{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:19:40Z","timestamp":1784557180092,"version":"3.55.0"},"reference-count":38,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:p>\n                    Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited syndrome characterized by multiple tumors in the parathyroid glands, endocrine pancreas and anterior pituitary. Recent clinical studies have revealed a strong association between MEN1 syndrome and the risk of developing diabetes mellitus; however, the underlying mechanisms remain unknown. In this study, heterozygous\n                    <jats:italic>Men1<\/jats:italic>\n                    knockout (\n                    <jats:italic>Men1<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    ) mice were used as MEN1 models to investigate MEN1-associated glucose metabolic phenotypes and mechanisms. Heterozygous deficiency of\n                    <jats:italic>Men1<\/jats:italic>\n                    in 12-month-old male mice induced fasting hyperglycemia, along with increased serum insulin levels. However, male\n                    <jats:italic>Men1<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice did not show insulin resistance, as evidenced by Akt activation in hepatic tissues and an insulin tolerance test. Increased glucose levels following pyruvate challenge and expression of key gluconeogenic genes suggested increased hepatic glucose output in the male\n                    <jats:italic>Men1<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice. This effect could be partly due to higher basal serum glucagon levels, which resulted from pancreatic islet cell proliferation induced by heterozygous loss of\n                    <jats:italic>Men1<\/jats:italic>\n                    . Taken together, our results indicate that fasted male\n                    <jats:italic>Men1<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice, in the early stage of development of MEN1, display glucose metabolic disorders. These disorders are caused not by direct induction of insulin resistance, but via increased glucagon secretion and the consequent stimulation of hepatic glucose production.\n                  <\/jats:p>","DOI":"10.1530\/joe-16-0090","type":"journal-article","created":{"date-parts":[[2016,7,18]],"date-time":"2016-07-18T22:49:25Z","timestamp":1468882165000},"page":"347-355","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":1,"title":["Male Men1 heterozygous mice exhibit fasting hyperglycemia in the early stage of MEN1"],"prefix":"10.1530","volume":"230","author":[{"given":"Zhongxiuzi","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Basic Medical SciencesMedical College, Xiamen University, Xiamen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Basic Medical SciencesMedical College, Xiamen University, 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