{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T19:04:25Z","timestamp":1768763065787,"version":"3.49.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,11,28]],"date-time":"2006-11-28T00:00:00Z","timestamp":1164672000000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:p><jats:bold><jats:sc>Abstract:\u2002<\/jats:sc><\/jats:bold>  <jats:bold>Diabetes mellitus (DM) is a major health problem at present affecting about 180 million people worldwide. DM is associated with many metabolic abnormalities in the body including the indigestion of carbohydrates leading to malnutrition and weight loss. In this article we investigate the cellular and molecular mechanisms of exocrine pancreatic insufficiency in streptozotocin (STZ, 60 mg kg<jats:sup>\u22121<\/jats:sup>, i.p.)\u2010induced DM in male rats compared to healthy age\u2010matched controls. Either electrical field stimulation (EFS) or cholecystokinin octapeptide (CCK\u20108, 10<jats:sup>\u22128<\/jats:sup> M) can elicit large and significant (<jats:italic>P<\/jats:italic> &lt; 0.05) increases in amylase output from pancreatic segments compared to basal secretion. Insulin (10<jats:sup>\u22126<\/jats:sup> M) alone has no significant effect on amylase output compared to basal but it enhanced the secretory responses to either EFS or CCK\u20108. When rats were rendered diabetic with STZ, either EFS or CCK\u20108\u2010evoked amylase output was significantly (<jats:italic>P<\/jats:italic> &lt; 0.01) decreased compared to the responses obtained with either EFS or CCK\u20108 alone in healthy age\u2010matched control pancreas. In addition, CCK\u20108 can elicit large dose\u2010dependent release of amylase in age\u2010matched control and diabetic acinar cells with significantly (<jats:italic>P<\/jats:italic> &lt; 0.05) reduced responses in diabetic acinar cells. CCK\u20108 evoked a large rapid increase in peak cytosolic free calcium concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>c<\/jats:sub>) followed by a decrease to a plateau phase in age\u2010matched control fura\u20102\u2010loaded pancreatic acinar cells. These responses were significantly (<jats:italic>P<\/jats:italic> &lt; 0.05) decreased in STZ\u2010induced diabetic acinar cells. In the presence of 10<jats:sup>\u22126<\/jats:sup> M insulin, CCK\u20108 evoked a much larger increase in the Ca<jats:sup>2+<\/jats:sup> transient compared to the response obtained with CCK\u20108 alone. These effects were significantly (<jats:italic>P<\/jats:italic> &lt; 0.01) inhibited in STZ\u2010induced diabetic acinar cells. Similarly, in zero extracellular Ca<jats:sup>2+<\/jats:sup>[Ca<jats:sup>2+<\/jats:sup>]\u0109, the CCK\u20108\u2010evoked [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>c<\/jats:sub> was significantly (<jats:italic>P<\/jats:italic> &lt; 0.05) reduced in both diabetic and age\u2010matched control acinar cells, but with more pronounced reduction in diabetic acinar cells. CCK<jats:sub>A<\/jats:sub> receptor mRNA levels remained unchanged in diabetic rat acinar cells compared to age\u2010matched healthy control. In contrast, amylase mRNA was significantly (<jats:italic>P<\/jats:italic> &lt; 0.05) reduced in diabetic acinar cells compared to control. The results indicate that reduced amylase secretion in response to either EFS or CCK\u20108 in the diabetic pancreas may be due to reduced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>c<\/jats:sub> and gene expression for amylase and not to the gene expression of CCK<jats:sub>A<\/jats:sub> receptor in pancreatic acinar cells.<\/jats:bold> <\/jats:p>","DOI":"10.1196\/annals.1372.038","type":"journal-article","created":{"date-parts":[[2006,12,6]],"date-time":"2006-12-06T20:08:44Z","timestamp":1165435724000},"page":"71-88","source":"Crossref","is-referenced-by-count":36,"title":["Mechanism of Exocrine Pancreatic Insufficiency in Streptozotocin\u2010Induced Type 1 Diabetes Mellitus"],"prefix":"10.1111","volume":"1084","author":[{"given":"REKHA","family":"PATEL","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"AMIL","family":"SHERVINGTON","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JOSE A.","family":"PARIENTE","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MARIA A.","family":"MARTINEZ\u2010BURGOS","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"GINES M.","family":"SALIDO","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ERNEST","family":"ADEGHATE","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JAIPAUL","family":"SINGH","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,11,28]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"789","volume-title":"The Exocrine Pancreas: Biology, Pathology and Disease","author":"Williams J.A.","year":"1993"},{"key":"e_1_2_6_3_2","first-page":"197","volume-title":"Neural Regulation in the Vertebrate Endocrine System: neuroendocrine Regulation","author":"Yago M.D.","year":"1998"},{"key":"e_1_2_6_4_2","first-page":"47","article-title":"Interactions of islet peptides with cholecystoknin\u2010octapeptide in normal and diabetic pancreas","volume":"6","author":"Patel R.","year":"2004","journal-title":"Curr. 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