Increased carnitine palmitoyl transferase 1 expression and decreased sterol regulatory element–binding protein 1c expression are associated with reduced intramuscular triglyceride accumulation after insulin therapy in high-fat–diet and streptozotocin-induced diabetic rats

• Published in: Metabolism, clinical and experimental Vol. 58; no. 6; pp. 779 - 786
• Main Authors: Bi, Yan, Cai, Mengyin, Liang, Hua, Sun, Weiping, Li, Xiubin, Wang, Chunxia, Zhu, Yanhua, Chen, Xiang, Li, Ming, Weng, Jianping
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-06-2009; Elsevier
• Subjects: Animals; Biological and medical sciences; Carnitine O-Palmitoyltransferase - analysis; Carnitine O-Palmitoyltransferase - drug effects; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Diabetes. Impaired glucose tolerance; Dietary Fats; Endocrine pancreas. Apud cells (diseases); Endocrinology & Metabolism; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Insulin - pharmacology; Insulin - therapeutic use; Lipid Metabolism - drug effects; Lipoprotein Lipase - analysis; Lipoprotein Lipase - metabolism; Medical sciences; Muscle, Skeletal - metabolism; Rats; Rats, Sprague-Dawley; Sterol Regulatory Element Binding Protein 1 - analysis; Sterol Regulatory Element Binding Protein 1 - drug effects; Streptozocin; Triglycerides - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Endocrinopathy; Antineoplastic agent; Pancreatic hormone; Rat; Lipids; Accumulation; Binding protein; Association; Streptozotocin; Enzyme; Diabetes mellitus; Transferases; Rodentia; Gene expression; Triglyceride; Insulin; Feeding; Carnitine; Vertebrata; Antibiotic; Mammalia; Treatment; Diet; Aminoacid; Animal; Fat; Endocrinology; Sterol
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2009.01.011

Abstract We previously reported that early insulin treatment reduced intramuscular triglyceride content in type 2 diabetes mellitus Sprague-Dawley rats; the underlying mechanisms are, however, not completely understood. Here we investigated the regulation of insulin on molecular expressions involved in lipid metabolism pathways in skeletal muscle of high-fat–diet and streptozotocin-induced diabetic Sprague-Dawley rats. Neutral protamine Hagedorn insulin and gliclazide were initiated at the third day after streptozotocin injection and lasted for 3 weeks. Compared with normal rats, untreated diabetic rats had a 30% and 61% increase in lipoprotein lipase protein expression and activity, which were decreased by insulin and gliclazide ( P < .05). Fatty acid translocase protein was down-regulated by 45% in untreated diabetic rats, which was up-regulated by 31% and 26% with insulin and gliclazide, respectively ( P < .05). Insulin failed to affect fatty acid transport protein 1 and fatty acid binding protein expressions. Carnitine palmitoyl transferase 1 had a 47% decrease in untreated diabetic rats, which was normalized by insulin ( P < .05). Moreover, compared with normal rats, untreated diabetic rats had higher expressions of sterol regulatory element–binding protein 1c, tumor necrosis factor α , and Tyr705 phosphorylation of signal transducer and activator of transcription 3 levels, which all were down-regulated after insulin treatment. These results suggested that early insulin reduced intramuscular triglyceride levels in diabetic rats potentially through amelioration of lipid dysfunction and inhibition of lipid synthesis.