{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:46:06Z","timestamp":1791207966201,"version":"4.1.0"},"reference-count":34,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:p>The role of peripheral vs. central circadian rhythms and Clock in the maintenance of metabolic homeostasis and with aging was examined by using Clock<jats:sup>\u039419<\/jats:sup>+MEL mice. These have preserved suprachiasmatic nucleus and pineal gland rhythmicity but arrhythmic Clock gene expression in the liver and skeletal muscle. Clock<jats:sup>\u039419<\/jats:sup>+MEL mice showed fasting hypoglycemia in young-adult males, fasting hyperglycemia in older females, and substantially impaired glucose tolerance overall. Clock<jats:sup>\u039419<\/jats:sup>+MEL mice had substantially reduced plasma insulin and plasma insulin\/glucose nocturnally in males and during a glucose tolerance test in females, suggesting impaired insulin secretion. Clock<jats:sup>\u039419<\/jats:sup>+MEL mice had reduced hepatic expression and loss of rhythmicity of gck, pfkfb3, and pepck mRNA, which is likely to impair glycolysis and gluconeogenesis. Clock<jats:sup>\u039419<\/jats:sup>+MEL mice also had reduced glut4 mRNA in skeletal muscle, and this may contribute to poor glucose tolerance. Whole body insulin tolerance was enhanced in Clock<jats:sup>\u039419<\/jats:sup>+MEL mice, however, suggesting enhanced insulin sensitivity. These responses occurred although the Clock<jats:sup>\u039419<\/jats:sup>mutation did not cause obesity and reduced plasma free fatty acids while increasing plasma adiponectin. These studies on clock-gene disruption in peripheral tissues and metabolic homeostasis provide compelling evidence of a relationship between circadian rhythms and the glucose\/insulin and adipoinsular axes. It is, however, premature to declare that clock-gene disruption causes the full metabolic syndrome.<\/jats:p>","DOI":"10.1152\/ajpregu.00018.2007","type":"journal-article","created":{"date-parts":[[2007,8,9]],"date-time":"2007-08-09T00:54:15Z","timestamp":1186620855000},"page":"R1528-R1537","source":"Crossref","is-referenced-by-count":116,"title":["Metabolic homeostasis in mice with disrupted<i>Clock<\/i>gene expression in peripheral tissues"],"prefix":"10.1152","volume":"293","author":[{"given":"David J.","family":"Kennaway","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Owens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athena","family":"Voultsios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael 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