Skeletal Muscle Metabolism in the Pathology and Treatment of Type 1 Diabetes

Abstract

Type 1 diabetes is characterised by the absence of circulating insulin due to the autoimmune destruction of beta-cells in the pancreas. Patients are traditionally treated with multiple daily injections of exogenous insulin analogues. However, although these therapies improve quality of life, they are associated with the risk of hypoglycemic episodes and do not prevent the development of debilitating secondary complications. For these reasons, there is increasing demand for new therapies and preventions. One approach is the use of viral or non-viral gene therapy to modify skeletal muscle to produce and secrete insulin into the circulation and/or to increase muscle glucose uptake. Skeletal muscle is a desirable target tissue for the treatment of diabetes not only for its central role in whole body metabolism and glucose homeostasis, but also for its accessibility and amenability to many potential gene therapy technologies. Here, we review the basic metabolic principles of skeletal muscle in the absorptive and post-absorptive states at rest and during exercise and discuss how these processes are affected in type 1 diabetes. Finally, current viral and non-viral strategies for modification of skeletal muscle and their application to the treatment of type 1 diabetes are also presented.

Exercise Increases Insulin Content and Basal Secretion in Pancreatic Islets in Type 1 Diabetic Mice

“…There are two general sites where exercise could directly affect blood glucose regulation: (1) insulin secretion of the islets and (2) insulin-stimulated glucose uptake in the skeletal muscle [18, 25, 26]. Only two papers have directly tested the first possibility: changes in insulin levels with exercise in T1D.…”

Influence of reaction and diffusion on spatial organization of mitochondria and effectiveness factors in skeletal muscle cell design

“…Bioengineering of muscle tissue is important for two general applications; the development of replacement tissue and the utilization of muscle as an in situ “bioreactor” for metabolic processes that might be added, for example, using gene therapy techniques (Ambrosio et al, 2010; Chromiak et al, 1998; Dennis et al, 2009; Lu et al, 2003; Mann et al, 2010; Walter et al, 2000; Weining and Bursac, 2008). In addition, skeletal muscle tissue is of central importance to whole animal function and it plays an important role in many diseases where its malfunction or failure may lead not only to the functional compromise of the affected site, but also to structural deformation.…”

Antidiabetic activity of gossypin, a pentahydroxyflavone glucoside, in streptozotocin‐induced experimental diabetes in rats

“…The glucose tolerance test is a measure of effective glucose utilization by the system and generally helps in the early diagnosis of diabetes 22 . In diabetes, impaired glucose tolerance develops predominantly as a result of the reduced uptake of glucose by the peripheral tissues, especially skeletal muscle 23 . Streptozotocin‐induced experimental diabetes results in a reduction in body weight that is associated with abnormalities in food and water intake.…”

“…22 In diabetes, impaired glucose tolerance develops predominantly as a result of the reduced uptake of glucose by the peripheral tissues, especially skeletal muscle. 23 Streptozotocin-induced experimental diabetes results in a reduction in body weight that is associated with abnormalities in food and water intake. In the present study, the administration of gossypin to diabetic rats for 30 days resulted in improved glucose tolerance and hence a significant body weight gain compared with diabetic rats.…”