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

Khan, Abdul Waheed; Narangoda, S; Åhrén, Bo; Holm, Cecilia; Sundler, F.; Efendić, Suad

doi:10.1038/sj.ijo.0801628

Cited by 26 publications

(20 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whereas sham-treated mice displayed a continuous adaptive growth of islet transplants, this growth was abolished and partially reversed under leptin treatment (Fig. 4 A and B), in agreement with earlier reports (20,21). At the end of the treatment, the proliferation of beta cells was virtually abolished in both the engrafted islets and the in situ pancreatic islets from leptin-treated ob/ob mice (Fig.…”

Section: Leptin Treatment Reduces Body Weight and Corrects Blood Glucosesupporting

confidence: 91%

“…4A). This is in accordance with the increased immunostaining for insulin perceived in islets from leptin-treated ob/ob mice (20). The normalization of insulin release in vivo after leptin treatment in the ob/ob mouse has been linked to mechanisms both dependent on and independent of food intake (21).…”

Section: Leptin Treatment Reduces Body Weight and Corrects Blood Glucosesupporting

confidence: 79%

See 1 more Smart Citation

Reporter islets in the eye reveal the plasticity of the endocrine pancreas

Ilegems

Dicker

Speier

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Significance An adaptive plasticity of the insulin-secreting pancreatic beta cells, located in the islets of Langerhans, is essential for maintaining proper blood glucose homeostasis under various functional demands. Understanding the molecular mechanisms underlying the regulation of beta cell mass and function is critically dependent on an in vivo monitoring system that can continuously report on the functional status of the islets. Because direct inspection of these islets is obstructed due to the fact that they are deeply embedded and scattered within the pancreas, we propose the use of “reporter islets” transplanted into the anterior chamber of the eye, serving as optically accessible indicators of islet plasticity in the pancreas and as a tool to individually assess effectiveness of specific treatment regimens.

show abstract

Section: Leptin Treatment Reduces Body Weight and Corrects Blood Glucosesupporting

confidence: 91%

Section: Leptin Treatment Reduces Body Weight and Corrects Blood Glucosesupporting

confidence: 79%

Reporter islets in the eye reveal the plasticity of the endocrine pancreas

Ilegems

Dicker

Speier

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…It is possible that the intracellular content of triglycerides will determine the effect, 35 and that leptin reduces the triglyceride burden, which at least in a rat model was followed by increased insulin secretion. 36 Consequently, it has been suggested that leptin regulates the metabolism of fatty acids in nonadipose tissue, 37 but owing to dysfunction in leptin signalling, i.e. leptin resistance, this function may not work properly in obesity and reduced b-cells function follows.…”

Section: Discussionmentioning

confidence: 99%

Leptin predicts the development of diabetes in Mauritian men, but not women: a population–based study

et al. 2007

View full text Add to dashboard Cite

Objective: To determine if levels of the adipocyte-derived hormone, leptin, predict the development of type 2 diabetes. Methods: Population-based surveys were undertaken in the multiethnic nation of Mauritius in 1987Mauritius in , 1992Mauritius in and 1998. Questionnaires, anthropometric measurements, and a 2-h 75-g oral glucose tolerance test were included. A cohort of 2330 participants who were free of diabetes, aged 25-79 years in 1987, and who were followed-up in 1992 and 1998 was studied. Serum leptin was measured in baseline samples. Glucose tolerance was classified according to WHO (World Health Organization) 1999 criteria. Results: In total, 456 subjects developed diabetes over 11 years with similar incidences in all ethnic groups (P ¼ 0.2). Baseline leptin correlated positively with anthropometric measurements, fasting and postload insulin and homeostasis model assessment indices (all Po0.001), and inversely with subsequent weight increase. Participants with incident diabetes had higher serum levels of leptin at baseline than those remaining nondiabetic (Po0.001). After adjustment for confounders, high leptin levels and high leptin/body mass index ratio were independently associated with incident diabetes over 11 years in men (odds ratio for top versus bottom quartile of leptin 2.18; 95% CI: 1.09-4.35), but not in women. Conclusion: We conclude that high leptin levels are associated with the future development of diabetes, and the association is independent of other factors in men, but not in women.

show abstract

“…Leptin has been demonstrated to inhibit insulin secretion in vitro (15,25,26). However, in vivo studies in diabetic models have shown that leptin treatment improves insulin secretion in ob/ob mice (27), and overexpression of the leptin receptor in a model homozygous for a mutation of the ObRb, the Zucker diabetic rat, restores GLUT2 expression and insulin secretion (28). By using an ObRb-specific antibody, we observed immunoreactivity for this receptor in the ␤-cells of both normal and high-fat islets with no apparent difference.…”

Section: Discussionmentioning

confidence: 99%

Altered β-Cell Distribution of pdx-1 and GLUT-2 After a Short-Term Challenge With a High-Fat Diet in C57BL/6J Mice

Reimer

Åhrén

2002

Diabetes

View full text Add to dashboard Cite

Mechanisms involved in the islet adaptation to insulin resistance were examined in mice of the C57BL/6J strain challenged with a high-fat (58%) diet for 8 weeks. Basal hyperglycemia commenced after 1 week, whereas hyperinsulinemia evolved after 8 weeks. Glucose elimination after an intravenous glucose challenge (1 g/kg) was significantly delayed after 1, 4, and 8 weeks on the high-fat diet compared with normal-diet-fed mice. This result was associated with unchanged insulin responses. However, glucose-stimulated insulin secretion from isolated islets was increased in a compensatory fashion at all glucose levels over a wide range (3.3-22 mmol/l) after 8 weeks on the high-fat diet, whereas no compensatory hypersecretion of insulin was evident after 1 or 4 weeks, except at 22 mmol/l glucose. Immunohistochemistry revealed that the islet architecture of insulin and glucagon cells remained intact in islets from mice fed a high-fat diet. However, the nuclear translocation of the homeobox transcription factor, pdx-1, and the plasma membrane translocation of GLUT2 were both impaired in high-fat-fed animals after 1 week. In contrast, the expression of the full-length leptin receptor (ObRb) was not affected by high-fat feeding. The study thus shows that 8 weeks are required for the development of a compensatory hypersecretion of insulin after high-fat feeding in mice, and even then the in vivo insulin secretion is insufficient to normalize impaired glucose tolerance. The early-onset islet dysfunction is accompanied by impaired ␤-cell trafficking of two factors, pdx-1 and GLUT-2, which are involved in ␤-cell proliferation and glucose recognition. The mechanisms compromising this ␤-cell trafficking remain to be established. Diabetes 51 (Suppl. 1):S138 -S143, 2002 I nsulin resistance is associated with islet adaptation ensuring adequate hyperinsulinemia to maintain normoglycemia. However, if the islet adaptation is impaired, hyperinsulinemia is inadequate and metabolic perturbations such as hyperglycemia might ensue (1). A model to study the mechanisms of impaired islet adaptation in insulin resistance is the high-fat feeding of C57BL/6J mice, which are especially susceptible to highfat treatment with regard to the development of glucose intolerance compared with other strains (2,3). We have previously shown that this model is associated with obesity, hyperglycemia, hyperinsulinemia, and hyperlipidemia (4); increased insulin mRNA expression in islets (5); and exaggerated insulin response to challenges with ␤-cell secretagogues (6,7). In contrast, the early islet changes after feeding these mice a high-fat diet are less well studied. Therefore, we have explored whether the development of glucose intolerance provoked by short-term feeding of a high-fat diet in C57BL/6J mice is associated with changes in insulin secretion, islet architecture of insulin and glucagon cells, and islet localization of factors thought to be of particular relevance for ␤-cell adaptation to insulin resistance. One such factor is the homeobox transcript...

show abstract

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

Cited by 26 publications

References 47 publications

Reporter islets in the eye reveal the plasticity of the endocrine pancreas

Reporter islets in the eye reveal the plasticity of the endocrine pancreas

Leptin predicts the development of diabetes in Mauritian men, but not women: a population–based study

Altered β-Cell Distribution of pdx-1 and GLUT-2 After a Short-Term Challenge With a High-Fat Diet in C57BL/6J Mice

Contact Info

Product

Resources

About