{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T05:47:45Z","timestamp":1771048065706,"version":"3.50.1"},"reference-count":49,"publisher":"American Diabetes Association","issue":"2","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,2,1]]},"abstract":"<jats:p>OBJECTIVE\u2014The Cohen diabetes\u2013sensitive rat develops postprandial hyperglycemia when fed a high-sucrose, copper-poor diet, whereas the Cohen diabetes\u2013resistant rat maintains normoglycemia. The pathophysiological basis of diabetes was studied in the Cohen diabetic rat centering on the interplay between the exocrine and endocrine compartments of the pancreas.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014Studies used male Cohen diabetes\u2013sensitive and Cohen diabetes\u2013resistant rats fed 1-month high-sucrose, copper-poor diet. Serum insulin and glucose levels were measured during glucose and insulin tolerance tests. The pancreas was evaluated for weight, insulin content, macrophage, and fat infiltration. Glucose-stimulated insulin secretion (GSIS) was determined in isolated perfused pancreas and in islets.<\/jats:p>\n               <jats:p>RESULTS\u2014Hyperglycemic Cohen diabetes\u2013sensitive rats exhibited reduced pancreatic weight with lipid deposits and interleukin-1\u03b2\u2013positive macrophage infiltration in the exocrine pancreas. Islet morphology was preserved, and total pancreatic insulin content did not differ from that of Cohen diabetes\u2013resistant rats. Lipids did not accumulate in skeletal muscle, nor was insulin resistance observed in hyperglycemic Cohen diabetes\u2013sensitive rats. Intravenous glucose-tolerance test revealed markedly elevated glucose levels associated with diminished insulin output. Insulin release was induced in vivo by the non-nutrient secretagogues arginine and tolbutamide, suggesting a selective unresponsiveness to glucose. Decreased GSIS was observed in the isolated perfused pancreas of the hyperglycemic Cohen diabetes\u2013sensitive rat, whereas islets isolated from these rats exhibited glucose-dependent insulin secretion and proinsulin biosynthesis.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014The association of the in vivo insulin secretory defect with lipid accumulation and activated macrophage infiltration in the exocrine pancreas suggests that changes in the islet microenvironment are the culprit in the insulin secretory malfunction observed in vivo.<\/jats:p>","DOI":"10.2337\/db07-0520","type":"journal-article","created":{"date-parts":[[2007,11,1]],"date-time":"2007-11-01T00:54:28Z","timestamp":1193878468000},"page":"279-287","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":49,"title":["Impaired Glucose-Stimulated Insulin Secretion Is Coupled With Exocrine Pancreatic Lesions in the Cohen Diabetic Rat"],"prefix":"10.2337","volume":"57","author":[{"given":"Sarah","family":"Weksler-Zangen","sequence":"first","affiliation":[{"name":"The Diabetes Unit, Department of Internal Medicine and The Hadassah Diabetes Center, Hadassah-Hebrew University Medical Center, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Itamar","family":"Raz","sequence":"additional","affiliation":[{"name":"The Diabetes Unit, Department of Internal Medicine and The Hadassah Diabetes Center, Hadassah-Hebrew University Medical Center, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sigurd","family":"Lenzen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Jo\u0308rns","sequence":"additional","affiliation":[{"name":"Centre of Anatomy, Hannover Medical School, Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shira","family":"Ehrenfeld","sequence":"additional","affiliation":[{"name":"The Diabetes Unit, Department of Internal Medicine and The Hadassah Diabetes Center, Hadassah-Hebrew University Medical Center, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gail","family":"Amir","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrei","family":"Oprescu","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Service, Department of Internal Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoram","family":"Yagil","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Medicine and Israeli Rat Genome Center, Faculty of Health Sciences, Barzilai Medical Center, Campus of the Ben-Gurion University, Ashkelon, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chana","family":"Yagil","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Medicine and Israeli Rat Genome Center, Faculty of Health Sciences, Barzilai Medical Center, Campus of the Ben-Gurion University, Ashkelon, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H.","family":"Zangen","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nurit","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Service, Department of Internal Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031208005700700_R1","doi-asserted-by":"crossref","unstructured":"Pimenta W, Korytkowski M, Mitrakou A, Jenssen T, Yki-Jarvinen H, Evron W, Dailey G, Gerich J: Pancreatic beta-cell dysfunction as the primary genetic lesion in NIDDM: evidence from studies in normal glucose-tolerant individuals with a first-degree NIDDM relative. 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