{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T01:25:47Z","timestamp":1776302747066,"version":"3.50.1"},"reference-count":54,"publisher":"American Diabetes Association","issue":"7","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,7,1]]},"abstract":"<jats:p>Type 2 diabetes is characterized by a relative \u03b2-cell deficit as a result of increased \u03b2-cell apoptosis and islet amyloid derived from the \u03b2-cell peptide islet amyloid polypeptide (IAPP). Human IAPP (h-IAPP) but not mouse IAPP (m-IAPP) induces apoptosis when applied to cells in culture, a property that depends on the propensity of h-IAPP to oligomerize. Since \u03b2-cell mass is regulated, the question arises as to why it is not adaptively increased in response to insulin resistance and hyperglycemia in type 2 diabetes. This adaptation might fail if dividing \u03b2-cells preferentially underwent apoptosis. We tested the hypothesis that \u03b2-cells are preferentially vulnerable to h-IAPP-induced apoptosis. We established a microculture environment to perform time-lapse video microscopy (TLVM) and studied \u03b2-cells (RIN) and HeLa cells undergoing replication or apoptosis. Sequential images (every 10 min for 36 h in RIN or 24 h in HeLa cells) of cells in vivo were analyzed, and each mitotic and apoptotic event was documented. Freshly dissolved h-IAPP caused a dose-dependent increased rate of apoptosis (P &amp;lt; 0.0001) in both cell types. At low and medium levels of toxicity, cells that had previously undergone mitosis were more vulnerable to h-IAPP-induced apoptosis than nondividing cells (P &amp;lt; 0.05). In the first 3 h after mitosis (full cell cycle length 26 \u00b1 0.6 h), \u03b2-cells were particularly susceptible to h-IAPP-induced apoptosis (P &amp;lt; 0.05). Neither m-IAPP nor mature amyloid aggregates of h-IAPP were cytotoxic (P = 0.49). To corroborate these cell culture studies, we examined sections of human pancreatic tissue (five cases of type 2 diabetes) and human islets incubated for 48 h \u00b1 h-IAPP. Both were stained for apoptosis with the transferase-mediated dUTP nick-end labeling method and analyzed for the presence of paired apoptotic cells anticipated in the event of postmitotic apoptosis. In human pancreatic tissue 26 \u00b1 5% (single plane of examination) and in human islets incubated with h-IAPP 44 \u00b1 4% of apoptotic islet cells were paired. In conclusion, replicating \u03b2-cells are preferentially vulnerable to h-IAPP-induced apoptosis in cell culture. Postmitotic apoptosis was also documented in humans with type 2 diabetes and in human islet tissue. We postulate that \u03b2-cell deficiency in type 2 diabetes may result in part from failure to adaptively increase \u03b2-cell mass due to increased vulnerability of replicating \u03b2-cells to undergo apoptosis. If this postulate is correct, then inhibition of apoptosis should allow recovery of \u03b2-cell mass in type 2 diabetes.<\/jats:p>","DOI":"10.2337\/diabetes.52.7.1701","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"1701-1708","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":91,"title":["Replication Increases \u03b2-Cell Vulnerability to Human Islet Amyloid Polypeptide-Induced Apoptosis"],"prefix":"10.2337","volume":"52","author":[{"given":"Robert A.","family":"Ritzel","sequence":"first","affiliation":[{"name":"From the Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter C.","family":"Butler","sequence":"additional","affiliation":[{"name":"From the Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031209373076300_R1","doi-asserted-by":"crossref","unstructured":"Kloppel G, Lohr M, Habich K, Oberholzer M, Heitz PU: Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited. 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