Involvement of Cyclooxygenase 2 and Prostaglandin E2 in the Effects of Insulin on Gastriointestinal Motility in Male Rats
博士 === 國立陽明大學 === 生理學研究所 === 97 === 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 pre...
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ndltd-TW-097YM0051160032019-05-15T20:07:01Z http://ndltd.ncl.edu.tw/handle/3zsmw8 Involvement of Cyclooxygenase 2 and Prostaglandin E2 in the Effects of Insulin on Gastriointestinal Motility in Male Rats 第二型環氧化酶及前列腺素參與胰島素對雄性大鼠胃腸運動之效應 Wei-Ju Huang 黃薇如 博士 國立陽明大學 生理學研究所 97 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) in diabetes inflammation, and muscarinic cholinergic receptor in diabetes neuropathy about the effects of insulin on GI motility 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, and prostaglandin E2 (PGE2) analysis. COX-2 expression and insulin receptor (IR) were analyzed by the technique of western blot. Our results showed that the GI motility was different between the early stage and the later period of DM. The COX-2 expression decreased after 1 week STZ-induced diabetes but was reversed several days later. Administration of insulin accelerated GI motility as well as the IR and COX-2 expression. In the early stage of DM, we observed the IR expression 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. PGE2 production in stomach corresponded to the COX-2 expression. The contraction of GI smooth muscle stimulated by PGE2 was increased in insulin-pretreated normal and DM rats. On the other hand, 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. We conclude that the side-effects of GI motility were associated with the COX-2 expression during diabetic inflammation. The GI smooth muscle contraction was affected via the COX-2 activation and PGE2 production. Besides, the delayed GI motility in early stage of diabetes was associated with the muscarinic cholinergic system in diabetic neuropathy. Insulin improved the delayed GI motility in the early stage of DM through the IR and COX-2 expression plus PGE2 production of COX-2 and PGE2 pathway in stomach and intestine as well as reversed the delayed gastric emptying via the nervous actions of muscarinic M1 and M3 receptors in DM rats. Paulus S. Wang Ming-Luen Doong 王錫崗 董明倫 2009 學位論文 ; thesis 255 zh-TW |
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博士 === 國立陽明大學 === 生理學研究所 === 97 === 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) in diabetes inflammation, and muscarinic cholinergic receptor in diabetes neuropathy about the effects of insulin on GI motility 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, and prostaglandin E2 (PGE2) analysis. COX-2 expression and insulin receptor (IR) were analyzed by the technique of western blot. Our results showed that the GI motility was different between the early stage and the later period of DM. The COX-2 expression decreased after 1 week STZ-induced diabetes but was reversed several days later. Administration of insulin accelerated GI motility as well as the IR and COX-2 expression. In the early stage of DM, we observed the IR expression 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. PGE2 production in stomach corresponded to the COX-2 expression. The contraction of GI smooth muscle stimulated by PGE2 was increased in insulin-pretreated normal and DM rats. On the other hand, 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. We conclude that the side-effects of GI motility were associated with the COX-2 expression during diabetic inflammation. The GI smooth muscle contraction was affected via the COX-2 activation and PGE2 production. Besides, the delayed GI motility in early stage of diabetes was associated with the muscarinic cholinergic system in diabetic neuropathy. Insulin improved the delayed GI motility in the early stage of DM through the IR and COX-2 expression plus PGE2 production of COX-2 and PGE2 pathway in stomach and intestine as well as reversed the delayed gastric emptying via the nervous actions of muscarinic M1 and M3 receptors in DM rats.
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author2 |
Paulus S. Wang |
author_facet |
Paulus S. Wang Wei-Ju Huang 黃薇如 |
author |
Wei-Ju Huang 黃薇如 |
spellingShingle |
Wei-Ju Huang 黃薇如 Involvement of Cyclooxygenase 2 and Prostaglandin E2 in the Effects of Insulin on Gastriointestinal Motility in Male Rats |
author_sort |
Wei-Ju Huang |
title |
Involvement of Cyclooxygenase 2 and Prostaglandin E2 in the Effects of Insulin on Gastriointestinal Motility in Male Rats |
title_short |
Involvement of Cyclooxygenase 2 and Prostaglandin E2 in the Effects of Insulin on Gastriointestinal Motility in Male Rats |
title_full |
Involvement of Cyclooxygenase 2 and Prostaglandin E2 in the Effects of Insulin on Gastriointestinal Motility in Male Rats |
title_fullStr |
Involvement of Cyclooxygenase 2 and Prostaglandin E2 in the Effects of Insulin on Gastriointestinal Motility in Male Rats |
title_full_unstemmed |
Involvement of Cyclooxygenase 2 and Prostaglandin E2 in the Effects of Insulin on Gastriointestinal Motility in Male Rats |
title_sort |
involvement of cyclooxygenase 2 and prostaglandin e2 in the effects of insulin on gastriointestinal motility in male rats |
publishDate |
2009 |
url |
http://ndltd.ncl.edu.tw/handle/3zsmw8 |
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