con and greater than those of HF and HF-FR. The insulin secretory response to either glucose or tolbutamide (a pancreatic β-cell secretagogue) was not significantly diminished in HF-Lep. Total and plasma membrane skeletal muscle GLUT-4 protein concentrations were similar in Con and HF-Lep and greater than those in HF and HF-FR. The findings suggest that chronic leptin administration reversed a high-fat diet-induced insulin-resistant state, without compromising insulin secretion.

Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites

2006 ◽  
Vol 100 (5) ◽  
pp. 1467-1474 ◽  
Author(s):  
Jong Sam Lee ◽  
Srijan K. Pinnamaneni ◽  
Su Ju Eo ◽  
In Ho Cho ◽  
Jae Hwan Pyo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Polyunsaturated Fatty Acids ◽  
Glucose Uptake ◽  
High Fat ◽  
Insulin Resistant ◽  
L6 Myotubes ◽  
Lipid Metabolites

Consumption of a Western diet rich in saturated fats is associated with obesity and insulin resistance. In some insulin-resistant phenotypes this is associated with accumulation of skeletal muscle fatty acids. We examined the effects of diets high in saturated fatty acids (Sat) or n-6 polyunsaturated fatty acids (PUFA) on skeletal muscle fatty acid metabolite accumulation and whole-body insulin sensitivity. Male Sprague-Dawley rats were fed a chow diet (16% calories from fat, Con) or a diet high (53%) in Sat or PUFA for 8 wk. Insulin sensitivity was assessed by fasting plasma glucose and insulin and glucose tolerance via an oral glucose tolerance test. Muscle ceramide and diacylglycerol (DAG) levels and triacylglycerol (TAG) fatty acids were also measured. Both high-fat diets increased plasma free fatty acid levels by 30%. Compared with Con, Sat-fed rats were insulin resistant, whereas PUFA-treated rats showed improved insulin sensitivity. Sat caused a 125% increase in muscle DAG and a small increase in TAG. Although PUFA also resulted in a small increase in DAG, the excess fatty acids were primarily directed toward TAG storage (105% above Con). Ceramide content was unaffected by either high-fat diet. To examine the effects of fatty acids on cellular lipid storage and glucose uptake in vitro, rat L6 myotubes were incubated for 5 h with saturated and polyunsaturated fatty acids. After treatment of L6 myotubes with palmitate (C16:0), the ceramide and DAG content were increased by two- and fivefold, respectively, concomitant with reduced insulin-stimulated glucose uptake. In contrast, treatment of these cells with linoleate (C18:2) did not alter DAG, ceramide levels, and glucose uptake compared with controls (no added fatty acids). Both 16:0 and 18:2 treatments increased myotube TAG levels (C18:2 vs. C16:0, P < 0.05). These results indicate that increasing dietary Sat induces insulin resistance with concomitant increases in muscle DAG. Diets rich in n-6 PUFA appear to prevent insulin resistance by directing fat into TAG, rather than other lipid metabolites.

Exercise Effects on γ3-AMPK Activity, Akt Substrate of 160 kDa Phosphorylation, and Glucose Uptake in Muscle of Normal and Insulin Resistant Female Rats

2021 ◽  
Author(s):  
Haiyan Wang ◽  
Edward B. Arias ◽  
Jonas T. Treebak ◽  
Gregory D. Cartee
Keyword(s):  
Glucose Uptake ◽  
High Fat Diet ◽  
Skeletal Muscles ◽  
Acute Exercise ◽  
Female Rats ◽  
Male Rats ◽  
Signaling Proteins ◽  
Insulin Resistant ◽  
Low Fat Diet ◽  
Ampk Activity

Previous studies demonstrated that acute exercise can enhance glucose uptake (GU), γ3-AMPK activity, and Akt Substrate of 160 kDa (AS160) phosphorylation in skeletal muscles from low fat diet (LFD) and high fat diet (HFD) fed male rats. Because little is known about exercise-effects on these outcomes in females, we assessed postexercise GU by muscles incubated ±insulin, delta-insulin GU (GU of muscles incubated with insulin minus GU uptake of paired muscles incubated without insulin), and muscle signaling proteins from female rats fed a LFD or brief-HFD (2wk). Rats were sedentary (LFD-SED, HFD-SED) or swim-exercised. Immediately postexercise (IPEX) or 3h postexercise (3hPEX), epitrochlearis muscles were incubated (no insulin IPEX; ±insulin 3hPEX) to determine GU. Muscle γ3-AMPK activity (IPEX, 3hPEX) and phosphorylated AS160 (pAS160; 3hPEX) were also assessed. γ3-AMPK activity and insulin-independent GU of IPEX-rats exceeded sedentary-rats without diet-related differences in either outcome. At 3hPEX, both GU by insulin-stimulated muscles and delta-insulin GU exceeded their respective diet-matched sedentary controls. GU by insulin-stimulated muscles, but not delta-insulin GU for LFD-3hPEX exceeded HFD-3hPEX. LFD-3hPEX versus LFD-SED had greater γ3-AMPK activity and greater pAS160. HFD-3hPEX exceeded HFD-SED for pAS160, but not for γ3-AMPK activity. pAS160 and γ3-AMPK at 3hPEX did not differ between diet-groups. These results revealed that increased γ3-AMPK activity at 3hPEX was not essential for greater GU in insulin-stimulated muscle or greater delta-insulin GU in HFD-female rats. Similarly elevated γ3-AMPK activity in LFD-IPEX versus HFD-IPEX and pAS160 in LFD-3hPEX versus HFD-3hPEX may contribute to the comparable, delta-insulin GU at 3hPEX in both diet groups.

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