Leptin as an adjunct of insulin therapy in insulin-deficient diabetes

F. Miyanaga, Y. Ogawa, K. Ebihara, S. Hidaka, T. Tanaka, S. Hayashi, H. Masuzaki, K. Nakao

研究成果: Contribution to journalArticle査読

42 被引用数 (Scopus)

抄録

Aims/hypothesis. The purpose of this study was to assess the therapeutic implication of leptin in insulin-deficient diabetes. Methods. Insulin-deficient diabetes was induced by streptozotocin (STZ) in transgenic skinny mice overexpressing leptin. Plasma concentrations of glucose, insulin, and leptin were measured. The effects on body weight, food intake, and hypothalamic gene expressions were analyzed. After diabetes was induced, graded doses of insulin ranging from 0.4 to 51.2 mU·g-1·day-1 were injected. Co-administration of leptin and insulin was also carried out using osmotic pumps. Results. After STZ injection, both transgenic and nontransgenic littermates developed marked hyperglycaemia as a result of severe hypoinsulinaemia [termed diabetic transgenic skinny mice overexpressing leptin (diabetic TGM) and diabetic non-transgenic littermates (diabetic WT) respectively], although diabetic TGM were more sensitive to exogenously administered insulin than diabetic WT. Diabetic WT were hypoleptinaemic and hyperphagic relative to non-diabetic WT, whereas diabetic TGM, which remained hyperleptinaemic, were less hyperphagic than diabetic WT. After STZ injection, hypothalamic expressions of orexigenic and anorexigenic peptide mRNAs were upregulated and down-regulated, respectively, in diabetic WT, whereas they were unchanged in diabetic TGM. Diabetic TGM became normoglycaemic, when treated with insulin at such doses that did not improve hyperglycaemia in diabetic WT. We found that a subthreshold dose of insulin that does not affect glucose homeostasis is effective in improving the diabetes in normal mice rendered diabetic by STZ injection, when combined with leptin. Conclusions/ interpretation. This study suggests that leptin could be used as an adjunct of insulin therapy in insulin-deficient diabetes, thereby providing an insight into the therapeutic implication of leptin as an anti-diabetic agent.

本文言語英語
ページ(範囲)1329-1337
ページ数9
ジャーナルDiabetologia
46
10
DOI
出版ステータス出版済み - 10 2003
外部発表はい

All Science Journal Classification (ASJC) codes

  • 内科学
  • 内分泌学、糖尿病および代謝内科学

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