Myosin light chain kinase is involved in the mechanism of gastrointestinal dysfunction in diabetic rats.
BACKGROUND
It is well established that smooth muscle contractility is regulated by an elevation of cytosolic Ca(2+) via myosin light chain phosphorylation, which is activated by myosin light chain kinase (MLCK). Recently, MLCK has been demonstrated to play an important role in smooth muscle contraction and normal gastrointestinal motility.


OBJECTIVE
The aim of our study is to investigate whether MLCK is involved in the mechanism of gastrointestinal dysfunction and the ameliorating effects of insulin on gastrointestinal dysfunction in diabetic rats.


METHODS
A diabetic rat model was established by an intravenous injection with streptozotocin. Rats were randomized into three groups: control group, diabetic group, and insulin-treated group. The gastrointestinal functions were assessed in terms of gastric emptying and intestinal transit. The expression of MLCK in the pylorus and ileum of the three groups was determined by real-time polymerase chain reaction (PCR) and Western blot methods.


RESULTS
The diabetic group exhibited a significant delay in gastric emptying and intestinal transit than the control group. Insulin treatment significantly ameliorated the gastric emptying and intestinal transit in diabetic rats. The expression levels of MLCK in the pylorus and ileum of the diabetic group were both significantly decreased compared with the control group, and the changes of MLCK expression in these tissues of diabetic rats were partially reversed after treatment with insulin.


CONCLUSIONS
Decreased expression of MLCK in gastrointestinal tissues could be a possible cause for gastrointestinal dysfunction. Insulin may partly ameliorate gastrointestinal dysfunction by restoring the expression of MLCK.
Department of Metabolism, General Hospital, Tianjin Medical University, 154 Anshan Street, Heping District, Tianjin 300052, People’s Republic of China.
Wenchao
W
Hu
Ping
P
Feng
D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D005746:Gastric Emptying / Q000187:drug effects / Q000235:genetics; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007082:Ileum / Q000201:enzymology / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000235:genetics; D009130:Muscle, Smooth / Q000201:enzymology / Q000503:physiopathology; D018994:Myosin Light Chains / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000235:genetics*; D010766:Phosphorylation; D011708:Pylorus / Q000201:enzymology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013311:Streptozocin
D007328:Insulin; D018994:Myosin Light Chains; D013311:Streptozocin; D009219:Myosin-Light-Chain Kinase