Involvement of cyclooxygenase 2 and prostagladin E(2) in the effects of insulin on gastric emptying in male rats.
Delayed gastric emptying in patients with both type 1 and type 2 diabetes mellitus (DM) occurs in approximately 50% of these patients. However, the role and the action mechanism of insulin on gastrointestinal (GI) motility are still unclear. The purpose of the present study was to investigate the involvement of cyclooxygenase-2 (COX-2) and prostaglandin E(2) in the effects of insulin on gastric emptying in male rats. The normal and streptozotocin (STZ)-pretreated rats were injected intraperitoneally with or without insulin, atropine and specific muscarinic receptor antagonists before examination of measurement of gastric emptying, spontaneous contractile activity of smooth muscle strips, plasma cholecystokinin (CCK), and prostaglandin E(2) (PGE(2)) analysis. Protein expression of COX-2 and insulin receptors (IRs) were analyzed by the technique of western blot. Acute different doses of insulin accelerated gastric emptying. Atropine interrupted the insulin effect on gastric emptying, and muscarnic M1/M3 receptor antagonists interrupted the insulin-reversed gastric emptying in normal and DM rats. Besides, we observed the expression of (IRs) in GI and found that IR was changed under the insulin and DM treatment, and was also different between STZ-pretreated rats and hyperglycemic rats. Expression of COX-2 in stomach was decreased in DM rats but restored by insulin. The COX inhibitor, indomethacin, decreased the gastric emptying which was induced or reversed by insulin in normal and DM rats, respectively. PGE(2) production in stomach corresponded to the COX-2 expression. The contraction of GI smooth muscle stimulated by PGE(2) was increased in insulin-pretreated normal and DM rats. We conclude that insulin changed the expression of IRs in stomach in DM rats. The delayed GI motility in diabetes was at least in part due to the COX-2 and PGE(2) pathway which associated with decreasing COX-2 and diminishing PGE(2) production in stomach. The attenuation of PGE(2) production was employed for the index of the reduction of smooth muscle contraction in stomach in diabetes. Insulin stimulated the smooth muscle contraction through the IRs and COX-2 expression plus PGE(2) production in rat stomach as well as reversed the delayed gastric emptying via the nervous actions of muscarinic M1 and M3 receptors in DM rats.
Huang
W -J
W-
Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan R.O.C.
Hung
C -R
C-
Chen
M -C
M-
Wang
J -R
J-
Doong
M -L
M-
Wang
C -K
C-
Hung
C -T
C-
Wang
P S
PS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D015232:Dinoprostone / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D005746:Gastric Emptying / Q000187:drug effects*; D005753:Gastric Mucosa / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology* / Q000502:physiology / Q000627:therapeutic use; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism; D043643:Receptor, Muscarinic M1 / Q000378:metabolism; D043587:Receptor, Muscarinic M3 / Q000378:metabolism; D013270:Stomach / Q000187:drug effects / Q000201:enzymology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; D051546:Cyclooxygenase 2; D011972:Receptor, Insulin; D015232:Dinoprostone