Bimodal Effect on Pancreatic β-Cells of Secretory Products From Normal or Insulin-Resistant Human Skeletal Muscle
| Autor: | Thierry Berney, Marc Y. Donath, Philippe A. Halban, Karim Bouzakri, Peter Plomgaard, Bente Karlund Pedersen |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Male
Muscle Fibers Skeletal/metabolism Protein-Serine-Threonine Kinases/genetics/metabolism Endocrinology Diabetes and Metabolism medicine.medical_treatment Muscle Fibers Skeletal Apoptosis Cell Proliferation/drug effects 0302 clinical medicine Insulin-Secreting Cells Insulin Secretion Insulin ddc:576.5 Cells Cultured 0303 health sciences ddc:617 Myogenesis Cytokines/metabolism medicine.anatomical_structure Insulin/metabolism/secretion Tumor Necrosis Factor-alpha/pharmacology Cytokines RNA Interference Tumor necrosis factor alpha Signal Transduction medicine.medical_specialty Insulin Receptor Substrate Proteins Insulin-Secreting Cells/drug effects/metabolism 030209 endocrinology & metabolism Protein Serine-Threonine Kinases Biology 03 medical and health sciences Insulin resistance Internal medicine Myokine In Situ Nick-End Labeling Internal Medicine medicine Animals Humans Rats Wistar Pancreatic hormone Cell Proliferation 030304 developmental biology Tumor Necrosis Factor-alpha Apoptosis/drug effects Insulin Receptor Substrate Proteins/genetics Skeletal muscle medicine.disease Culture Media Conditioned/metabolism/pharmacology Rats Endocrinology Culture Media Conditioned Insulin Resistance Insulin Resistance/physiology |
| Zdroj: | Diabetes, Vol. 60, No 4 (2011) pp. 1111-21 Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db10-1178 |
| Popis: | OBJECTIVE Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) β-cells. RESEARCH DESIGN AND METHODS Human skeletal muscle cells were cultured for up to 24 h with tumor necrosis factor (TNF)-α to induce insulin resistance, and mRNA expression for cytokines was analyzed and compared with controls (without TNF-α). Conditioned media were collected and candidate cytokines were measured by antibody array. Human and rat primary β-cells were used to explore the impact of exposure to conditioned media for 24 h on apoptosis, proliferation, short-term insulin secretion, and key signaling protein phosphorylation and expression. RESULTS Human myotubes express and release a different panel of myokines depending on their insulin sensitivity, with each panel exerting differential effects on β-cells. Conditioned medium from control myotubes increased proliferation and glucose-stimulated insulin secretion (GSIS) from primary β-cells, whereas conditioned medium from TNF-α–treated insulin-resistant myotubes (TMs) exerted detrimental effects that were either independent (increased apoptosis and decreased proliferation) or dependent on the presence of TNF-α in TM (blunted GSIS). Knockdown of β-cell mitogen-activated protein 4 kinase 4 prevented these effects. Glucagon-like peptide 1 protected β-cells against decreased proliferation and apoptosis evoked by TMs, while interleukin-1 receptor antagonist only prevented the latter. CONCLUSIONS Taken together, these data suggest a possible new route of communication between skeletal muscle and β-cells that is modulated by insulin resistance and could contribute to normal β-cell functional mass in healthy subjects, as well as the decrease seen in type 2 diabetes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|