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.
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 alpha, and Tyr(705) 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.
Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, PR China.
Yan
Y
Bi
Mengyin
M
Cai
Hua
H
Liang
Weiping
W
Sun
Xiubin
X
Li
Chunxia
C
Wang
Yanhua
Y
Zhu
Xiang
X
Chen
Ming
M
Li
Jianping
J
Weng
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000032:analysis* / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D004041:Dietary Fats; D005786:Gene Expression Regulation / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology* / Q000627:therapeutic use; D050356:Lipid Metabolism / Q000187:drug effects; D008071:Lipoprotein Lipase / Q000032:analysis / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051780:Sterol Regulatory Element Binding Protein 1 / Q000032:analysis* / Q000187:drug effects; D013311:Streptozocin; D014280:Triglycerides / Q000378:metabolism*
D004041:Dietary Fats; D007328:Insulin; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D013311:Streptozocin; D002334:Carnitine O-Palmitoyltransferase; D008071:Lipoprotein Lipase