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

Khan, A ; Narangoda, S ; Ahrén, Bo LU ; Holm, Cecilia LU ; Sundler, Frank LU and Efendic, S (2001) In International Journal of Obesity 25(6). p.816-821
Abstract
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... (More)
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. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
insulin secretion, glucose-6-phosphatase, hormone-sensitive lipase, islets, leptin
in
International Journal of Obesity
volume
25
issue
6
pages
816 - 821
publisher
Nature Publishing Group
external identifiers
  • pmid:11439295
  • scopus:0034950377
  • pmid:11439295
ISSN
1476-5497
DOI
10.1038/sj.ijo.0801628
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medicine (Lund) (013230025), Molecular Endocrinology (013212018), Neuroendocrine Cell Biology (013212008)
id
cddcfa7c-1254-4e7b-803c-43fa4a40d5aa (old id 1120368)
date added to LUP
2016-04-01 12:04:42
date last changed
2024-10-08 20:51:54
@article{cddcfa7c-1254-4e7b-803c-43fa4a40d5aa,
  abstract     = {{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&lt;0.05) and 16.7 mM (by 85%; P&lt;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.}},
  author       = {{Khan, A and Narangoda, S and Ahrén, Bo and Holm, Cecilia and Sundler, Frank and Efendic, S}},
  issn         = {{1476-5497}},
  keywords     = {{insulin secretion; glucose-6-phosphatase; hormone-sensitive lipase; islets; leptin}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{816--821}},
  publisher    = {{Nature Publishing Group}},
  series       = {{International Journal of Obesity}},
  title        = {{Long-term leptin treatment of ob/ob mice improves glucose-induced insulin secretion}},
  url          = {{http://dx.doi.org/10.1038/sj.ijo.0801628}},
  doi          = {{10.1038/sj.ijo.0801628}},
  volume       = {{25}},
  year         = {{2001}},
}