Leptin-Insulin Interrelationships

Thomas-Geevarghese, Asha; Ratner, Robert E.

doi:10.1007/978-0-387-31416-7_5

Cited by 2 publications

(3 citation statements)

References 55 publications

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“…However, this time to time aforesaid is not always predictable, and e.g. some researches point out that leptin can control insulin somehow (14) . This diagram is mathematical modeling biased.…”

Section: Food Intake Vs Metabolism: Bodyweight Control As a Soup Of E...mentioning

confidence: 99%

Some insights into an integrative mathematical model: a prototype-model for bodyweight and energy homeostasis

Pires¹

2016

G&S

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The ambition of this document is to set in evidence the prerequisite for integrative (mathematical) models, mechanism-based models, for appetite/bodyweight control. For achieving this goal, it is provided a scrutinized literature review and it is organized them in such a way to make the point. The quantitative methods exploited by the authors are called differential equations solved numerically; they are discussed briefly since it is not our goal herein to handle details. On the current state of the art, there is no mathematical model to the best of the author’s knowledge targeting at integrating several hormones at once in mathematical descriptions: even for single hormones, the literature is either occasional or do not exist at all; it is depicted some results for simple models already built. As it can be seen, the functions and roles seem fuzzy, most hormones seem to be piloting the same undertaking. The key challenge from a mathematical modeling perspective is how to separate properly the mechanisms of each hormone. The kind of pursuit presented herein could initiate an imperative cascade of mathematical modeling applied to metabolism of bodyweight control and energy homeostasis.

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Section: Food Intake Vs Metabolism: Bodyweight Control As a Soup Of E...mentioning

confidence: 99%

Some insights into an integrative mathematical model: a prototype-model for bodyweight and energy homeostasis

Pires¹

2016

G&S

View full text Add to dashboard Cite

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“…Recent studies supported a bidirectional feedback loop between adipose tissue and the beta-cells via leptin and insulin, (Kieffer and Habener 2000;Seufert 2004). The leptin-insulin interrelationship, nevertheless, is complex and remains controversial (Ceddia, Koistinen et al 2002;Thomas-Geevarghese and Ratner 2007). Briefly, insulin is an adipogenic hormone that enhances the storage of fat tissue and stimulates leptin secretion from adipocytes (Zheng, Jones et al 1996).…”

Section: The Role Of Leptin In Glucose Metabolism and Type 2 Diabetesmentioning

confidence: 99%

“…Indeed, diet induced weight loss is followed closely by a reduction in plasma leptin level and a coincidental increase in insulin sensitivity (Considine, Sinha et al 1996). However, the relationship between leptin and insulin is not straightforward (Ceddia, Koistinen et al 2002;Thomas-Geevarghese and Ratner 2007). A physiological concentration of leptin (1-10 nM) significantly suppressed insulin secretion, whereas high concentration (100 nM) was ineffective (Pallett, Morton et al 1997).…”

Section: The Role Of Leptin In Glucose Metabolism and Type 2 Diabetesmentioning

confidence: 99%

Structural and functional changes of pancreatic beta-cells during the progression of disease in the Leprdb model of type 2 diabetes

Hoang¹

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It is well established that changes in insulin secretion play an important role in the pathogenesis of type 2 diabetes. However, the underlying mechanisms of secretory changes occurring at the pancreatic beta-cell level are not fully elucidated. Therefore, this thesis focuses on the modulation of beta-cell function, particularly insulin granule exocytosis, during the progression of type 2 diabetes using the BKS.Cg-Dock7m+/+Lepr db /J (Lepr db mice) as a model of disease.I applied a variety of in vivo and in vitro methods to this project and further refined a livecell two-photon assay which I used to measure the numbers and kinetics of granule fusion events within intact islets.Using this latter technique, in the first part of the project I aimed to test a prevalent hypothesis that granule fusion behaviour changes in disease. Three indices of the post-fusion granule behaviour were compared between islets from animals with overt diabetes (db/db) and wild type. There was no difference in two indices of the fusion-granule behaviour; lifetime of granule fusion and post-fusion fluorescence intensity. The only change was a small increase in the percentage of recaptured granules (or "kiss-and-run" exocytosis) in db/db islets. In contrast to this minor change in granule fusion kinetics, further work showed that the main secretory deficit of frank diabetes, in db/db islets, is due to the loss of responding beta-cells and a reduction in the numbers of exocytic fusing granules in the remaining responsive cells.In the second part of the project I studied disease progression in the Lepr db model. Based on the area under the curve of the glucose tolerance tests, each db/db mouse was classified into one of four stages of disease, ranging from pre-diabetes (stage 1) to severe diabetes (stage 4). The results indicated that changes in islet size and insulin content occurred across all stages of disease severity.At stage 1, there was an increase in islet insulin content due to both an increased number of betacells and increased insulin content in each cell, whereas at stages 2-4, there was a progressive loss of islet insulin content that is a reflection of loss of content from individual beta-cells.Finally, in terms of beta-cell function, the data revealed that modulation of function characterised all stages of disease severity in db/db mice. In stage 1 there was an upregulation in the number of fusion of insulin-containing granules as well as the prevalence of compound exocytosis.At later disease stages there was a loss of glucose-induced insulin-granule fusion which my data indicated was due to impairment in glucose sensing. This work demonstrates that beta-cell function is intimately associated with pre-diabetes and progression to diabetes and adds weight to clinical strategies for therapeutic intervention as early as possible. Page | iiIn summary, the results show that the major factors in the disease phenotype are changes in the numbers of responding beta-cells and the numbers of fusing granules rather than the kinetic...

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Leptin-Insulin Interrelationships

Cited by 2 publications

References 55 publications

Some insights into an integrative mathematical model: a prototype-model for bodyweight and energy homeostasis

Some insights into an integrative mathematical model: a prototype-model for bodyweight and energy homeostasis

Structural and functional changes of pancreatic beta-cells during the progression of disease in the Leprdb model of type 2 diabetes

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