Muscle morphological and biochemical adaptations to training in obese Zucker rats

Torgan, C. E.; Brozinick, Joseph T.; Kastello, Gary M.; Ivy, J. L.

doi:10.1152/jappl.1989.67.5.1807

Cited by 38 publications

(29 citation statements)

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“…Moreover, a recent study has shown increases in several mitochondrial enzymes after 28 days of AICAR treatment (28). These and similar effects are well known as adaptive phenomena found in chronically exercising muscles (2,13,14,29) and support the idea that repetitive AMPK stimulation could be involved in mediating these long-term adaptive changes. However, the possible effect of long-term AICAR administration on insulin-stimulated glucose uptake is unsettled.…”

Section: Es Buhl and Associatessupporting

confidence: 83%

Chronic Treatment With 5-Aminoimidazole-4-Carboxamide-1- -D-Ribofuranoside Increases Insulin-Stimulated Glucose Uptake and GLUT4 Translocation in Rat Skeletal Muscles in a Fiber Type--Specific Manner

Buhl¹,

Jessen²,

Schmitz³

et al. 2001

Diabetes

167

146

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Recent studies have demonstrated that chronic administration of AICAR (5-aminoimidazole-4-carboxamide-1-␤-D-ribofuranoside), an activator of the AMP-activated protein kinase, increases hexokinase activity and the contents of total GLUT4 and glycogen in rat skeletal muscles. To explore whether AICAR also affects insulinstimulated glucose transport and GLUT4 cell surface content, Wistar rats were subcutaneously injected with AICAR for 5 days in succession (1 mg/g body wt). Maximally insulin-stimulated (60 nmol/l) glucose uptake was markedly increased in epitrochlearis (EPI) muscle (average 63%, P < 0.001, n = 18-19) and in extensor digitorum longus muscle (average 26%, P < 0.001, n = 26-30). In contrast, administration of AICAR did not maximally influence insulin-stimulated glucose transport in soleus muscle. Studies of EPI muscle with the 4,4Ј-O-[2-[2-[2-[2-[2-[6-(biotinylamino)hexanoyl]amino]ethoxy]ethoxy] ethoxy]-4-(1-azi-2,2,2,-trifluoroethyl)benzoyl]amino-1,3-propanediyl]bis-D-mannose photolabeling techniqueshowed a concomitant increase (average 68%, P < 0.02) in cell surface GLUT4 content after insulin exposure in AICARinjected rats when compared with controls. In conclusion, 5 days of AICAR administration induces a pronounced fiber type-specific increase in insulin-stimulated glucose uptake and GLUT4 cell surface content in rat skeletal muscle with the greatest effect observed on white fast-twitch glycolytic muscles (EPI). These results are comparable with the effects of chronic exercise training, and it brings the AMP-activated protein kinase into focus as a new interesting target for future pharmacological intervention in insulin-resistant conditions. Diabetes 50:12-17, 2001 P hysical exercise augments insulin sensitivity in skeletal muscle of insulin-resistant animals (1-4) and can also improve insulin sensitivity in type 2 diabetic individuals (5,6). Exercise is therefore pivotal in the treatment of type 2 diabetes. Studies in skeletal muscle from type 2 diabetic and (7) insulin-resistant prediabetic individuals (8) have shown an increased fraction of white type 2b muscle fibers. This change toward fast-twitch fibers in skeletal muscle has further been demonstrated in hyperinsulinemic rats (9) and in fructose-fed rats (an animal model of insulin-resistance) (10). Because it is well established that fasttwitch fibers (in particular type 2b fibers) are less insulin sensitive (11,12), this change in muscle morphology might potentially play a role in the decreased insulin action seen in skeletal muscle of insulin-resistant individuals.Muscle fibers also seem to differ in their ability to increase insulin action as a response to physical exercise (1-3). The exercise intensity used during exercise programs appears to play an important role for the fiber types recruited during the work performed and thus for their capability to exhibit adaptive changes with respect to insulin action (3) and oxidative capacity (13). Several animal studies featuring treadmill-running programs have shown that predominantly fast-t...

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Section: Es Buhl and Associatessupporting

confidence: 83%

Chronic Treatment With 5-Aminoimidazole-4-Carboxamide-1- -D-Ribofuranoside Increases Insulin-Stimulated Glucose Uptake and GLUT4 Translocation in Rat Skeletal Muscles in a Fiber Type--Specific Manner

Buhl¹,

Jessen²,

Schmitz³

et al. 2001

Diabetes

167

146

View full text Add to dashboard Cite

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“…34 ; r 2 ϭ 0.45, P Ͻ 0.05) and white (y ϭ 10.5x Ϫ0. 24 ; r 2 ϭ 0.34, P Ͻ 0.05) gastrocnemius muscles as well as total preperfusion triglyceride concentration (y ϭ 13.0x Ϫ0.36 ; r 2 ϭ 0.51, P Ͻ 0.05) (Fig. 4B) were exponential and found to be significant.…”

Section: Diabetes Vol 50 June 2001mentioning

confidence: 85%

“…The arterial-and venousspecific activities for palmitate did not vary over time and were not significantly different between the lean (52.9 Ϯ 6.8 and 50.1 Ϯ 6.1 Ci/mmol, respectively, P Ͼ 0.05) and obese (50.3 Ϯ 2.8 and 44.9 Ϯ 2.4 Ci/mmol, respectively, P Ͼ 0.05) rats. Total muscle triglyceride was calculated by estimating the contributions of red and white muscles to the perfused muscle mass (24). Statistical evaluation of the data was done using analysis of variance with Newman-Keul's test for post hoc multiple comparisons, when appropriate.…”

Section: Methodsmentioning

confidence: 99%

Increased Fatty Acid Uptake and Altered Fatty Acid Metabolism in Insulin-Resistant Muscle of Obese Zucker Rats

et al. 2001

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Altered muscle fatty acid (FA) metabolism may contribute to the presence of muscle insulin resistance in the genetically obese Zucker rat. To determine whether FA uptake and disposal are altered in insulin-resistant muscle, we measured palmitate uptake, oxidation, and incorporation into di-and triglycerides in isolated rat hindquarters, as well as muscle plasma membrane fatty acid-binding protein (FABP PM ) content of lean (n ‫؍‬ 16, fa/؉) and obese (n ‫؍‬ 15, fa/fa) Zucker rats (12 weeks of age). Hindquarters were perfused with 7 mmol/l glucose, 1,000 mol/l albumin-bound palmitate, and albumin-bound [1-14 C]palmitate at rest (no insulin). Glucose uptake was 42% lower in the obese than in the lean rats and indicated the presence of muscle insulin resistance. Fractional and total rates of palmitate uptake were 42 and 74% higher in the obese than in the lean rats and were associated with higher muscle FABP PM content (r 2 ‫؍‬ 0.69, P < 0.05). The percentage of palmitate oxidized was not significantly different between groups. FA disposal to storage was altered according to fiber type. When compared with lean rats, the rate of triglyceride synthesis in red muscle was 158% higher in obese rats, and the rate of palmitate incorporation into diglycerides in white muscle was 93% higher in obese rats. Pre-and postperfusion muscle triglyceride levels were higher in both red and white muscles of the obese rats. These results show that increased FA uptake and altered FA disposal to storage may contribute to the development of muscle insulin resistance in obese Zucker rats.

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“…The xanthine oxidase activity in muscle homogenates from obese Zucker rats tended to be reduced. This may be a reflection of a lower capillary density in the obese rats (32), although there is no consensus on this issue (33).…”

Section: Discussionmentioning

confidence: 99%

Insulin-Mediated Hemodynamic Changes Are Impaired in Muscle of Zucker Obese Rats

et al. 2002

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Insulin-mediated hemodynamic effects in muscle were assessed in relation to insulin resistance in obese and lean Zucker rats. Whole-body glucose infusion rate (GIR), femoral blood flow (FBF), hindleg glucose extraction (HGE), hindleg glucose uptake (HGU), 2-deoxyglucose (DG) uptake into muscles of the lower leg (R g ), and metabolism of infused 1-methylxanthine (1-MX) to measure capillary recruitment were determined for isogylcemic (4.8 ؎ 0.2 mmol/l, lean; 11.7 ؎ 0.6 mmol/l, obese) insulin-clamped (20 mU ⅐ min ؊1 ⅐ kg ؊1 ؋ 2 h) and saline-infused control anesthetized agematched (20 weeks) lean and obese animals. Obese rats (445 ؎ 5 g) were less responsive to insulin than lean animals (322 ؎ 4 g) for GIR (7.7 ؎ 1.4 vs. 22.2 ؎ 1.1 mg ⅐ min ؊1 ⅐ kg ؊1 , respectively), and when compared with saline-infused controls there was no increase due to insulin by obese rats in FBF, HGE, HGU, and R g of soleus, plantaris, red gastrocnemius, white gastrocnemius, extensor digitorum longus (EDL), or tibialis muscles. In contrast, lean animals showed marked increases due to insulin in FBF (5.3-fold), HGE (5-fold), HGU (8-fold), and R g (ϳ5.6-fold). Basal (saline) hindleg 1-MX metabolism was 1.5-fold higher in lean than in obese Zucker rats, and insulin increased in only that of the lean. Hindleg 1-MX metabolism in the obese decreased slightly in response to insulin, thus postinsulin lean was 2.6-fold that of the postinsulin obese. We conclude that muscle insulin resistance of obese Zucker rats is accompanied by impaired hemodynamic responses to insulin, including capillary recruitment and FBF. Diabetes 51:3492-3498, 2002

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Muscle morphological and biochemical adaptations to training in obese Zucker rats

Cited by 38 publications

References 0 publications

Chronic Treatment With 5-Aminoimidazole-4-Carboxamide-1- -D-Ribofuranoside Increases Insulin-Stimulated Glucose Uptake and GLUT4 Translocation in Rat Skeletal Muscles in a Fiber Type--Specific Manner

Chronic Treatment With 5-Aminoimidazole-4-Carboxamide-1- -D-Ribofuranoside Increases Insulin-Stimulated Glucose Uptake and GLUT4 Translocation in Rat Skeletal Muscles in a Fiber Type--Specific Manner

Increased Fatty Acid Uptake and Altered Fatty Acid Metabolism in Insulin-Resistant Muscle of Obese Zucker Rats

Insulin-Mediated Hemodynamic Changes Are Impaired in Muscle of Zucker Obese Rats

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