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Cecilia Holm

Professor

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Long-term leptin treatment of ob/ob mice improves glucose-induced insulin secretion

Author

  • A Khan
  • S Narangoda
  • Bo Ahrén
  • Cecilia Holm
  • Frank Sundler
  • S Efendic

Summary, in English

OBJECTIVE: Previous studies have demonstrated that leptin inhibits glucose-stimulated insulin secretion from isolated islets, although a lack of leptin effect on insulin secretion has also been reported. The effect of long term in vivo leptin treatment of insulin secretion has, however, not been established. Therefore, in the present study, we have evaluated the effect of long term in vivo treatment of leptin on glucose-induced insulin secretion in ob/ob mice. METHODS: After 7 days' treatment of leptin (100 microg daily s.c.), insulin release was measured in isolated islets by batch incubation followed by radioimmunoassay. Glucose utilization and oxidation were measured by measuring the formation of (3)H(2)O and (14)CO(2) from [5-(3)H] and [U-(14)C] glucose, respectively. Glucose-6-phosphatase activity was measured by measuring the conversion of (14)C-glucose-6-P to (14)C-glucose. In addition, immunohistochemistry of pancreatic specimens was undertaken for study of expression of insulin, GLUT-2 and hormone-sensitive lipase (HSL). RESULTS: Leptin treatment significantly improved insulin secretion both at 5.5 mM (by 15%; P<0.05) and 16.7 mM (by 85%; P<0.001) glucose, compared to vehicle-treated controls. Furthermore, whereas leptin treatment did not affect islet insulin or DNA contents, a significant decrease in islet triglyceride content and glucose-6-phosphatase activity was observed. Moreover, the immunocytochemical data revealed an increased immunostaining for insulin, GLUT-2 and hormone-sensitive lipase (HSL) in islets from leptin-treated ob/ob mice. CONCLUSION: The results suggest that long-term leptin treatment of ob/ob mice improves glucose-stimulated insulin secretion in parallel with reduced glucose-6-phosphatase activity, increased HSL and decreased triglyceride levels in islets. These perturbations may explain the improvement of glucose-stimulated insulin secretion induced by leptin.

Department/s

  • Medicine, Lund
  • Molecular Endocrinology
  • Department of Experimental Medical Science

Publishing year

2001

Language

English

Pages

816-821

Publication/Series

International Journal of Obesity

Volume

25

Issue

6

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Nutrition and Dietetics

Keywords

  • insulin secretion
  • glucose-6-phosphatase
  • hormone-sensitive lipase
  • islets
  • leptin

Status

Published

Research group

  • Molecular Endocrinology

ISBN/ISSN/Other

  • ISSN: 1476-5497