Overexpression of PACAP in transgenic mouse pancreatic [beta]-cells enhances insulin secretion and ameliorates streptozotocin-induced diabetes. .(pituitary adenylate cyclase-activating polypeptide)
Pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the vasoactive intestinal peptide/secretin/glucagon family, stimulates insulin secretion from islets in a glucose-dependent manner at femtomolar concentrations. To assess PACAP's pancreatic function in vivo, we generated tr...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2003-05, Vol.52 (5), p.1155 |
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| creator | Yamamoto, Kyohei Hashimoto, Hitoshi Tomimoto, Shuhei Shintani, Norihito Miyazaki, Jun-ichi Tashiro, Fumi Aihara, Hiroyuki Nammo, Takao Li, Ming Yamagata, Kazuya Miyagawa, Jun-ichiro Matsuzawa, Yuji Kawabata, Yuki Fukuyama, Yuji Koga, Kazumi Mori, Wakaba Tanaka, Kazuhiro Matsuda, Toshio Baba, Akemichi |
| description | Pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the vasoactive intestinal peptide/secretin/glucagon family, stimulates insulin secretion from islets in a glucose-dependent manner at femtomolar concentrations. To assess PACAP's pancreatic function in vivo, we generated transgenic mice overexpressing PACAP in the pancreas under the control of human insulin promoter. Northern blot and immunohistochemical analyses showed that PACAP is overexpressed in pancreatic islets, specifically in transgenic mice. Plasma glucose and glucagon levels during a glucose tolerance test were not different between PACAP transgenic mice and nontransgenic littermates. However, plasma insulin levels in transgenic mice were higher after glucose loading. Also, increases of streptozotocin-induced plasma glucose were attenuated in transgenic compared with nontransgenic mice. Notably, an increase in 5-bromo-2-deoxyuridine-positive [beta]-cells in the streptozotocin-treated transgenic mice was observed but without differences in the staining patterns by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Morphometric analysis revealed that total islet mass tends to increase in 12-month-old transgenic mice but showed no difference between 12-week-old transgenic and nontransgenic littermates. This is the first time that PACAP has been observed to play an important role in the proliferation of [beta]-cells. |
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To assess PACAP's pancreatic function in vivo, we generated transgenic mice overexpressing PACAP in the pancreas under the control of human insulin promoter. Northern blot and immunohistochemical analyses showed that PACAP is overexpressed in pancreatic islets, specifically in transgenic mice. Plasma glucose and glucagon levels during a glucose tolerance test were not different between PACAP transgenic mice and nontransgenic littermates. However, plasma insulin levels in transgenic mice were higher after glucose loading. Also, increases of streptozotocin-induced plasma glucose were attenuated in transgenic compared with nontransgenic mice. Notably, an increase in 5-bromo-2-deoxyuridine-positive [beta]-cells in the streptozotocin-treated transgenic mice was observed but without differences in the staining patterns by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Morphometric analysis revealed that total islet mass tends to increase in 12-month-old transgenic mice but showed no difference between 12-week-old transgenic and nontransgenic littermates. This is the first time that PACAP has been observed to play an important role in the proliferation of [beta]-cells.</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>New York: American Diabetes Association</publisher><subject>Cell growth ; Diabetes ; Diabetes mellitus ; Diabetes research ; Glucagon ; Glucose ; Insulin ; Kinases ; Nervous system ; Pancreas ; Pancreatic beta cells ; Physiological aspects ; Physiology ; Polypeptides ; Proteins ; Transgenic animals</subject><ispartof>Diabetes (New York, N.Y.), 2003-05, Vol.52 (5), p.1155</ispartof><rights>COPYRIGHT 2003 American Diabetes Association</rights><rights>Copyright American Diabetes Association May 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids></links><search><creatorcontrib>Yamamoto, Kyohei</creatorcontrib><creatorcontrib>Hashimoto, Hitoshi</creatorcontrib><creatorcontrib>Tomimoto, Shuhei</creatorcontrib><creatorcontrib>Shintani, Norihito</creatorcontrib><creatorcontrib>Miyazaki, Jun-ichi</creatorcontrib><creatorcontrib>Tashiro, Fumi</creatorcontrib><creatorcontrib>Aihara, Hiroyuki</creatorcontrib><creatorcontrib>Nammo, Takao</creatorcontrib><creatorcontrib>Li, Ming</creatorcontrib><creatorcontrib>Yamagata, Kazuya</creatorcontrib><creatorcontrib>Miyagawa, Jun-ichiro</creatorcontrib><creatorcontrib>Matsuzawa, Yuji</creatorcontrib><creatorcontrib>Kawabata, Yuki</creatorcontrib><creatorcontrib>Fukuyama, Yuji</creatorcontrib><creatorcontrib>Koga, Kazumi</creatorcontrib><creatorcontrib>Mori, Wakaba</creatorcontrib><creatorcontrib>Tanaka, Kazuhiro</creatorcontrib><creatorcontrib>Matsuda, Toshio</creatorcontrib><creatorcontrib>Baba, Akemichi</creatorcontrib><title>Overexpression of PACAP in transgenic mouse pancreatic [beta]-cells enhances insulin secretion and ameliorates streptozotocin-induced diabetes. .(pituitary adenylate cyclase-activating polypeptide)</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the vasoactive intestinal peptide/secretin/glucagon family, stimulates insulin secretion from islets in a glucose-dependent manner at femtomolar concentrations. To assess PACAP's pancreatic function in vivo, we generated transgenic mice overexpressing PACAP in the pancreas under the control of human insulin promoter. Northern blot and immunohistochemical analyses showed that PACAP is overexpressed in pancreatic islets, specifically in transgenic mice. Plasma glucose and glucagon levels during a glucose tolerance test were not different between PACAP transgenic mice and nontransgenic littermates. However, plasma insulin levels in transgenic mice were higher after glucose loading. Also, increases of streptozotocin-induced plasma glucose were attenuated in transgenic compared with nontransgenic mice. Notably, an increase in 5-bromo-2-deoxyuridine-positive [beta]-cells in the streptozotocin-treated transgenic mice was observed but without differences in the staining patterns by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Morphometric analysis revealed that total islet mass tends to increase in 12-month-old transgenic mice but showed no difference between 12-week-old transgenic and nontransgenic littermates. This is the first time that PACAP has been observed to play an important role in the proliferation of [beta]-cells.</description><subject>Cell growth</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes research</subject><subject>Glucagon</subject><subject>Glucose</subject><subject>Insulin</subject><subject>Kinases</subject><subject>Nervous system</subject><subject>Pancreas</subject><subject>Pancreatic beta cells</subject><subject>Physiological aspects</subject><subject>Physiology</subject><subject>Polypeptides</subject><subject>Proteins</subject><subject>Transgenic 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N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamamoto, Kyohei</au><au>Hashimoto, Hitoshi</au><au>Tomimoto, Shuhei</au><au>Shintani, Norihito</au><au>Miyazaki, Jun-ichi</au><au>Tashiro, Fumi</au><au>Aihara, Hiroyuki</au><au>Nammo, Takao</au><au>Li, Ming</au><au>Yamagata, Kazuya</au><au>Miyagawa, Jun-ichiro</au><au>Matsuzawa, Yuji</au><au>Kawabata, Yuki</au><au>Fukuyama, Yuji</au><au>Koga, Kazumi</au><au>Mori, Wakaba</au><au>Tanaka, Kazuhiro</au><au>Matsuda, Toshio</au><au>Baba, Akemichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of PACAP in transgenic mouse pancreatic [beta]-cells enhances insulin secretion and ameliorates streptozotocin-induced diabetes. .(pituitary adenylate cyclase-activating polypeptide)</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2003-05-01</date><risdate>2003</risdate><volume>52</volume><issue>5</issue><spage>1155</spage><pages>1155-</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><abstract>Pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the vasoactive intestinal peptide/secretin/glucagon family, stimulates insulin secretion from islets in a glucose-dependent manner at femtomolar concentrations. To assess PACAP's pancreatic function in vivo, we generated transgenic mice overexpressing PACAP in the pancreas under the control of human insulin promoter. Northern blot and immunohistochemical analyses showed that PACAP is overexpressed in pancreatic islets, specifically in transgenic mice. Plasma glucose and glucagon levels during a glucose tolerance test were not different between PACAP transgenic mice and nontransgenic littermates. However, plasma insulin levels in transgenic mice were higher after glucose loading. Also, increases of streptozotocin-induced plasma glucose were attenuated in transgenic compared with nontransgenic mice. Notably, an increase in 5-bromo-2-deoxyuridine-positive [beta]-cells in the streptozotocin-treated transgenic mice was observed but without differences in the staining patterns by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Morphometric analysis revealed that total islet mass tends to increase in 12-month-old transgenic mice but showed no difference between 12-week-old transgenic and nontransgenic littermates. This is the first time that PACAP has been observed to play an important role in the proliferation of [beta]-cells.</abstract><cop>New York</cop><pub>American Diabetes Association</pub></addata></record> |
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| subjects | Cell growth Diabetes Diabetes mellitus Diabetes research Glucagon Glucose Insulin Kinases Nervous system Pancreas Pancreatic beta cells Physiological aspects Physiology Polypeptides Proteins Transgenic animals |
| title | Overexpression of PACAP in transgenic mouse pancreatic [beta]-cells enhances insulin secretion and ameliorates streptozotocin-induced diabetes. .(pituitary adenylate cyclase-activating polypeptide) |
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