Myostatin inhibition therapy for insulin-deficient type 1 diabetes
| Autor: | Samantha K. Coleman, Eric M. Desjardins, Thomas J. Hawke, Donna M. D’Souza, Irena A. Rebalka, Namita Deodhare |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty endocrine system diseases medicine.medical_treatment Myostatin Biology Article Diabetes Mellitus Experimental 03 medical and health sciences Mice Insulin resistance Internal medicine Diabetes mellitus medicine Animals Insulin RNA Messenger Muscle Skeletal Crosses Genetic Mice Knockout Type 1 diabetes Glucose Transporter Type 1 Multidisciplinary Glucose Transporter Type 4 Muscle Weakness Insulin tolerance test Skeletal muscle nutritional and metabolic diseases Genetic Therapy medicine.disease musculoskeletal system Founder Effect 3. Good health Mice Inbred C57BL 030104 developmental biology Endocrinology medicine.anatomical_structure Diabetes Mellitus Type 1 Glucose Gene Expression Regulation Hyperglycemia biology.protein Insulin Resistance GLUT4 Signal Transduction |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | While Type 1 Diabetes Mellitus (T1DM) is characterized by hypoinsulinemia and hyperglycemia, persons with T1DM also develop insulin resistance. Recent studies have demonstrated that insulin resistance in T1DM is a primary mediator of the micro and macrovascular complications that invariably develop in this chronic disease. Myostatin acts to attenuate muscle growth and has been demonstrated to be elevated in streptozotocin-induced diabetic models. We hypothesized that a reduction in mRNA expression of myostatin within a genetic T1DM mouse model would improve skeletal muscle health, resulting in a larger, more insulin sensitive muscle mass. To that end, Akita diabetic mice were crossed with MyostatinLn/Ln mice to ultimately generate a novel mouse line. Our data support the hypothesis that decreased skeletal muscle expression of myostatin mRNA prevented the loss of muscle mass observed in T1DM. Furthermore, reductions in myostatin mRNA increased Glut1 and Glut4 protein expression and glucose uptake in response to an insulin tolerance test (ITT). These positive changes lead to significant reductions in resting blood glucose levels as well as pronounced reductions in associated diabetic symptoms, even in the absence of exogenous insulin. Taken together, this study provides a foundation for considering myostatin inhibition as an adjuvant therapy in T1DM as a means to improve insulin sensitivity and blood glucose management. |
| Databáze: | OpenAIRE |
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