Animal model of simulated microgravity: a comparative study of hindlimb unloading via tail versus pelvic suspension

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Abstract

The aim of this study was to compare physiological effects of hindlimb suspension (HLS) in tail- and pelvic-HLS rat models to determine if severe stretch in the tail-HLS rats lumbosacral skeleton may contribute to the changes traditionally attributed to simulated microgravity and musculoskeletal disuse in the tail-HLS model. Adult male Sprague-Dawley rats divided into suspended and control-nonsuspended groups were subjected to two separate methods of suspension and maintained with regular food and water for 2 weeks. Body weights, food and water consumption, soleus muscle weight, tibial bone mineral density, random plasma insulin, and hindlimb pain on pressure threshold (PPT) were measured. X-ray analysis demonstrated severe lordosis in tail- but not pelvic-HLS animals. However, growth retardation, food consumption, and soleus muscle weight and tibial bone density (decreased relative to control) did not differ between two HLS models. Furthermore, HLS rats developed similar levels of insulinopenia and mechanical hyperalgesia (decreased PPT) in both tail- and pelvic-HLS groups. In the rat-to-rat comparisons, the growth retardation and the decreased PPT observed in HLS-rats was most associated with insulinopenia. In conclusion, these data suggest that HLS results in mild prediabetic state with some signs of pressure hyperalgesia, but lumbosacral skeleton stretch plays little role, if any, in these pathological changes.

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Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues.

Kathryn Thrailkill, Ashley Fowlkes, R. Bunn … (2005)

Diabetic osteoporosis is increasingly recognized as a significant comorbidity of type 1 diabetes mellitus. In contrast, type 2 diabetes mellitus is more commonly associated with modest increases in bone mineral density for age. Despite this dichotomy, clinical, in vivo, and in vitro data uniformly support the concept that new bone formation as well as bone microarchitectural integrity are altered in the diabetic state, leading to an increased risk for fragility fracture and inadequate bone regeneration following injury. In this review, we examine the contribution that insulin, as a potential anabolic agent in bone, may make to the pathophysiology of diabetic bone disease. Specifically, we have assimilated human and animal data examining the effects of endogenous insulin production, exogenous insulin administration, insulin sensitivity, and insulin signaling on bone. In so doing, we present evidence that insulin, acting as an anabolic agent in bone, can preserve and increase bone density and bone strength, presumably through direct and/or indirect effects on bone formation.

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The hindlimb unloading rat model: literature overview, technique update and comparison with space flight data.

Emily Morey-Holton, Ruth K Globus, Alexander Kaplansky … (2005)

The hindlimb unloading rodent model is used extensively to study the response of many physiological systems to certain aspects of space flight, as well as to disuse and recovery from disuse for Earth benefits. This chapter describes the evolution of hindlimb unloading, and is divided into three sections. The first section examines the characteristics of 1064 articles using or reviewing the hindlimb unloading model, published between 1976 and April 1, 2004. The characteristics include number of publications, journals, countries, major physiological systems, method modifications, species, gender, genetic strains and ages of rodents, experiment duration, and countermeasures. The second section provides a comparison of results between space flown and hindlimb unloading animals from the 14-day Cosmos 2044 mission. The final section describes modifications to hindlimb unloading required by different experimental paradigms and a method to protect the tail harness for long duration studies. Hindlimb unloading in rodents has enabled improved understanding of the responses of the musculoskeletal, cardiovascular, immune, renal, neural, metabolic, and reproductive systems to unloading and/or to reloading on Earth with implications for both long-duration human space flight and disuse on Earth.

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Bed-rest-induced insulin resistance occurs primarily in muscle.

Charles Stuart, Robert E. Shangraw, Melvin Prince … (1988)

Treatment of trauma victims and patients with severe illness may contribute to their metabolic derangements by severely restricting physical activity. We sought to quantitate the impact of absolute bed rest alone on insulin regulation of glucose metabolism in six healthy subjects. Six to seven days of strict bed rest resulted in moderate deterioration in oral glucose tolerance and increased both fasting plasma insulin concentration and the insulin response to an oral glucose challenge by more than 40%. Euglycemic insulin clamp studies demonstrated the development of resistance to insulin's stimulation of whole-body glucose utilization. This change was characterized by a rightward shift of the insulin dose-response curve (insulin concentration at which 50% of maximal stimulation occurred was 45 +/- 3 (SE) microU/mL in the base line period and 78 +/- 8 microU/mL after seven days of bed rest, P less than .01) with little alteration in the maximal response in the rate of glucose uptake (baseline 15.4 +/- 1.4 mg/kg.min and bed rest 14.0 +/- 1.3 mg/kg.min). In contrast to the shift of sensitivity of whole-body glucose utilization to insulin, suppression of hepatic glucose output by insulin was unchanged by seven days of bed rest. Insulin binding to circulating mononuclear cells was not changed by bed rest. These studies demonstrate that the limited physical activity dictated by bed rest for as little as seven days is associated with substantial resistance to insulin's effects on glucose metabolism. Further, the data suggest that these effects occur primarily in skeletal muscle with little change in insulin action on the liver.

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Journal

Journal ID (nlm-ta): Physiol Rep

Journal ID (iso-abbrev): Physiol Rep

Journal ID (publisher-id): phy2

Title: Physiological Reports

Publisher: Blackwell Publishing Ltd

ISSN (Print): 2051-817X

ISSN (Electronic): 2051-817X

Publication date (Print): June 2013

Publication date (Electronic): 12 June 2013

Volume: 1

Issue: 1

Electronic Location Identifier: e00012

Affiliations

[1 ]Department of Physiology and Biophysics, University of Arkansas for Medical Sciences Little Rock, Arkansas, 72205

[2 ]Department of Anesthesiology, University of Arkansas for Medical Sciences Little Rock, Arkansas, 72205

[3 ]Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences Little Rock, Arkansas, 72205

Author notes

Maxim Dobretsov, Department of Anesthesiology, Slot 515, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205. Tel: 501-603-1936 Fax: 501-603-1951 E-mail: dobretsovmaxim@ 123456uams.edu

Funding Information This work was supported by UAMS COM pilot grant program and a grant from Arkansas Space Grant Consortium (ASGC).

Article

DOI: 10.1002/phy2.12

PMC ID: 3831940

PubMed ID: 24303103

SO-VID: fb0eb0da-c633-4f4d-a799-af3a420673d4

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Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

Animal model of simulated microgravity: a comparative study of hindlimb unloading via tail versus pelvic suspension

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Abstract

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Animal models of intrauterine growth restriction (IUGR)

Most cited references 51

Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues.

The hindlimb unloading rat model: literature overview, technique update and comparison with space flight data.

Bed-rest-induced insulin resistance occurs primarily in muscle.

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