Dehydroepiandrosterone treatment attenuates oestrogen-induced pituitary hyperplasia

The physiological importance of and therapeutic interest in dehydroepiandrosterone (DHEA) has been predominantly in relation to its action as an inhibitor of the promotion and progression of several kinds of tumours, including those of breast, prostate, lung, colon, liver and skin tissues. The aim of the present study was to determine the role of DHEA in diethylstilboestrol (DES)-induced pituitary hyperplasia. Female Sprague-Dawley rats were divided into four treatment groups: DES (implanted s.c. with a 20 mg DES pellet), DHEA (two 50 mg DHEA pellets), DHEA/DES (both DHEA and DES pellets), and controls (not implanted). Every week, all rats were weighed and cycled, and jugular blood samples were obtained. After 7 weeks, rats were killed. Hypophyses were removed and weighed, and serum prolactin, GH, IGF-I and leptin levels were assayed by RIA. DHEA cotreatment reduced pituitary enlargement by 39% in DES-treated rats. It also reduced the hyperprolactinaemia (280.4+/-43.6 ng/ml for DHEA/DES vs 823.5+/- 127.1 ng/ml for DES) and partially reversed the loss of body weight induced by DES. DHEA treatment did not modify the effects of DES on serum GH, IGF-I and leptin levels. But DHEA per se also increased pituitary weight and induced hyperprolactinaemia, although to a lesser degree than DES. We conclude that DHEA administration has beneficial effects on oestrogen-induced pituitary hyperplasia and hyperprolactinaemia, but the fact that DHEA per se also induces diverse hormonal effects and a slight pituitary enlargement limits its use as a possible therapeutic drug.

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Abstract 131: Anti-inflammatory and Mitochondrial Effects of Butyrate in Shr Astrocytes in vitro

Circulation Research ◽

10.1161/res.121.suppl_1.131 ◽

2017 ◽

Vol 121 (suppl_1) ◽

Author(s):

Tao Yang ◽

Ty Redler ◽

Carla G Bueno Silva ◽

Rebeca Arocha ◽

Jordan Schmidt ◽

...

Keyword(s):

Mitochondrial Function ◽

Mitochondrial Respiration ◽

Rna Isolation ◽

Inflammatory Factors ◽

Pcr Analysis ◽

Sprague Dawley ◽

Beneficial Effects ◽

Sd Rats ◽

Anti Inflammatory

Emerging evidence demonstrates a significant link between gut dysbiosis and hypertension (HTN). Butyrate is one of the major fermented end-products of gut microbiota that reportedly produces beneficial effects on the immune system and metabolism. A contraction in butyrate-producing bacteria in the gut of spontaneously hypertensive rats (SHR) suggests that reduced butyrate may be associated with HTN. Considering its role in mitochondrial metabolism, we proposed that the positive anti-inflammatory effects of butyrate may be mediated via improvement in mitochondrial function in astrocytes. Methods: Sprague Dawley (SD) and SHR primary astrocytes from two-day old pups were cultured in DMEM, supplemented with 10% FBS and 1% pen/strep, for 14 days, prior to treatment with butyrate (0-1mM) for 4 hours. Cells were then subjected to the Seahorse XFe24 Extracellular Flux Analyzer to evaluate mitochondrial function following butyrate treatment. Additional samples were collected for total RNA isolation for real time PCR analysis of inflammatory factors and transcripts related to mitochondrial function and stress. Results: Butyrate significantly increased both basal and maximal mitochondrial respiration (by 3-4 fold, P<0.001) and elevated proton leak (by 4 fold, P<0.01) in astrocytes from SD rats but not SHR. Furthermore, we observed a trend for an increase in both ATP-linked and non-mitochondrial respiration in SD astrocytes compared to SHR (by 2-3 fold, P=0.07). This was associated with a significant reduction in relative expression levels in catalase (by 50%, P<0.05) and a trend in reduction in Sod1 and Sod2 (by 25%-50%, P=0.1) in astrocytes harvested from SD rats but not the SHR. Conversely, butyrate significantly lowered expression of pro-inflammatory Ccl2 (by 33%, P<0.05) and Tlr4 (by 48%, P <0.05) in astrocytes of SHR, but not SD rats. Conclusion: Butyrate modulated mitochondrial bioenergetics in SD but not the SHR, suggesting that the mitochondria of astrocytes may be less sensitive to the effects of butyrate in HTN. In addition, butyrate reduced inflammatory mediators in the SHR, but had no effect in the SD rat astrocytes. Thus, central anti-inflammatory effects of butyrate may be mediated via a mitochondria-independent mechanism.

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Salvia Officinalis Protects Pancreatic Beta-cells Against Streptozotocin-Induced Damage; A Stereological Study

Jundishapur Journal of Natural Pharmaceutical Products ◽

10.5812/jjnpp.109906 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Soheil Ashkani-Esfahani ◽

Ali Noorafshan ◽

Alireza Ebrahimi ◽

Maryam Bahmani-Jahromi ◽

Mohammad-Hossein Imanieh ◽

...

Keyword(s):

Beta Cells ◽

Pancreatic Beta Cells ◽

Pancreatic Injury ◽

Food Supplement ◽

Salvia Officinalis ◽

Diabetic Group ◽

Protective Effects ◽

Sprague Dawley ◽

Beneficial Effects ◽

Patients With Diabetes

Background: Diabetes mellitus (DM) is a chronic disease, progressing due to inadequate secretion of insulin by pancreas. Salvia officinalis (SVO) has anti-inflammatory and anti-oxidative potentials, which may be beneficial in regulating underlying causes of DM. Objectives: In this study, we aimed to estimate the protective effects of SVO against Streptozotocin (STZ)-induced pancreatic injury in rat models of DM. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups (n = 12); C1: normal group with no treatment, C2: diabetic group with no treatment, E1: diabetic group treated with 200 mg/kg of the SVO extract, and E2: diabetic group treated with 400 mg/kg of the SVO extract. All groups received a single dose of STZ on day 7 except C1. Pancreas volume, shrinkage, volume densities of the islets, numerical densities, and volume of the beta cells were measured using stereological methods. Results: Blood sugar (BS) levels were significantly lower in SVO-treated groups comparing to C2 group. Also, volume densities and total number of islets and beta cells in E1 and E2 groups were higher than C2 (P < 0.05), but lower than C1 (P < 0.05). Volume densities of the islets and beta cells, and total number of beta cells in E1, and volume densities of the islets and beta cells in E2 groups were considerably higher than C2 group (P < 0.05). Conclusions: Our result showed the beneficial effects of SVO extract regarding pancreatic damage. We concluded that SVO might be prescribed as a therapeutic food supplement for patients with diabetes.

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Discovery of Serum Proteomic Biomarkers for Prediction of Response to Moxibustion Treatment in Rats with Collagen-Induced Arthritis: An Exploratory Analysis

Acupuncture in Medicine ◽

10.1136/acupmed-2015-010909 ◽

2016 ◽

Vol 34 (3) ◽

pp. 184-193 ◽

Cited By ~ 10

Author(s):

Xiao Xu ◽

Miao-Miao Wang ◽

Zhi-ling Sun ◽

Dan-ping Zhou ◽

Ling Wang ◽

...

Keyword(s):

Rat Model ◽

Multiple Testing ◽

Day Treatment ◽

Expression Patterns ◽

Control Group ◽

Sprague Dawley ◽

Collagen Induced Arthritis ◽

Serum Samples ◽

Beneficial Effects ◽

Bovine Collagen

Objective To examine the possible impact of moxibustion on the serum proteome of the collagen-induced arthritis (CIA) rat model. Materials and Methods Thirty-six male Sprague-Dawley rats were included in this experiment. The CIA animal model was prepared by injection of type II bovine collagen in Freund's adjuvant on the first and seventh day. The 36 rats were randomly divided into two groups: the untreated CIA group (control), and the CIA plus treatment with moxibustion (CIA+moxi) group. Moxibustion was administered daily at ST36 and BL23 for 7, 14 or 21 days (n=12 rats each). Arthritis score was used to assess the severity of arthritis. At the end of each 7 day treatment, blood samples from the control group and the CIA+moxi group were collected. After removal of high abundance proteins from serum samples, two-dimensional gel combined with matrix-assisted laser desorption ionisation time-of-flight MS/MS (MALDI-TOF-MS/MS) techniques were performed to examine serum protein expression patterns of the CIA rat model with and without moxibustion treatment. In addition, the relevant proteins were further analysed with the use of bioinformatics analysis. Results Moxibustion significantly decreased arthritis severity in the rats in the CIA+moxi group, when compared with the rats in the CIA group 35 days after the first immunisation (p=0.001). Seventeen protein spots which changed >1.33 or <0.77 at p<0.05 using Bonferonni correction for multiple testing were found to be common to all three comparisons, and these proteins were used for classification of functions using the Gene Ontology method. Consequently, with the use of the Ingenuity Pathway Analysis, the top canonical pathways and a predicted proteomic network related to the moxibustion effect of CIA were established. Conclusions Using the proteomics technique, we have identified novel candidate proteins that may be involved in the mechanisms of action underlying the beneficial effects of moxibustion in rats with CIA. Our findings suggest that immune responses and metabolic processes may be involved in mediating the effects of moxibustion. Moreover, periodxiredoxin I (PRDX1) and inositol 1,4,5-triphosphate receptor (IP3R) may be potential targets.

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Abstract P289: Cardio-protective Peptide Ac-SDKP is Highly Concentrated in Lymph Nodes

Hypertension ◽

10.1161/hyp.70.suppl_1.p289 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Cesar A Romero ◽

Sonal Vaid ◽

Nitin Kumar ◽

Tang-Dong Liao ◽

Oscar A Carretero

Keyword(s):

Lymph Node ◽

Target Organ Damage ◽

Organ Damage ◽

Giant Cells ◽

Rat Tissues ◽

Cortical Region ◽

Sprague Dawley ◽

Beneficial Effects ◽

Sd Rats ◽

Natural Peptide

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a natural peptide released from its precursor Thymosin β4 (Tβ4) by meprin-α and the prolyl oligopeptidase enzymes (POP) in sequential steps. Ac-SDKP is hydrolyzed by the angiotensin converting enzyme (ACE). Ac-SDKP has anti-inflammatory and anti-fibrotic effects in heart, aorta and kidney and part of the beneficial effects of ACE inhibitors has been ascribed to the increased levels of Ac-SDKP. Ac-SDKP is present in spleen and thymus, however, the presence of Ac-SDKP in the lymph node has not been studied. We hypothesized that Tβ4, Ac-SDKP and its releasing enzymes are present in lymph node. Ac-SDKP concentration was evaluated in Sprague-Dawley (SD) rat tissues. Tβ4 as well as Meprin-α and POP enzymes were measured in the lymph node, thymus, spleen and other tissues obtained from SD rats. Additionally, Ac-SDKP content was measured in different cell populations of lymph node obtained through cell sorting. Lymph node showed the highest Ac-SDKP concentration (181±18.3 ng/mg of protein), followed by the testis (104.3±6.5, thymus (54.2±1.8) and spleen (44.9±4.7) in SD rats (P<0.001 lymph node vs. testis, thymus and spleen). Meprin-α and POP activity were present in lymph node, spleen and thymus. Tβ4 and Meprin-α immunostaining were found to be positive in multinucleated giant cells in the cortical region of lymph node and along the septums; it was also found in the follicular region and germinal center. POP staining was found positive in the cortical region. In the lymph node, Ac-SDKP concentration was higher in Macrophages (CD45+CD68+) in comparison with T lymphocytes (CD45+CD3+) (150±110 pmol/100,000 cell vs. 0.3±0.1pmol/100,000cell, respectively). We conclude that in lymph node, Ac-SDKP is highly concentrated and that all the components of Tβ4/Ac-SDKP system are present. Macrophages could be the main source of Ac-SDKP in lymph node. The presence of Ac-SDKP in lymph node may have important implications in understanding inflammation and target organ damage in cardiovascular diseases.

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THE VALUE OF PENICILLIN IN THE TREATMENT OF AGRANULOCYTOSIS CAUSED BY THIOURACIL

Blood ◽

10.1182/blood.v1.1.53.53 ◽

1946 ◽

Vol 1 (1) ◽

pp. 53-66 ◽

Cited By ~ 6

Author(s):

MARY CATHERINE TYSON ◽

PETER VOGEL ◽

NATHAN ROSENTHAL

Keyword(s):

Bone Marrow ◽

Antibacterial Agents ◽

Bone Marrow Cells ◽

The Body ◽

Bacterial Invasion ◽

Beneficial Effects ◽

Penicillin Therapy ◽

History Of ◽

Per Se ◽

Hemopoietic System

Abstract Thiouracil has been found to be an effective drug in the treatment of hyperthyroidism. Agranulocytosis following its use occurred in nine cases, four of which terminated fatally. In five others a complete and rapid recovery took place following penicillin therapy. The latter drug is believed to be ideal for all cases of agranulocytosis, and especially those in which chemotherapy has been used and may have been responsible for the condition. Thus far we have not seen any report of any untoward effect on the hemopoietic system from the use of penicillin. The use of antibacterial agents for the treatment of agranulocytosis was suggested by Dameshek and Wolfson21 in 1942. It was believed by these authors that patients with agranulocytosis died not of the leukopenia per se but of the sepsis which developed secondarily to the lack of granulocytes. Two very severe cases of aminopyrine agranulocytosis treated with sulfathiazole made complete recoveries. For the treatment of sulfonamide agranulocytosis, it was suggested that a preparation differing from that which had already been used be given. With the discovery of penicillin, and its complete lack of possible deleterious effect on the bone marrow, its use was suggested by Dameshek17 (1944). A report on the beneficial effects of this medication in a case of sulfonamide agranulocytosis was later reported by Dameshek and Knowlton18 and similar cases by Sprague and Ferguson19 and by Meredith and Fink.20 Since sulfonamides may cause further toxic effect on the bone marrow, we feel that their use should be avoided in the treatment of agranulocytosis, especially where a history of previous use is obtained. We do not agree with others21, 22 who continue the use of sulfonamides in the treatment of leukopenia or agranulocytosis where these very drugs may have been responsible for the condition. It would seem better judgment to use penicillin, which by combating the bacterial invasion of the body and the consequent toxemia enables the patient to survive until the bone marrow cells regenerate.

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Role of Tonsillectomy and Adenoidectomy in the Management of Children with Middle Ear Effusion

Annals of Otology Rhinology & Laryngology ◽

10.1177/00034894800890s513 ◽

1980 ◽

Vol 89 (5_suppl) ◽

pp. 43-46 ◽

Cited By ~ 2

Author(s):

James B. Snow

Keyword(s):

Otitis Media ◽

Middle Ear ◽

Clinical Effectiveness ◽

First Year ◽

Middle Ear Effusion ◽

Beneficial Effects ◽

Per Se ◽

Second Year ◽

Ear Effusion

Evidence for the clinical effectiveness of adenoidectomy or tonsillectomy and adenoidectomy in the management of children with persistent middle ear effusions is incomplete and what evidence there is in the literature is not convincing. In the first year after tonsillectomy and adenoidectomy there is less otitis media. The beneficial effects of tonsillectomy and adenoidectomy on the incidence of otitis media declines in the second year after the operation. The prevailing opinion is that adenoidectomy is not indicated in the vast majority of children in whom a middle ear effusion has persisted for six weeks or more in spite of antibiotic therapy. Factors favoring an adenoidectomy would be persistent nasal obstruction, persistent purulent rhinorrhea and persistent adenoiditis. The role of tonsillectomy is even less clear, but the decision regarding tonsillectomy is made by most clinicians on the basis of the amount of intercurrent or chronic tonsillitis rather than on the basis of the middle ear effusion per se.

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Influence of Therapeutic Hypothermia on Matrix Metalloproteinase Activity after Traumatic Brain Injury in Rats

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9600150 ◽

2005 ◽

Vol 25 (11) ◽

pp. 1505-1516 ◽

Cited By ~ 80

Author(s):

Jessie S Truettner ◽

Ofelia F Alonso ◽

W Dalton Dietrich

Keyword(s):

Brain Injury ◽

Therapeutic Hypothermia ◽

Brain Injuries ◽

Brain Temperature ◽

Sprague Dawley ◽

Beneficial Effects ◽

Sprague Dawley Rats ◽

In Situ Zymography ◽

Metalloproteinase Activity

Recent evidence suggests that matrix metalloproteinases (MMPs) contribute to acute edema and lesion formation following ischemic and traumatic brain injuries (TBI). Experimental and clinical studies have also reported the beneficial effects of posttraumatic hypothermia on histopathological and behavioral outcome. The purpose of this study was to determine whether therapeutic hypothermia would affect the activity of MMPs after TBI. Male Sprague-Dawley rats were traumatized by moderate parasagittal fluid-percussion (F-P) brain injury. Seven groups ( n = 5/group) of animals were investigated: sham-operated, TBI with normothermia (37°C), and TBI with hypothermia (33°C). Normothermia animals were killed at 4, 24, 72 h and 5 days, and hypothermia animals at 24 or 72 h. Brain temperature was reduced to target temperature 30 mins after trauma and maintained for 4 h. Ipsilateral and contralateral cortical, hippocampal, and thalamic regions were analyzed by gelatin and in situ zymography. In traumatized normothermic animals, TBI significantly ( P<0.005) increased MMP-9 levels in ipsilateral (right) cortical and hippocampal regions, compared with contralateral or sham animals, beginning at 4 h and persisting to 5 days. At 1, 3, and 5 days after TBI, significant increases in MMP-2 levels were observed. In contrast to these findings observed with normothermia, posttraumatic hypothermia significantly reduced MMP-9 levels. Hypothermic treatment, however, did not affect the delayed activation of MMP-2. Clarifying the mechanisms underlying the beneficial effects of posttraumatic hypothermia is an active area of research. Posttraumatic hypothermia may attenuate the deleterious consequences of brain trauma by reducing MMP activation acutely.

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Iron Supplementation Confers Protection on Disease Severity in Dextran Sodium Sulfate (DSS)-Induced Colitis in Rats (OR15-05-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.or15-05-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Amanda Bries ◽

Rachel Derscheid ◽

Paige Curry ◽

Joe Webb ◽

Olivia Meier ◽

...

Keyword(s):

Disease Activity ◽

Iron Supplementation ◽

Iron Homeostasis ◽

Iron Status ◽

Fold Increase ◽

Deficiency Anemia ◽

State University ◽

Sprague Dawley ◽

Beneficial Effects ◽

Funding Sources

Abstract Objectives Koji iron, enriched with FeSO4 (Ultimine®; ULT), is a novel source of supplemental iron. Previously, we reported ULT had similar absorption as ferrous sulfate (FeSO4), while resulting in less reported adverse effects in women. Iron deficiency anemia is a common manifestation of inflammatory bowel disease (IBD) due to malabsorption and gastrointestinal (GI) bleeding. Therefore, the objective of our study was to identify the efficacy of 2 forms of iron supplementation on impaired GI integrity and anemia caused by dextran sulfate sodium (DSS)-induced colitis. Methods Six wk old Sprague Dawley rats (n = 40) were randomly assigned to one of four treatment groups (n = 10/group): 1) Control with no DSS; 2) Control + DSS only (Nfe); 3) DSS + ULT; 4) DSS + FeSO4. Animals were maintained on the AIN-93 G diets for 7 d. Colitis was induced by administering fresh 3.5% (w/v) DSS ad lib throughout the study. Daily iron supplementation (6 mg Fe/kg BW) was provided in a pulverized treat, and disease activity indices were observed (gross bleeding, stool consistency and weight loss). Histological scoring of colonic ulcerations, inflammation and grade were assessed. Iron status indicators and liver hepcidin were detected using ELISA and qRT-PCR, respectively. Results The severity score of IBD was significantly higher in the animals without iron supplementation than those treated with iron (P < 0.0001). Moreover, iron supplementation protected against diminished hemoglobin and hematocrit levels as a result of DSS treatment (P = 0.001 and P = 0.03, respectively); whereas, these parameters were not significantly (NS) different between ULT and FeSO4. Improvement was found with post mortem disease score of DSS-induced rats with ULT compared to FeSO4 and Nfe by 14% and 39%, respectively (NS). Compared to healthy controls, FeSO4 resulted in a 3.5-fold increase in liver hepcidin gene expression, whereas ULT caused no change. Conclusions The results of this study highlight the beneficial effects iron supplementation has on the disease activity evoked by severe GI inflammation. Furthermore, this data suggests ULT attenuates the progression of IBD by supporting iron homeostasis. Additional analyses will explore the possible mechanisms of these results by identifying the systemic inflammation. Funding Sources College of Human Sciences, Iowa State University Collaborative Seed Grant Program.

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Pegvisomant therapy in pituitary gigantism: successful treatment in a 12-year-old girl

Acta Endocrinologica ◽

10.1530/eje.1.01956 ◽

2005 ◽

Vol 153 (2) ◽

pp. 195-201 ◽

Cited By ~ 25

Author(s):

M Rix ◽

P Laurberg ◽

A S Hoejberg ◽

B Brock-Jacobsen

Keyword(s):

Well Being ◽

Lymphocytic Infiltration ◽

High Serum ◽

Serum Prolactin ◽

Great Promise ◽

Oral Glucose ◽

Somatostatin Analogue ◽

Tall Stature ◽

Gh Secretion ◽

Igf I

Objective: The use of a growth hormone (GH) receptor antagonist, pegvisomant has shown great promise in adults with acromegaly, but experience in paediatric patients is lacking. We aimed to describe the results of pegvisomant therapy in a 12-year-old girl with an aggressive GH-secreting pituitary tumour. Design: To evaluate the ability of pegvisomant therapy to control the effects of peripheral GH excess in a case of pituitary gigantism. Methods: Pegvisomant was introduced at 10 mg/day, given subcutaneously, and gradually increased to 20 mg/day until serum IGF-I was normal for age. Results: A large pituitary adenoma with suprasellar extension was diagnosed in a 12-year-old girl with progressive tall stature (178 cm), GH hypersecretion without suppression during oral glucose loading (nadir serum GH, 90 mU/l), high serum IGF-I and serum prolactin levels. Surgical extirpation was not possible because tumour tissue was fibrous and adherent to the optical nerves. Histological examination showed a mixed GH- and prolactin-secreting adenoma with lymphocytic infiltration of B and T cells. Treatment with a dopamine agonist, cabergoline, normalized serum prolactin, but GH secretion was resistant to both somatostatin analogue, octreotide and cabergoline. Radiation followed by pegvisomant therapy titrated up in dose to 20 mg/day led to a marked reduction in GH secretion and normalization of IGF-I, and to growth arrest and improvement of well-being. Conclusions: We suggest that treatment in pituitary gigantism with pegvisomant is safe and may normalize IGF-I levels and effectively stop growing.

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Regulation of protein synthesis after acute resistance exercise in diabetic rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1999.276.4.e721 ◽

1999 ◽

Vol 276 (4) ◽

pp. E721-E727 ◽

Cited By ~ 25

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.

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