Shikonin increases glucose uptake in skeletal muscle cells and improves plasma glucose levels in diabetic Goto-Kakizaki rats
| Autor: | Mona Wilcke, Claes-Göran Östenson, Robert I. Csikasz, Nodi Dehvari, Anette I. Öberg, Dana S. Hutchinson, Tore Bengtsson, Kamal Yassin, Irina G. Shabalina |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Blood Glucose
Male Anatomy and Physiology medicine.medical_treatment Glucose uptake Muscle Fibers Skeletal lcsh:Medicine Type 2 diabetes Mitochondrion AMP-Activated Protein Kinases 0302 clinical medicine Adenosine Triphosphate Glucose homeostasis Insulin Phosphorylation lcsh:Science 0303 health sciences Multidisciplinary Glucose Transporter Type 4 Chemistry food and beverages Adenosine Diphosphate Protein Transport medicine.anatomical_structure 030220 oncology & carcinogenesis Medicine Research Article medicine.medical_specialty Drugs and Devices Endocrine System Cell Line Diabetes Mellitus Experimental 03 medical and health sciences Oxygen Consumption Complementary and Alternative Medicine Diabetes mellitus Internal medicine medicine Animals Muscle Skeletal Biology 030304 developmental biology Diabetic Endocrinology Muscle Cells Endocrine Physiology fungi lcsh:R Skeletal muscle medicine.disease Rats Endocrinology Cell culture Metabolic Disorders Calcium lcsh:Q Proto-Oncogene Proteins c-akt Naphthoquinones |
| Zdroj: | PLoS ONE, Vol 6, Iss 7, p e22510 (2011) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | BACKGROUND: There is considerable interest in identifying compounds that can improve glucose homeostasis. Skeletal muscle, due to its large mass, is the principal organ for glucose disposal in the body and we have investigated here if shikonin, a naphthoquinone derived from the Chinese plant Lithospermum erythrorhizon, increases glucose uptake in skeletal muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: Shikonin increases glucose uptake in L6 skeletal muscle myotubes, but does not phosphorylate Akt, indicating that in skeletal muscle cells its effect is medaited via a pathway distinct from that used for insulin-stimulated uptake. Furthermore we find no evidence for the involvement of AMP-activated protein kinase in shikonin induced glucose uptake. Shikonin increases the intracellular levels of calcium in these cells and this increase is necessary for shikonin-mediated glucose uptake. Furthermore, we found that shikonin stimulated the translocation of GLUT4 from intracellular vesicles to the cell surface in L6 myoblasts. The beneficial effect of shikonin on glucose uptake was investigated in vivo by measuring plasma glucose levels and insulin sensitivity in spontaneously diabetic Goto-Kakizaki rats. Treatment with shikonin (10 mg/kg intraperitoneally) once daily for 4 days significantly decreased plasma glucose levels. In an insulin sensitivity test (s.c. injection of 0.5 U/kg insulin), plasma glucose levels were significantly lower in the shikonin-treated rats. In conclusion, shikonin increases glucose uptake in muscle cells via an insulin-independent pathway dependent on calcium. CONCLUSIONS/SIGNIFICANCE: Shikonin increases glucose uptake in skeletal muscle cells via an insulin-independent pathway dependent on calcium. The beneficial effects of shikonin on glucose metabolism, both in vitro and in vivo, show that the compound possesses properties that make it of considerable interest for developing novel treatment of type 2 diabetes. |
| Databáze: | OpenAIRE |
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