Effects of type 1 diabetes mellitus on skeletal muscle: clinical observations and physiological mechanisms

Krause, Matthew P.; Riddell, Michael C.; Hawke, Thomas J.

doi:10.1111/j.1399-5448.2010.00699.x

Cited by 138 publications

(156 citation statements)

References 200 publications

(380 reference statements)

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“…Unfortunately for many young people with diabetes, glycaemic control during adolescence deteriorates [5] precisely at the same time when skeletal muscle would normally be rapidly growing [3]. Epidemiological evidence also suggests that youth with diabetes are less physically active and less engaged in sporting activities than their nondiabetic peers [27], which may help to explain, at least in part, their reduced physical capacities [28].…”

Section: Discussionmentioning

confidence: 99%

“…For this, 20 min after the oral gavage, rats were restrained in a cloth blanket and given a flooding dose of radiolabelled phenylalanine (1 ml/100 g body weight of 150 mmol/l L- [2,3,4,5, H]phenylalanine containing 1.85 MBq/ml) intraperitoneally. After 10 min, the animals were killed by decapitation.…”

Section: Designmentioning

confidence: 99%

“…Although the Diabetes Control and Complications Trial demonstrated that body mass was considerably lower in conventionally treated youth when compared with intensively treated youth, no body composition analysis was performed [4]. Compared with non-diabetic youth, adolescents with diabetes may be shorter, weaker and have a lower exercise capacity, particularly if they are under poor glycaemic control [3]. Insulin provision does not increase rates of whole body protein synthesis but rather lowers rates of protein degradation [1,7].…”

Section: Introductionmentioning

confidence: 99%

“…Type 1 diabetes mellitus is associated with impairments in protein metabolism that can result in muscle wasting, impaired muscular development and a lifetime of reduced physical and functional capacities [1][2][3]. Altered protein metabolism in diabetes may be particularly evident in the paediatric population where optimal insulin therapy and glycaemic control are difficult to achieve [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…The partially pancreatectomised (Px) rat is one model of choice, as it mimics hypoinsulinaemia/hyperglycaemia, with some basal insulin production, which is similar to a child with diabetes at the time of diabetes diagnosis or a child who is receiving inadequate insulin administration. Poor glycaemic control in young rodent models of diabetes is associated with reduced muscle growth, function and repair, at least in sedentary cage conditions [3,[8][9][10]. Impairments in growth occur particularly in the type II/ glycolytic fibres, in part because of decreased rates of muscle protein synthesis [11][12][13] and probably through a reduced capacity of mammalian target of rapamycin complex 1 (mTORC1) signalling in response to protein intake [9].…”

Section: Introductionmentioning

confidence: 99%

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Voluntary physical activity and leucine correct impairments in muscle protein synthesis in partially pancreatectomised rats

et al. 2011

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Aims/hypothesis Poorly controlled type 1 diabetes mellitus can cause reduced skeletal muscle mass and weakness during adolescence, which may affect long-term management of the disease. The aim of this study was to determine whether regular voluntary physical activity and leucine feeding restore rates of protein synthesis and deficits in skeletal muscle mass in a young, hypoinsulinaemic/hyperglycaemic rat model of diabetes. Methods Four-week-old male Sprague-Dawley rats were partially pancreatectomised (Px) to induce hypoinsulinaemia/hyperglycaemia and housed with/without access to running wheels for 3 weeks (n=12-14/group). Sham surgery rats (shams) served as sedentary controls (n=18). Protein synthesis and markers of protein anabolism were assessed in the fasted state and following leucine gavage.Fibre type and cross-sectional areas of the gastrocnemius muscle were measured using a metachromatic ATPase stain. Results Compared with sedentary behaviour, regular activity lowered fasting glycaemia and reduced fed hyperglycaemia in Px rats. Active-Px rats, which ran 2.2±0.71 km/night, displayed greater muscle mass and fibre areas similar to shams, while sedentary-Px rats displayed a 20-30% loss in muscle fibre areas. Muscle protein synthesis (basal and in response to leucine gavage) was impaired in sedentary-Px (by~65%), but not in active-Px rats, when compared with shams. Following leucine gavage, the phosphorylation status of eIF4E binding protein 1 (4E-BP1) and ribosomal S6 kinase 1 (S6K1), markers of mammalian target of rapamycin complex 1 (mTORC1) signalling, increased in shams (by two-and ninefold, respectively) and in active-Px (1.5-and fourfold, respectively) rats, but not in sedentary-Px rats. Conclusion/interpretation Moderate physical activity in young Px rats normalises impairments in skeletal muscle growth and protein synthesis. These findings illustrate the critical compensatory role that modest physical activity and targeted nutrition can have on skeletal muscle growth during periods of hypoinsulinaemia in adolescent diabetes.

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