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.
Bi
Yan
Y
Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, PR China.
Cai
Mengyin
M
Liang
Hua
H
Sun
Weiping
W
Li
Xiubin
X
Wang
Chunxia
C
Zhu
Yanhua
Y
Chen
Xiang
X
Li
Ming
M
Weng
Jianping
J
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