Immunization against IGF-I prevents increases in protein synthesis in diabetic rats after resistance exercise

2001 ◽  
Vol 280 (6) ◽  
pp. E877-E885 ◽  
Author(s):  
Mark J. Fedele ◽  
Charles H. Lang ◽  
Peter A. Farrell
Keyword(s):  
Protein Synthesis ◽  
Resistance Exercise ◽  
Passive Immunization ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Factor I ◽  
Sedentary Group ◽  
Sprague Dawley Rats ◽  
Igf I ◽  
Exercise Induced

These studies examined whether passive immunization against insulin-like growth factor I (IGF-I) would prevent increases in rates of protein synthesis in skeletal muscle of diabetic rats after resistance exercise. Male Sprague-Dawley rats were pancreatectomized and randomly assigned to either an exercise or a sedentary group. Animals in each of these groups received either an IGF-I antibody or a nonspecific IgG from a subcutaneous osmotic pump. Exercise did not change plasma or gastrocnemius IGF-I concentrations in nondiabetic rats. However, plasma and muscle IGF-I concentrations were higher in IgG-treated diabetic rats that exercised compared with respective sedentary groups ( P < 0.05). Passively immunized diabetic rats did not exhibit the same exercise-induced increase in IGF-I concentrations. In nondiabetic rats, protein synthesis rates were higher after exercise in both control and immunized groups. In diabetic rats, exercise increased protein synthesis in the IgG-treated animals but not in those treated with IGF-I antibody. There was also a significant positive correlation between both plasma and gastrocnemius IGF-I concentrations and rates of protein synthesis in diabetic ( P < 0.01), but not nondiabetic, rats. These results suggest that IGF-I is compensatory for insulin in hypoinsulinemic rats by facilitating an anabolic response after acute resistance exercise.

Selected Contribution: IGF-I antibody prevents increases in protein synthesis in epitrochlearis muscles from refed, diabetic rats

2001 ◽  
Vol 90 (3) ◽  
pp. 1166-1173 ◽  
Author(s):  
Mark J. Fedele ◽  
Thomas C. Vary ◽  
Peter A Farrell
Keyword(s):  
Protein Synthesis ◽  
Growth Factor ◽  
Protein Degradation ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Anabolic Response ◽  
Partial Pancreatectomy ◽  
Factor I ◽  
Sprague Dawley Rats ◽  
Igf I

The purpose of this study was to examine whether immune neutralization of muscle-produced insulin-like growth factor I (IGF-I) would prevent an appropriate anabolic response to refeeding in diabetic rats. Male Sprague-Dawley rats were made diabetic by partial pancreatectomy and were randomly assigned to be either control-fed, fasted, or fasted-refed ( n = 7–8 per group). Diabetes decreased rates of protein synthesis and increased rates of protein degradation in incubated epitrochlearis muscles ( P < 0.05). In both groups of rats, fasting lowered protein synthesis and increased proteolysis and subsequent refeeding returned both parameters to near basal values ( P < 0.05). Neutralization of muscle IGF-I by the addition of IGF-I antibody to the incubation medium reduced protein synthesis an average of 22% for all groups ( P < 0.05). However, rates of protein degradation were not affected. In nondiabetic rats, refeeding increased protein synthesis in both control and antibody-treated muscles ( P < 0.05). Refeeding also increased protein synthesis in the control muscles from diabetic rats ( P < 0.01). In contrast, muscles from diabetic rats that were incubated with anti-IGF-I did not increase protein synthesis in response to refeeding. These data suggest that immune neutralization of muscle IGF-I in hypoinsulinemic rats negated the ability of endogenous IGF-I to promote protein synthesis and thereby prevented an appropriate anabolic response.

Regulation of protein synthesis after acute resistance exercise in diabetic rats

1999 ◽  
Vol 276 (4) ◽  
pp. E721-E727 ◽  
Author(s):  
Peter A. Farrell ◽  
Mark J. Fedele ◽  
Thomas C. Vary ◽  
Scot R. Kimball ◽  
Charles H. Lang ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Resistance Exercise ◽  
Diabetic Rats ◽  
Initiation Factor ◽  
Moderate Intensity ◽  
Sprague Dawley ◽  
Partial Pancreatectomy ◽  
Igf I ◽  
Arterial Plasma

These studies determined whether insulin-like growth factor-I (IGF-I) involvement in exercise-stimulated anabolic processes becomes more evident during hypoinsulinemia. Male Sprague-Dawley rats ( n = 6–12/group) were made diabetic (blood glucose ≅ 300 mg/dl) by partial pancreatectomy (PPX) or remained nondiabetic (glucose ≅ 144 mg/dl). Rats performed acute resistance exercise by repetitive standing on the hindlimbs with weighted backpacks (ex), or they remained sedentary (sed). Resistance exercise caused increases in rates of protein synthesis (nmol Phe incorporated ⋅ g muscle−1 ⋅ h−1, measured for gastrocnemius muscle in vivo 16 h after exercise) for both nondiabetic [sed = 154 ± 6 (SE) vs. ex = 189 ± 7] and diabetic rats (PPXsed = 152 ± 11 vs. PPXex = 202 ± 14, P < 0.05). Arterial plasma insulin concentrations in diabetic rats, ≅180 pM, were less than one-half those found in nondiabetic rats, ≅444 pM, ( P < 0.05). The activity of eukaryotic initiation factor 2B (eIF2B; pmol GDP exchanged/min) was higher ( P < 0.05) in ex rats (sed = 0.028 ± 0.006 vs. ex = 0.053 ± 0.015; PPXsed = 0.033 ± 0.013 vs. PPXex = 0.047 ± 0.009) regardless of diabetic status. Plasma IGF-I concentrations were higher in ex compared with sed diabetic rats ( P < 0.05). In contrast, plasma IGF-I was not different in nondiabetic ex or sed rats. Muscle IGF-I (ng/g wet wt) was similar in ex and sed nondiabetic rats, but in diabetic rats was 2- to 3-fold higher in ex ( P < 0.05) than in sed rats. In conclusion, moderate hypoinsulinemia that is sufficient to alter glucose homeostasis does not inhibit an increase in rates of protein synthesis after acute moderate-intensity resistance exercise. This preserved response may be due to a compensatory increase in muscle IGF-I content and a maintained ability to activate eIF2B.

Severe diabetes inhibits resistance exercise-induced increase in eukaryotic initiation factor 2B activity

2001 ◽  
Vol 91 (1) ◽  
pp. 79-84 ◽  
Author(s):  
John C. Kostyak ◽  
Scot R. Kimball ◽  
Leonard S. Jefferson ◽  
Peter A. Farrell
Keyword(s):  
Protein Synthesis ◽  
Resistance Exercise ◽  
Diabetic Rats ◽  
Initiation Factor ◽  
Moderate Intensity ◽  
Eukaryotic Initiation Factor ◽  
Sprague Dawley ◽  
Partial Pancreatectomy ◽  
Severe Diabetes ◽  
Exercise Induced

Rates of protein synthesis are reduced in severely diabetic rats. A potential mechanism through which insulin can stimulate protein synthesis is modulation of the activity of eukaryotic initiation factor 2B (eIF2B). The activity of this factor is elevated after exercise in nondiabetic rats but is markedly lower in skeletal muscle from nonexercised severely diabetic rats. We tested the hypothesis that a failure to increase eIF2B activity after exercise is one potential reason for a failure of severely diabetic rats to increase rates of protein synthesis after resistance exercise. Diabetic (partial pancreatectomy, plasma glucose >475 mg/dl) and nondiabetic male Sprague-Dawley rats (∼300 g) performed acute moderate-intensity resistance exercise or remained sedentary. Rates of protein synthesis were higher in nondiabetic rats and increased significantly with exercise, while no elevation was found in severely diabetic rats. The activity of eIF2B was higher ( P < 0.05) in exercised nondiabetic than in sedentary nondiabetic rats (0.096 ± 0.016 and 0.064 ± 0.02 pmol GDP exchanged/min, respectively), but no difference was observed between sedentary and exercised diabetic rats (0.037 ± 0.001 and 0.044 ± 0.008 pmol GDP exchanged/min, respectively), and these activities were lower ( P < 0.05) than in nondiabetic animals. These data suggest that severe hypoinsulinemia is associated with an inability to increase eIF2B activity in response to exercise.

scholarly journals Eukaryotic initiation factors and protein synthesis after resistance exercise in rats

2000 ◽  
Vol 88 (3) ◽  
pp. 1036-1042 ◽  
Author(s):  
Peter A. Farrell ◽  
Jazmir M. Hernandez ◽  
Mark J. Fedele ◽  
Thomas C. Vary ◽  
Scot R. Kimball ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Resistance Exercise ◽  
Translational Control ◽  
Sprague Dawley ◽  
Initiation Factors ◽  
Eukaryotic Initiation Factors ◽  
Sprague Dawley Rats ◽  
Arterial Plasma ◽  
Response To Exercise

Translational control of protein synthesis depends on numerous eukaryotic initiation factors (eIFs) and we have previously shown ( Am. J. Physiol. Endocrinol. Metab. 276: E721–E727, 1999) that increases in one factor, eIF2B, are associated with increases in rates of protein synthesis after resistance exercise in rats. In the present study we investigated whether the eIF4E family of initiation factors is also involved with an anabolic response to exercise. Male Sprague-Dawley rats either remained sedentary ( n = 6) or performed acute resistance exercise ( n = 6), and rates of protein synthesis were assessed in vivo 16 h after the last session of resistance exercise. eIF4E complexed to eIF4G (eIF4E ⋅ eIF4G), eIF4E binding protein 1 (4E-BP1) complexed to eIF4E, and phosphorylation state of eIF4E and 4E-BP1 (γ-form) were assessed in gastrocnemius. Rates of protein synthesis were higher in exercised rats compared with sedentary rats [205 ± 8 (SE) vs. 164 ± 5.5 nmol phenylalanine incorporated ⋅ g muscle−1 ⋅ h−1, respectively; P < 0.05]. Arterial plasma insulin concentrations were not different between the two groups. A trend ( P = 0.09) for an increase in eIF4E ⋅ eIF4G with exercise was noted; however, no statistically significant differences were observed in any of the components of the eIF4E family in response to resistance exercise. These new data, along with our previous report on eIF2B, suggest that the regulation of peptide chain initiation after exercise is more dependent on eIF2B than on the eIF4E system.

scholarly journals Severe diabetes prohibits elevations in muscle protein synthesis after acute resistance exercise in rats

2000 ◽  
Vol 88 (1) ◽  
pp. 102-108 ◽  
Author(s):  
Mark J. Fedele ◽  
Jazmir M. Hernandez ◽  
Charles H. Lang ◽  
Thomas C. Vary ◽  
Scot R. Kimball ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Growth Factor ◽  
Resistance Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Critical Concentration ◽  
Diabetic Rats ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Growth Factor I

This study determined whether rates of protein synthesis increase after acute resistance exercise in skeletal muscle from severely diabetic rats. Previous studies consistently show that postexercise rates of protein synthesis are elevated in nondiabetic and moderately diabetic rats. Severely diabetic rats performed acute resistance exercise ( n= 8) or remained sedentary ( n = 8). A group of nondiabetic age-matched rats served as controls ( n = 9). Rates of protein synthesis were measured 16 h after exercise. Plasma glucose concentrations were >500 mg/dl in the diabetic rats. Rates of protein synthesis (nmol phenylalanine incorporated ⋅ g muscle−1 ⋅ h−1, means ± SE) were not different between exercised (117 ± 7) and sedentary (106 ± 9) diabetic rats but were significantly ( P < 0.05) lower than in sedentary nondiabetic rats (162 ± 9) and in exercised nondiabetic rats (197 ± 7). Circulating insulin concentrations were 442 ± 65 pM in nondiabetic rats and 53 ± 11 and 72 ± 19 pM in sedentary and exercised diabetic rats, respectively. Plasma insulin-like growth factor I concentrations were reduced by 33% in diabetic rats compared with nondiabetic rats, and there was no difference between exercised and sedentary diabetic rats. Muscle insulin-like growth factor I was not affected by resistance exercise in diabetic rats. The results show that there is a critical concentration of insulin below which rates of protein synthesis begin to decline in vivo. In contrast to previous studies using less diabetic rats, severely diabetic rats cannot increase rates of protein synthesis after acute resistance exercise.

scholarly journals Exercise training initiated after the onset of diabetes preserves myocardial function: effects on expression of β-adrenoceptors

2008 ◽  
Vol 105 (3) ◽  
pp. 907-914 ◽  
Author(s):  
Keshore R. Bidasee ◽  
Hong Zheng ◽  
Chun-Hong Shao ◽  
Sheeva K. Parbhu ◽  
George J. Rozanski ◽  
...  
Keyword(s):  
Exercise Training ◽  
Cardiac Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Sprague Dawley ◽  
Western Blots ◽  
Sprague Dawley Rats ◽  
Function Loss ◽  
Onset Of Diabetes ◽  
Exercise Induced

The present study was undertaken to assess cardiac function and characterize β-adrenoceptor subtypes in hearts of diabetic rats that underwent exercise training (ExT) after the onset of diabetes. Type 1 diabetes was induced in male Sprague-Dawley rats using streptozotocin. Four weeks after induction, rats were randomly divided into two groups. One group was exercised trained for 3 wk while the other group remained sedentary. At the end of the protocol, cardiac parameters were assessed using M-mode echocardiography. A Millar catheter was also used to assess left ventricular hemodynamics with and without isoproterenol stimulation. β-Adrenoceptors were assessed using Western blots and [3H]dihydroalprenolol binding. After 7 wk of diabetes, heart rate decreased by 21%, fractional shortening by 20%, ejection fraction by 9%, and basal and isoproterenol-induced dP/d t by 35%. β1- and β2-adrenoceptor proteins were reduced by 60% and 40%, respectively, while β3-adrenoceptor protein increased by 125%. Ventricular homogenates from diabetic rats bound 52% less [3H]dihydroalprenolol, consistent with reductions in β1- and β2-adrenoceptors. Three weeks of ExT initiated 4 wk after the onset of diabetes minimized cardiac function loss. ExT also blunted loss of β1-adrenoceptor expression. Interestingly, ExT did not prevent diabetes-induced reduction in β2-adrenoceptor or the increase of β3-adrenoceptor expression. ExT also increased [3H]dihydroalprenolol binding, consistent with increased β1-adrenoceptor expression. These findings demonstrate for the first time that ExT initiated after the onset of diabetes blunts primarily β1-adrenoceptor expression loss, providing mechanistic insights for exercise-induced improvements in cardiac function.

Time course evaluation of protein synthesis and glucose uptake after acute resistance exercise in rats

2000 ◽  
Vol 88 (3) ◽  
pp. 1142-1149 ◽  
Author(s):  
Jazmir M. Hernandez ◽  
Mark J. Fedele ◽  
Peter A. Farrell
Keyword(s):  
Protein Synthesis ◽  
Resistance Exercise ◽  
Glucose Uptake ◽  
Time Course ◽  
Course Evaluation ◽  
Pi3 Kinase ◽  
Sprague Dawley ◽  
Phosphatidylinositol 3 Kinase ◽  
Sprague Dawley Rats

The temporal pattern for changes in rates of protein synthesis and glucose uptake after resistance exercise, especially relative to each other, is not known. Male Sprague-Dawley rats performed acute resistance exercise ( n = 7) or remained sedentary ( n = 7 per group), and the following were assessed in vivo 1, 3, 6, 12 and 24 h later: rates of protein synthesis, rates of glucose uptake, phosphatidylinositol 3-kinase (PI3-kinase) activity, and p70S6k activity. Rates of protein synthesis in mixed gastrocnemius muscle did not increase until 12 h after exercise (e.g., at 12 h, sedentary = 138 ± 4 vs. exercised = 178 ± 6 nmol phenylalanine incorporated ⋅ g muscle− 1 ⋅ h− 1, mean ± SE, P < 0.05), whereas at 6 h after exercise rates of glucose uptake were significantly elevated (sedentary = 0.18 ± 0.020 vs. exercised = 0.38 ± 0.024 μmol glucose 6-phosphate incorporated ⋅ kg muscle− 1 ⋅ min− 1, P < 0.05). At 24 h after exercise, rates of protein synthesis were still elevated, whereas glucose uptake had returned to basal levels. Arterial insulin concentrations were not different between groups at any time. Non-insulin-stimulated activities of PI3-kinase and p70S6k were higher at 6, 12, and 24 h after exercise ( P < 0.05), and, generally, these occurred when rates of protein synthesis (12 and 24 h) and glucose uptake were elevated (6 and 12 but not 24 h) by exercise. These data suggest that regulators of protein synthesis and glucose uptake may respond to the same contraction-generated signals with different kinetics or that they respond to different intra- or extracellular signals that are generated by exercise.

Insulin-facilitated increase of muscle protein synthesis after resistance exercise involves a MAP kinase pathway

2006 ◽  
Vol 290 (6) ◽  
pp. E1205-E1211 ◽  
Author(s):  
James D. Fluckey ◽  
Micheal Knox ◽  
Latasha Smith ◽  
Esther E. Dupont-Versteegden ◽  
Dana Gaddy ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Resistance Exercise ◽  
Signaling Pathways ◽  
Kinase Inhibitor ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Primary Component ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Recent studies have implicated the mTOR-signaling pathway as a primary component for muscle growth in mammals. The purpose of this investigation was to examine signaling pathways for muscle protein synthesis after resistance exercise. Sprague-Dawley rats (male, 6 mo old) were assigned to either resistance exercise or control groups. Resistance exercise was accomplished in operantly conditioned animals using a specially designed flywheel apparatus. Rats performed two sessions of resistance exercise, separated by 48 h, each consisting of 2 sets of 25 repetitions. Sixteen hours after the second session, animals were killed, and soleus muscles were examined for rates of protein synthesis with and without insulin and/or rapamycin (mTOR inhibitor) and/or PD-098059 (PD; MEK kinase inhibitor). Results of this study demonstrated that rates of synthesis were higher ( P < 0.05) with insulin after exercise compared with without insulin, or to control muscles, regardless of insulin. Rapamycin lowered ( P < 0.05) rates of synthesis in controls, with or without insulin, and after exercise without insulin. However, insulin was able to overcome the inhibition of rapamycin after exercise ( P < 0.05). PD had no effect on protein synthesis in control rats, but the addition of PD to exercised muscle resulted in lower ( P < 0.05) rates of synthesis, and this inhibition was not rescued by insulin. Western blot analyses demonstrated that the inhibitors used in the present study were selective and effective for preventing activation of specific signaling proteins. Together, these results suggest that the insulin-facilitated increase of muscle protein synthesis after resistance exercise requires multiple signaling pathways.

scholarly journals A comparison of 2H2O and phenylalanine flooding dose to investigate muscle protein synthesis with acute exercise in rats

2009 ◽  
Vol 297 (1) ◽  
pp. E252-E259 ◽  
Author(s):  
Heath G. Gasier ◽  
Steven E. Riechman ◽  
Michael P. Wiggs ◽  
Stephen F. Previs ◽  
James D. Fluckey
Keyword(s):  
Protein Synthesis ◽  
Resistance Exercise ◽  
High Intensity ◽  
Acute Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Primary Objective ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Single Bout

The primary objective of this investigation was to determine whether 2H2O and phenylalanine (Phe) flooding dose methods yield comparable fractional rates of protein synthesis (FSR) in skeletal muscle following a single bout of high-intensity resistance exercise (RE). Sprague-Dawley rats were assigned by body mass to either 4-h control (CON 4 h; n = 6), 4-h resistance exercise (RE 4 h; n = 6), 24-h control (CON 24 h; n = 6), or 24-h resistance exercise (RE 24 h; n = 6). The RE groups were operantly conditioned to engage in a single bout of high-intensity, “squat-like” RE. All rats were given an intraperitoneal injection of 99.9% 2H2O and provided 4.0% 2H2O drinking water for either 24 ( n = 12) or 4 h ( n = 12) prior to receiving a flooding dose of l-[2,3,4,5,6-3H]Phe 16 h post-RE. Neither method detected an effect of RE on FSR in the mixed gastrocnemius, plantaris, or soleus muscle. Aside from the qualitative similarities between methods, the 4-h 2H2O FSR measurements, when expressed in percent per hour, were quantitatively greater than the 24-h 2H2O and Phe flooding in all muscles ( P < 0.001), and the 24-h 2H2O was greater than the Phe flooding dose in the mixed gastrocnemius and plantaris ( P < 0.05). In contrast, the actual percentage of newly synthesized protein was significantly higher in the 24- vs. 4-h 2H2O and Phe flooding dose groups ( P < 0.001). These results suggest that the methodologies provide “qualitatively” similar results when a perturbation such as RE is studied. However, due to potential quantitative differences between methods, the experimental question should determine what approach should be used.

Kidney insulin-like growth factor-I mRNA levels are increased in postpubertal diabetic rats

1991 ◽  
Vol 129 (1) ◽  
pp. 5-10 ◽  
Author(s):  
L. A. Bach ◽  
J. L. Stevenson ◽  
T. J. Allen ◽  
G. Jerums ◽  
A. C. Herington
Keyword(s):  
Growth Factor ◽  
Northern Blotting ◽  
Diabetic Rats ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Sprague Dawley ◽  
Factor I ◽  
Igf I ◽  
Renal Enlargement ◽  
Growth Factor I

ABSTRACT Diabetes-associated renal enlargement is more marked in postpubertal than prepubertal rats, and in the postpubertal rat, is associated with increased kidney insulin-like growth factor-I (IGF-I) levels for the first 2 days. In order to determine whether local IGF-I production is the cause of this increase in tissue levels, IGF-I mRNA levels were determined in pre- and postpubertal Sprague–Dawley rats made diabetic with streptozotocin (STZ) and in control rats. RNA was extracted from kidneys and livers of rats at 0 h, 6 h, 12 h and days 1, 2, 3 and 7 after STZ injection. After Northern blotting and hybridization with an oligonucleotide probe complementary to an E domain of the IGF-I cDNA, four distinct bands (7·4, 4·8, 1·8 and 1·0 kb) were found. Densitometric analyses of the most prominent bands (7·4 and 1·0 kb), after normalization for 18S ribosomal RNA content, revealed a 50–100% increase in the kidneys of postpubertal diabetic rats compared with postpubertal controls 12 h after STZ injection (P < 0·05, diabetes vs control). Between days 2 and 7, kidney IGF-I mRNA levels in postpubertal diabetic rats fell to approximately 50% of control levels (P < 0·05, diabetes vs control). In contrast, kidney IGF-I mRNA levels in the prepubertal diabetic rats remained unchanged over the 7 days. Liver IGF-I mRNA levels did not rise during the first 24 h and fell to approximately 60% of control levels by day 7 in both pre- and postpubertal diabetic rats (P < 0·05, diabetes vs control). Increased local IGF-I production may underlie the initiation of renal enlargement associated with diabetes mellitus. Journal of Endocrinology (1991) 129, 5–10

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