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Here we focus on the role of leptin, the product of the obesity (\n                    <jats:italic>ob<\/jats:italic>\n                    ) gene, in the development of insulin resistance and diabetes associated with obesity and lipoatrophy. We review the reported effects of leptin on whole body glucose metabolism and compare and contrast these with direct effects on skeletal muscle, fat and liver. This summary of paradoxical observations on the effects of leptin on glucose homeostasis and the ability of leptin to induce or improve insulin resistance suggests that a complex interplay exists between direct peripheral and centrally mediated effects of the hormone. Evidence suggesting that leptin acts as a mediator of insulin release from pancreatic \u03b2 cells is reviewed. Finally, intracellular signaling mechanisms stimulated by both leptin and insulin are discussed, with potential points of cross\u2010talk suggested.\u2014Ceddia, R. B., Koistinen, H. A., Zierath, J. R., Sweeney, G. Analysis of paradoxical observations on the association between leptin and insulin resistance.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 16, 1163\u20131176 (2002)\n                  <\/jats:p>","DOI":"10.1096\/fj.02-0158rev","type":"journal-article","created":{"date-parts":[[2002,9,30]],"date-time":"2002-09-30T13:43:21Z","timestamp":1033393401000},"page":"1163-1176","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":189,"title":["Analysis of paradoxical observations on the association between leptin and insulin resistance"],"prefix":"10.1096","volume":"16","author":[{"given":"Rolando B.","family":"Ceddia","sequence":"first","affiliation":[{"name":"Department of Biology York University  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heikki A.","family":"Koistinen","sequence":"additional","affiliation":[{"name":"Integrative Physiology, Karolinska Institute  Stockholm Sweden"},{"name":"Department of Medicine, Division of Cardiology Helsinki University Central Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juleen R.","family":"Zierath","sequence":"additional","affiliation":[{"name":"Integrative Physiology, Karolinska Institute  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Sweeney","sequence":"additional","affiliation":[{"name":"Department of Biology York University  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/372425a0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7624777"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7624778"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7624776"},{"key":"e_1_2_8_6_1","article-title":"Leptin, leptin receptors, and the control of body weight","volume":"56","author":"Friedman J. 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