{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:14:49Z","timestamp":1791274489318,"version":"4.1.0"},"reference-count":49,"publisher":"American Diabetes Association","issue":"1","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"<jats:p>Chromogranin A knockout (Chga-KO) mice exhibit enhanced insulin sensitivity despite obesity. Here, we probed the role of the chromogranin A\u2013derived peptide pancreastatin (PST: CHGA273\u2013301) by investigating the effect of diet-induced obesity (DIO) on insulin sensitivity of these mice. We found that on a high-fat diet (HFD), Chga-KO mice (KO-DIO) remain more insulin sensitive than wild-type DIO (WT-DIO) mice. Concomitant with this phenotype is enhanced Akt and AMPK signaling in muscle and white adipose tissue (WAT) as well as increased FoxO1 phosphorylation and expression of mature Srebp-1c in liver and downregulation of the hepatic gluconeogenic genes, Pepck and G6pase. KO-DIO mice also exhibited downregulation of cytokines and proinflammatory genes and upregulation of anti-inflammatory genes in WAT, and peritoneal macrophages from KO mice displayed similarly reduced proinflammatory gene expression. The insulin-sensitive, anti-inflammatory phenotype of KO-DIO mice is masked by supplementing PST. Conversely, a PST variant peptide PSTv1 (PST-N\u03943: CHGA276\u2013301), lacking PST activity, simulated the KO phenotype by sensitizing WT-DIO mice to insulin. In summary, the reduced inflammation due to PST deficiency prevented the development of insulin resistance in KO-DIO mice. Thus, obesity manifests insulin resistance only in the presence of PST, and in its absence obesity is dissociated from insulin resistance.<\/jats:p>","DOI":"10.2337\/db13-1747","type":"journal-article","created":{"date-parts":[[2014,7,22]],"date-time":"2014-07-22T01:32:56Z","timestamp":1405992776000},"page":"104-116","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":68,"title":["Pancreastatin-Dependent Inflammatory Signaling Mediates Obesity-Induced Insulin Resistance"],"prefix":"10.2337","volume":"64","author":[{"given":"Gautam K.","family":"Bandyopadhyay","sequence":"first","affiliation":[{"name":"VA San Diego Healthcare System, San Diego, CA"},{"name":"Department of Medicine, University of California, San Diego, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minh","family":"Lu","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ennio","family":"Avolio","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawed A.","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaur R.","family":"Gayen","sequence":"additional","affiliation":[{"name":"Central Drug Research Institute, Lucknow, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Wollam","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine U.","family":"Vu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nai-Wen","family":"Chi","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System, San Diego, CA"},{"name":"Department of Medicine, University of California, San Diego, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel T.","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System, San Diego, CA"},{"name":"Department of Medicine, University of California, San Diego, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushil K.","family":"Mahata","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System, San Diego, CA"},{"name":"Department of Medicine, University of California, San Diego, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2014,7,21]]},"reference":[{"key":"2022031223042580500_B1","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/0306-4522(92)90222-N","article-title":"The chromogranins A and B: the first 25 years and future perspectives","volume":"49","author":"Winkler","year":"1992","journal-title":"Neuroscience"},{"key":"2022031223042580500_B2","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1056\/NEJMra021405","article-title":"The chromogranin-secretogranin family","volume":"348","author":"Taupenot","year":"2003","journal-title":"N Engl J Med"},{"key":"2022031223042580500_B3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/j.1748-1716.2007.01806.x","article-title":"Chromogranins A and B and secretogranin II: evolutionary and functional aspects","volume":"192","author":"Montero-Hadjadje","year":"2008","journal-title":"Acta Physiol (Oxf)"},{"key":"2022031223042580500_B4","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1210\/er.2010-0027","article-title":"The extended granin family: structure, function, and biomedical implications","volume":"32","author":"Bartolomucci","year":"2011","journal-title":"Endocr Rev"},{"key":"2022031223042580500_B5","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1172\/JCI119686","article-title":"Novel autocrine feedback control of catecholamine release. 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