JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Altered pancreatic growth and insulin secretion in WSB/EiJ mice.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
These data suggest that insulin secretion in WSB mice is blunted specifically in vivo, either due to a reduced insulin requirement and/or due to factors that are absent or destroyed in vitro. These studies also highlight the role of post-natal growth in determining adult ?-cell mass. Mice are important animal models for the study of metabolic physiology and the genetics of complex traits. Wild-derived inbred mouse strains, such as WSB/EiJ (WSB), are unrelated to the commonly studied mouse strains and are valuable tools to identify novel genes that modify disease risk. We have previously shown that in contrast to C57BL/6J (B6) mice, WSB mice fed a high fat diet do not develop hyperinsulinemia or insulin resistance, and had nearly undetectable insulin secretion in response to an intraperitoneal glucose challenge. As hyperinsulinemia may drive obesity and insulin resistance, we examined whether defects in ?-cell mass or function could contribute to the low insulin levels in WSB mice. In young WSB mice, ?-cell mass was similar to B6 mice. However, we found that adult WSB mice had reduced ?-cell mass due to reduced pancreatic weights. Pancreatic sizes were similar between the strains when normalized to body weight, suggesting their pancreatic size is appropriate to their body size in adults, but overall post-natal pancreatic growth was reduced in WSB mice compared to B6 mice. Islet architecture was normal in WSB mice. WSB mice had markedly increased insulin secretion from isolated islets in vitro. These data suggest that insulin secretion in WSB mice is blunted specifically in vivo, either due to a reduced insulin requirement and/or due to factors that are absent or destroyed in vitro. These studies suggest that WSB mice may provide novel insight into mechanisms regulating insulin secretion and also highlight the role of post-natal growth in determining adult ?-cell mass.
Related JoVE Video
Diabetes genes identified by genome-wide association studies are regulated in mice by nutritional factors in metabolically relevant tissues and by glucose concentrations in islets.
BMC Genet.
PUBLISHED: 02-21-2013
Show Abstract
Hide Abstract
Genome-wide association studies (GWAS) have recently identified many new genetic variants associated with the development of type 2 diabetes. Many of these variants are in introns of known genes or between known genes, suggesting they affect the expression of these genes. The regulation of gene expression is often tissue and context dependent, for example occurring in response to dietary changes, hormone levels, or many other factors. Thus, to understand how these new genetic variants associated with diabetes risk may act, it is necessary to understand the regulation of their cognate genes.
Related JoVE Video
Moo1 obesity quantitative trait locus in BTBR T+ Itpr3tf/J mice increases food intake.
Physiol. Genomics
PUBLISHED: 01-22-2013
Show Abstract
Hide Abstract
The rising prevalence of obesity is one of the greatest health challenges facing the world today. Discovery of genetic factors affecting obesity risk will provide important insight to its etiology that could suggest new therapeutic approaches. We have previously identified the Modifier of obese 1 (Moo1) quantitative trait locus (QTL) in a cross between leptin-deficient BTBR T(+) Itpr3(tf)/J (BTBR) and C57BL/6J (B6) mice. Understanding the mechanism by which this locus acts will aid in the identification of candidate genes. Here we refined the location of this QTL and sought to determine the mechanism by which Moo1 affects body weight. We found that the effects of Moo1 also alter high fat diet-induced obesity in mice having functional leptin. In detailed metabolic analyses we determined that this locus acts by increasing food intake in BTBR mice, without affecting energy expenditure. The expression levels of the main molecular mediators of food intake in the hypothalamus were not altered, suggesting this locus affects an independent pathway, consistent with its identification in mice lacking functional leptin. Finally, we show that the increased adiposity resulting from Moo1 is sufficient to affect glucose tolerance. These studies show that the Moo1 obesity QTL affects food intake, likely through a novel mechanism, and indicate that modulation of the underlying pathway may not only ameliorate obesity but also its clinical consequences.
Related JoVE Video
Insulin induces long-term depression of ventral tegmental area dopamine neurons via endocannabinoids.
Nat. Neurosci.
PUBLISHED: 01-02-2013
Show Abstract
Hide Abstract
The prevalence of obesity has markedly increased over the past few decades. Exploration of how hunger and satiety signals influence the reward system can help us understand non-homeostatic feeding. Insulin may act in the ventral tegmental area (VTA), a critical site for reward-seeking behavior, to suppress feeding. However, the neural mechanisms underlying insulin effects in the VTA remain unknown. We demonstrate that insulin, a circulating catabolic peptide that inhibits feeding, can induce long-term depression (LTD) of mouse excitatory synapses onto VTA dopamine neurons. This effect requires endocannabinoid-mediated presynaptic inhibition of glutamate release. Furthermore, after a sweetened high-fat meal, which elevates endogenous insulin, insulin-induced LTD is occluded. Finally, insulin in the VTA reduces food anticipatory behavior in mice and conditioned place preference for food in rats. Taken together, these results suggest that insulin in the VTA suppresses excitatory synaptic transmission and reduces anticipatory activity and preference for food-related cues.
Related JoVE Video
PWD/PhJ and WSB/EiJ mice are resistant to diet-induced obesity but have abnormal insulin secretion.
Endocrinology
PUBLISHED: 06-14-2011
Show Abstract
Hide Abstract
Recently, novel inbred mouse strains that are genetically distinct from the commonly used models have been developed from wild-caught mice. These wild-derived inbred strains have been included in many of the large-scale genomic projects, but their potential as models of altered obesity and diabetes susceptibility has not been assessed. We examined obesity and diabetes-related traits in response to high-fat feeding in two of these strains, PWD/PhJ (PWD) and WSB/EiJ (WSB), in comparison with C57BL/6J (B6). Young PWD mice displayed high fasting insulin levels, although they had normal insulin sensitivity. PWD mice subsequently developed a much milder and delayed-onset obesity compared with B6 mice but became as insulin resistant. PWD mice had a robust first-phase and increased second-phase glucose-stimulated insulin secretion in vivo, rendering them more glucose tolerant. WSB mice were remarkably resistant to diet-induced obesity and maintained very low fasting insulin throughout the study. WSB mice exhibited more rapid glucose clearance in response to an insulin challenge compared with B6 mice, consistent with their low percent body fat. Interestingly, in the absence of a measurable in vivo insulin secretion, glucose tolerance of WSB mice was better than B6 mice, likely due to their enhanced insulin sensitivity. Thus PWD and WSB are two obesity-resistant strains with unique insulin secretion phenotypes. PWD mice are an interesting model that dissociates hyperinsulinemia from obesity and insulin resistance, whereas WSB mice are a model of extraordinary resistance to a high-fat diet.
Related JoVE Video
GIP-overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis.
PLoS ONE
Show Abstract
Hide Abstract
Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone that potentiates glucose-stimulated insulin secretion during a meal. Since GIP has also been shown to exert ?-cell prosurvival and adipocyte lipogenic effects in rodents, both GIP receptor agonists and antagonists have been considered as potential therapeutics in type 2 diabetes (T2DM). In the present study, we tested the hypothesis that chronically elevating GIP levels in a transgenic (Tg) mouse model would increase adipose tissue expansion and exert beneficial effects on glucose homeostasis. In contrast, although GIP Tg mice demonstrated enhanced ?-cell function, resulting in improved glucose tolerance and insulin sensitivity, they exhibited reduced diet-induced obesity. Adipose tissue macrophage infiltration and hepatic steatosis were both greatly reduced, and a number of genes involved in lipid metabolism/inflammatory signaling pathways were found to be down-regulated. Reduced adiposity in GIP Tg mice was associated with decreased energy intake, involving overexpression of hypothalamic GIP. Together, these studies suggest that, in the context of over-nutrition, transgenic GIP overexpression has the potential to improve hepatic and adipocyte function as well as glucose homeostasis.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.