scholarly journals Abnormalities in the Fiber Composition and Capillary Architecture in the Soleus Muscle of Type 2 Diabetic Goto-Kakizaki Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Shinichiro Murakami ◽  
Naoto Fujita ◽  
Hiroyo Kondo ◽  
Isao Takeda ◽  
Ryusuke Momota ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Fiber Type ◽  
Type I ◽  
Gk Rats ◽  
Type Transformation ◽  
3D Architecture ◽  
Type 2 Diabetic

Type 2 diabetes mellitus is linked to impaired skeletal muscle glucose uptake and storage. This study aimed to investigate the fiber type distributions and the three-dimensional (3D) architecture of the capillary network in the skeletal muscles of type 2 diabetic rats. Muscle fiber type transformation, succinate dehydrogenase (SDH) activity, capillary density, and 3D architecture of the capillary network in the soleus muscle were determined in 36-week-old Goto-Kakizaki (GK) rats as an animal model of nonobese type 2 diabetes and age-matched Wistar (Cont) rats. Although the soleus muscle of Cont rats comprised both type I and type IIA fibers, the soleus muscle of GK rats had only type I fibers. In addition, total SDH activity in the soleus muscle of GK rats was significantly lower than that in Cont rats because GK rats had no high-SDH activity type IIA fiber in the soleus muscle. Furthermore, the capillary diameter, capillary tortuosity, and microvessel volume in GK rats were significantly lower than those in Cont rats. These results indicate that non-obese diabetic GK rats have muscle fiber type transformation, low SDH activity, and reduced skeletal muscle capillary content, which may be related to the impaired glucose metabolism characteristic of type 2 diabetes.

Skeletal muscle capillary density and microvascular function are compromised with aging and type 2 diabetes

2014 ◽  
Vol 116 (8) ◽  
pp. 998-1005 ◽  
Author(s):  
Bart B. L. Groen ◽  
Henrike M. Hamer ◽  
Tim Snijders ◽  
Janneau van Kranenburg ◽  
Dionne Frijns ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Fiber Type ◽  
Capillary Density ◽  
Boundary Region ◽  
Whole Body ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

Adequate muscle perfusion is required for the maintenance of skeletal muscle mass. Impairments in microvascular structure and/or function with aging and type 2 diabetes have been associated with the progressive loss of skeletal muscle mass. Our objective was to compare muscle fiber type specific capillary density and endothelial function between healthy young men, healthy older men, and age-matched type 2 diabetes patients. Fifteen healthy young men (24 ± 1 yr), 15 healthy older men (70 ± 2 yr), and 15 age-matched type 2 diabetes patients (70 ± 1 yr) were selected to participate in the present study. Whole body insulin sensitivity, muscle fiber type specific capillary density, sublingual microvascular density, and dimension of the erythrocyte-perfused boundary region were assessed to evaluate the impact of aging and/or type 2 diabetes on microvascular structure and function. Whole body insulin sensitivity was significantly lower at a more advanced age, with lowest values reported in the type 2 diabetic patients. In line, skeletal muscle capillary contacts were much lower in the older and older type 2 diabetic patients when compared with the young. Sidestream darkfield imaging showed a significantly greater thickness of the erythrocyte perfused boundary region in the type 2 diabetic patients compared with the young. Skeletal muscle capillary density is reduced with aging and type 2 diabetes and accompanied by impairments in endothelial glycocalyx function, which is indicative of compromised vascular function.

scholarly journals Type 2 diabetes mellitus in the Goto-Kakizaki rat impairs microvascular function and contributes to premature skeletal muscle fatigue

2019 ◽  
Vol 126 (3) ◽  
pp. 626-637 ◽  
Author(s):  
Jefferson C. Frisbee ◽  
Matthew T. Lewis ◽  
Jonathan D. Kasper ◽  
Paul D. Chantler ◽  
Robert W. Wiseman
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Structure Function ◽  
Vascular Structure ◽  
Gk Rats ◽  
The Impact

Despite extensive investigation into the impact of metabolic disease on vascular function and, by extension, tissue perfusion and organ function, interpreting results for specific risk factors can be complicated by the additional risks present in most models. To specifically determine the impact of type 2 diabetes without obesity on skeletal muscle microvascular structure/function and on active hyperemia with elevated metabolic demand, we used 17-wk-old Goto-Kakizaki (GK) rats to study microvascular function at multiple levels of resolution. Gracilis muscle arterioles demonstrated blunted dilation to acetylcholine (both ex vivo proximal and in situ distal arterioles) and elevated shear (distal arterioles only). All other alterations to reactivity appeared to reflect compromised endothelial function associated with increased thromboxane (Tx)A2 production and oxidant stress/inflammation rather than alterations to vascular smooth muscle function. Structural changes to the microcirculation of GK rats were confined to reduced microvessel density of ~12%, with no evidence for altered vascular wall mechanics. Active hyperemia with either field stimulation of in situ cremaster muscle or electrical stimulation via the sciatic nerve for in situ gastrocnemius muscle was blunted in GK rats, primarily because of blunted functional dilation of skeletal muscle arterioles. The blunted active hyperemia was associated with impaired oxygen uptake (V̇o2) across the muscle and accelerated muscle fatigue. Acute interventions to reduce oxidant stress (TEMPOL) and TxA2 action (SQ-29548) or production (dazmegrel) improved muscle perfusion, V̇o2, and muscle performance. These results suggest that type 2 diabetes mellitus in GK rats impairs skeletal muscle arteriolar function apparently early in the progression of the disease and potentially via an increased reactive oxygen species/inflammation-induced TxA2 production/action on network function as a major contributing mechanism. NEW & NOTEWORTHY The impact of type 2 diabetes mellitus on vascular structure/function remains an area lacking clarity. Using diabetic Goto-Kakizaki rats before the development of other risk factors, we determined alterations to vascular structure/function and skeletal muscle active hyperemia. Type 2 diabetes mellitus reduced arteriolar endothelium-dependent dilation associated with increased thromboxane A2 generation. Although modest microvascular rarefaction was evident, there were no other alterations to vascular structure/function. Skeletal muscle active hyperemia was blunted, although it improved after antioxidant or anti-thromboxane A2 treatment.

scholarly journals Dysfunction of muscle contraction with impaired intracellular Ca2+ handling in skeletal muscle and the effect of exercise training in male db/db mice

2019 ◽  
Vol 126 (1) ◽  
pp. 170-182 ◽  
Author(s):  
Hiroaki Eshima ◽  
Yoshifumi Tamura ◽  
Saori Kakehi ◽  
Kyoko Nakamura ◽  
Nagomi Kurebayashi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Muscle Contraction ◽  
Contractile Function ◽  
Contractile Force ◽  
Contractile Dysfunction ◽  
Muscle Contractile ◽  
Type 2 Diabetic

Type 2 diabetes is characterized by reduced contractile force production and increased fatigability of skeletal muscle. While the maintenance of Ca2+ homeostasis during muscle contraction is a requisite for optimal contractile function, the mechanisms underlying muscle contractile dysfunction in type 2 diabetes are unclear. Here, we investigated skeletal muscle contractile force and Ca2+ flux during contraction and pharmacological stimulation in type 2 diabetic model mice ( db/db mice). Furthermore, we investigated the effect of treadmill exercise training on muscle contractile function. In male db/db mice, muscle contractile force and peak Ca2+ levels were both lower during tetanic stimulation of the fast-twitch muscles, while Ca2+ accumulation was higher after stimulation compared with control mice. While 6 wk of exercise training did not improve glucose tolerance, exercise did improve muscle contractile dysfunction, peak Ca2+ levels, and Ca2+ accumulation following stimulation in male db/db mice. These data suggest that dysfunctional Ca2+ flux may contribute to skeletal muscle contractile dysfunction in type 2 diabetes and that exercise training may be a promising therapeutic approach for dysfunctional skeletal muscle contraction. NEW & NOTEWORTHY The purpose of this study was to examine muscle contractile function and Ca2+ regulation as well as the effect of exercise training in skeletal muscle in obese diabetic mice ( db/db). We observed impairment of muscle contractile force and Ca2+ regulation in a male type 2 diabetic animal model. These dysfunctions in muscle were improved by 6 wk of exercise training.

Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading

1999 ◽  
Vol 277 (2) ◽  
pp. R601-R606 ◽  
Author(s):  
Christian J. Carlson ◽  
Frank W. Booth ◽  
Scott E. Gordon
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Soleus Muscle ◽  
Fiber Type ◽  
Weight Bearing ◽  
Mrna Abundance ◽  
Hindlimb Unloading ◽  
Negative Regulator ◽  
Type I ◽  
Mrna Levels

Transgenic mice lacking a functional myostatin (MSTN) gene demonstrate greater skeletal muscle mass resulting from muscle fiber hypertrophy and hyperplasia (McPherron, A. C., A. M. Lawler, and S.-J. Lee. Nature 387: 83–90, 1997). Therefore, we hypothesized that, in normal mice, MSTN may act as a negative regulator of muscle mass. Specifically, we hypothesized that the predominately slow (type I) soleus muscle, which demonstrates greater atrophy than the fast (type II) gastrocnemius-plantaris complex (Gast/PLT), would show more elevation in MSTN mRNA abundance during hindlimb unloading (HU). Surprisingly, MSTN mRNA was not detectable in weight-bearing or HU soleus muscle, which atrophied 42% by the 7th day of HU in female ICR mice. In contrast, MSTN mRNA was present in weight-bearing Gast/PLT muscle and was significantly elevated (67%) at 1 day but not at 3 or 7 days of HU. However, the Gast/PLT muscle had only atrophied 17% by the 7th day of HU. Because the soleus is composed only of type I and IIa fibers, whereas the Gast/PLT expresses type IId/x and IIb in addition to type I and IIa, it was necessary to perform a more careful analysis of the relationship between MSTN mRNA levels and myosin heavy-chain (MHC) isoform expression (as a marker of fiber type). A significant correlation ( r = 0.725, P < 0.0005) was noted between the percentage of MHC isoform IIb expression and MSTN mRNA abundance in several muscles of the mouse hindlimb. These results indicate that MSTN expression is not strongly associated with muscle atrophy induced by HU; however, it is strongly associated with MHC isoform IIb expression in normal muscle.

scholarly journals Plasma FFA utilization and fatty acid-binding protein content are diminished in type 2 diabetic muscle

2000 ◽  
Vol 279 (1) ◽  
pp. E146-E154 ◽  
Author(s):  
Ellen E. Blaak ◽  
Anton J. M. Wagenmakers ◽  
Jan F. C. Glatz ◽  
Bruce H. R. Wolffenbuttel ◽  
Gerrit J. Kemerink ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Fasted State ◽  
Plasma Ffa ◽  
Type 2 Diabetic

In this study, we investigated the hypothesis that impairments in forearm skeletal muscle free fatty acid (FFA) metabolism are present in patients with type 2 diabetes both in the overnight fasted state and during β-adrenergic stimulation. Eight obese subjects with type 2 diabetes and eight nonobese controls (Con) were studied using the forearm balance technique and indirect calorimetry during infusion of the stable isotope tracer [U-13C]palmitate after an overnight fast and during infusion of the nonselective β-agonist isoprenaline (Iso, 20 ng · kg lean body mass−1 · min−1). Additionally, activities of mitochondrial enzymes and of cytoplasmatic fatty acid-binding protein (FABP) were determined in biopsies from the vastus lateralis muscle. Both during fasting and Iso infusion, the tracer balance data showed that forearm muscle FFA uptake (Con vs. type 2: fast 449 ± 69 vs. 258 ± 42 and Iso 715 ± 129 vs. 398 ± 70 nmol · 100 ml tissue−1 · min−1, P < 0.05) and FFA release were lower in type 2 diabetes compared with Con. Also, the oxidation of plasma FFA by skeletal muscle was blunted during Iso infusion in type 2 diabetes (Con vs. type 2: Iso 446 ± 274 vs. 16 ± 70 nmol · 100 ml tissue−1 · min−1, P < 0.05). The net forearm glycerol release was increased in type 2 diabetic subjects ( P < 0.05), which points to an increased forearm lipolysis. Additionally, skeletal muscle cytoplasmatic FABP content and the activity of muscle oxidative enzymes were lowered in type 2 diabetes. We conclude that the uptake and oxidation of plasma FFA are impaired in the forearm muscles of type 2 diabetic subjects in the overnight fasted state with and without Iso stimulation.

scholarly journals Prolonged exercise training increases intramuscular lipid content and perilipin 2 expression in type I muscle fibers of patients with type 2 diabetes

2012 ◽  
Vol 303 (9) ◽  
pp. E1158-E1165 ◽  
Author(s):  
C. S. Shaw ◽  
S. O. Shepherd ◽  
A. J. M. Wagenmakers ◽  
D. Hansen ◽  
P. Dendale ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Exercise Training ◽  
Fiber Type ◽  
Muscle Fibers ◽  
Whole Body ◽  
Type I ◽  
Type Ii ◽  
Perilipin 2 ◽  
Diabetes Patients

The aim of the present study was to investigate changes in intramuscular triglyceride (IMTG) content and perilipin 2 expression in skeletal muscle tissue following 6 mo of endurance-type exercise training in type 2 diabetes patients. Ten obese male type 2 diabetes patients (age 62 ± 1 yr, body mass index BMI 31 ± 1 kg/m2) completed three exercise sessions/week consisting of 40 min of continuous endurance-type exercise at 75% V̇o2 peak for a period of 6 mo. Muscle biopsies collected at baseline and after 2 and 6 mo of intervention were analyzed for IMTG content and perilipin 2 expression using fiber type-specific immunofluorescence microscopy. Endurance-type exercise training reduced trunk body fat by 6 ± 2% and increased whole body oxygen uptake capacity by 13 ± 7% ( P < 0.05). IMTG content increased twofold in response to the 6 mo of exercise training in both type I and type II muscle fibers ( P < 0.05). A threefold increase in perilipin 2 expression was observed from baseline to 2 and 6 mo of intervention in the type I muscle fibers only (1.1 ± 0.3, 3.4 ± 0.6, and 3.6 ± 0.6% of fibers stained, respectively, P < 0.05). Exercise training induced a 1.6-fold increase in mitochondrial content after 6 mo of training in both type I and type II muscle fibers ( P < 0.05). In conclusion, this is the first study to report that prolonged endurance-type exercise training increases the expression of perilipin 2 alongside increases in IMTG content in a type I muscle fiber-type specific manner in type 2 diabetes patients.

scholarly journals Gymnemic acid, a potent antidiabetic agent protects skeletal muscle from hyperglycemia mediated oxidative stress and apoptotic events in High fat and High fructose diet fed adult rats

2020 ◽  
Vol 11 (2) ◽  
pp. 1526-1538
Author(s):  
Porkodi Karthikeyan ◽  
Lakshmi Narasimhan Chakrapani ◽  
Thangarajeswari Mohan ◽  
Bhavani Tamilarasan ◽  
Pughazhendi Kannan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Diabetic Rats ◽  
High Fat ◽  
Gymnemic Acid ◽  
High Fructose ◽  
Type 2 Diabetic

Type 2 diabetes is delineated by impaired metabolic flexibility, and intramyocellular lipid accumulation, causing insulin resistance, particularly in skeletal muscle by reducing insulin-stimulated glucose uptake. High-fat diet and high fructose (HFD and HF) administration in rodents bestows a model for hyperlipidemia, insulin resistance, and Type 2 diabetes. The current study is focused on elucidating the role of Gymnemic acid in combating hyperglycemia mediated oxidative stress and apoptotic events in the skeletal muscle of HFD and HF induced Type 2 diabetes in Wistar albino rats by boosting antioxidant defense system. Gymnemic acid, a saponin of triterpene glycoside contained in leaves of Gymnema Sylvestre, has potent anti-diabetic properties. Treatment with Gymnemic acid restored the antioxidant status (Gpx, SOD, CAT, GR, Vit C & Vit E) with significant (p<0.05) decrease in free radical levels and reinvigorated the expression of apoptotic and antiapoptotic proteins in Type 2 diabetic rats. Histopathological data demonstrate that oral administration of Gymnemic acid protects skeletal muscle fibers from an oxidative niche in HFD and HF in Type 2 diabetic rats. In accordance with this, Gymnemic acid might be regarded as a promising therapeutic agent against Type 2 diabetes, thereby restoring skeletal muscle integrity and function.

scholarly journals Effects of raising muscle glycogen synthesis rate on skeletal muscle ATP turnover rate in type 2 diabetes

2011 ◽  
Vol 301 (6) ◽  
pp. E1155-E1162 ◽  
Author(s):  
Ee L. Lim ◽  
Kieren G. Hollingsworth ◽  
Fiona E. Smith ◽  
Peter E. Thelwall ◽  
Roy Taylor
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Glycogen ◽  
Glycogen Synthesis ◽  
Turnover Rates ◽  
Atp Turnover ◽  
Muscle Glycogen Synthesis ◽  
Type 2 Diabetic

Mitochondrial dysfunction has been implicated in the pathogenesis of type 2 diabetes. We hypothesized that any impairment in insulin-stimulated muscle ATP production could merely reflect the lower rates of muscle glucose uptake and glycogen synthesis, rather than cause it. If this is correct, muscle ATP turnover rates in type 2 diabetes could be increased if glycogen synthesis rates were normalized by the mass-action effect of hyperglycemia. Isoglycemic- and hyperglycemic-hyperinsulinemic clamps were performed on type 2 diabetic subjects and matched controls, with muscle ATP turnover and glycogen synthesis rates measured using 31P- and 13C-magnetic resonance spectroscopy, respectively. In diabetic subjects, hyperglycemia increased muscle glycogen synthesis rates to the level observed in controls at isoglycemia [from 19 ± 9 to 41 ± 12 μmol·l−1·min−1 ( P = 0.012) vs. 40 ± 7 μmol·l−1·min−1 in controls]. This was accompanied by a modest increase in muscle ATP turnover rates (7.1 ± 0.5 vs. 8.6 ± 0.7 μmol·l−1·min−1, P = 0.04). In controls, hyperglycemia brought about a 2.5-fold increase in glycogen synthesis rates (100 ± 24 vs. 40 ± 7 μmol·l−1·min−1, P = 0.028) and a 23% increase in ATP turnover rates (8.1 ± 0.9 vs. 10.0 ± 0.9 μmol·l−1·min−1, P = 0.025) from basal state. Muscle ATP turnover rates correlated positively with glycogen synthesis rates ( rs = 0.46, P = 0.005). Changing the rate of muscle glucose metabolism in type 2 diabetic subjects alters demand for ATP synthesis at rest. In type 2 diabetes, skeletal muscle ATP turnover rates reflect the rate of glucose uptake and glycogen synthesis, rather than any primary mitochondrial defect.

Thiazolidinediones upregulate impaired fatty acid uptake in skeletal muscle of type 2 diabetic subjects

2003 ◽  
Vol 285 (2) ◽  
pp. E354-E362 ◽  
Author(s):  
Hubertina M. Wilmsen ◽  
Theodore P. Ciaraldi ◽  
Leslie Carter ◽  
Nabeela Reehman ◽  
Sunder R. Mudaliar ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Acid Uptake ◽  
Cd36 Expression ◽  
Palmitate Uptake ◽  
Type 2 Diabetic

We examined the regulation of free fatty acid (FFA, palmitate) uptake into skeletal muscle cells of nondiabetic and type 2 diabetic subjects. Palmitate uptake included a protein-mediated component that was inhibited by phloretin. The protein-mediated component of uptake in muscle cells from type 2 diabetic subjects (78 ± 13 nmol · mg protein-1 · min-1) was reduced compared with that in nondiabetic muscle (150 ± 17, P < 0.01). Acute insulin exposure caused a modest (16 ± 5%, P < 0.025) but significant increase in protein-mediated uptake in nondiabetic muscle. There was no significant insulin effect in diabetic muscle (+19 ± 19%, P = not significant). Chronic (4 day) treatment with a series of thiazolidinediones, troglitazone (Tgz), rosiglitazone (Rgz), and pioglitazone (Pio) increased FFA uptake. Only the phloretin-inhibitable component was increased by treatment, which normalized this activity in diabetic muscle cells. Under the same conditions, FFA oxidation was also increased by thiazolidinedione treatment. Increases in FFA uptake and oxidation were associated with upregulation of fatty acid translocase (FAT/CD36) expression. FAT/CD36 protein was increased by Tgz (90 ± 22% over control), Rgz (146 ± 42%), and Pio (111 ± 37%, P < 0.05 for all 3) treatment. Tgz treatment had no effect on fatty acid transporter protein-1 and membrane-associated plasmalemmal fatty acid-binding protein mRNA expression. We conclude that FFA uptake into cultured muscle cells is, in part, protein mediated and acutely insulin responsive. The basal activity of FFA uptake is impaired in type 2 diabetes. In addition, chronic thiazolidinedione treatment increased FFA uptake and oxidation into cultured human skeletal muscle cells in concert with upregulation of FAT/CD36 expression. Increased FFA uptake and oxidation may contribute to lower circulating FFA levels and reduced insulin resistance in skeletal muscle of individuals with type 2 diabetes following thiazolidinedione treatment.

Carnitine delays rat skeletal muscle fatigue in vitro

1993 ◽  
Vol 75 (4) ◽  
pp. 1595-1600 ◽  
Author(s):  
E. P. Brass ◽  
A. M. Scarrow ◽  
L. J. Ruff ◽  
K. A. Masterson ◽  
E. Van Lunteren
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Fiber Type ◽  
Type I ◽  
Glycogen Depletion ◽  
Rat Skeletal Muscle ◽  
Skeletal Muscle Function ◽  
Total Carnitine ◽  
Initial Force

Carnitine has been used to enhance human exercise performance. To test the hypothesis that carnitine can directly modify skeletal muscle function, fatigue of isolated rat skeletal muscle strips was studied in vitro. Carnitine (10 mM) did not modify the initial force of soleus contraction. The time over which force declined by 50% during repetitive electrical stimulation of the soleus muscle (fiber type I) was prolonged 25% in the presence of 10 mM carnitine. In contrast, carnitine had no effect on the fatigue of extensor digitorum longus muscle strips (fiber type II). The beneficial effect of carnitine on soleus muscle strips was not observed if the routine 30-min preincubation in the presence of carnitine was decreased to 5 min; it was associated with a five- to sixfold increase in muscle total carnitine content and a 50#x2013;150% increase in muscle long-chain acylcarnitine content. Carnitine did not consistently modify lactate accumulation or glycogen depletion during the fatigue protocol. Incubation with propionyl-L-carnitine resulted in a decreased initial force of contraction and a delay in reaching maximal contractile force. Thus, carnitine can directly improve the fatigue characteristics of muscles enriched in type I fibers.

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