Hyper-variability in Circulating Insulin Levels and Physiological Outcomes to High Fat Feeding in Male Ins1-/-:Ins2+/- Mice in a Specific Pathogen-free Facility


This paper from Jim Johnson’s group (@JimJohnsonSci) was posted to bioRxiv at http://dx.doi.org/10.1101/031799.

Abstract: Insulin is an essential hormone with key roles in energy homeostasis and body composition. Mice and rats, unlike other mammals, have two insulin genes: the rodent-specific Ins1 gene and the ancestral Ins2 gene. The relationships between insulin gene dosage and obesity has previously been explored in male and female Ins2-/- mice with full or reduced Ins1 dosage, as well as in female Ins1-/- mice with full or partial Ins2 dosage. We report herein unexpected hyper-variability in circulating insulin and physiological responses to high fat feeding in male Ins1-/-:Ins2+/- mice. Two large cohorts of Ins1-/-:Ins2+/- mice and their Ins1-/-:Ins2+/+ littermates were fed chow diet or high fat diet (HFD) from weaning and housed in specific pathogen-free (SPF) conditions. Cohort A and cohort B were studied one year apart. Contrary to female mice from the same litters, inactivating one Ins2 allele on the complete Ins1-null background did not cause a consistent reduction of circulating insulin in male mice. In cohort A, HFD-fed males showed an equivalent degree of insulin hypersecretion and weight gain, regardless of Ins2 dosage. In cohort B, Ins1-/-:Ins2+/- males showed decreased insulin levels and body mass, compared to Ins1-/-:Ins2+/+ littermates. While experimental conditions were held consistent between cohorts, we found that HFD-fed Ins1-/-:Ins2+/- mice with lower insulin levels had increased corticosterone. Collectively, these observations highlight the hyper-variability and range of phenotypic characteristics modulated by Ins2 gene dosage, specifically in male mice.



Preprints are papers that are shared, discussed or available prior to peer review publication.  This may sound new, or odd but in reality this happens in closed doors all the time.  People write papers, share them with trusted colleagues and then submit them to journals for peer review.  This would work fine, but for many reasons, papers often take a very long time to get published.  This means that we can’t build on, or apply that work unless we are one of the trusted colleagues, or until it is published.  This concept has been described in detail in Science, in a PLOS One article, and many other places.

The Solution?

Other fields, physics and math especially, work differently.  They post paper before, or simultaneous to peer review on preprint servers (mainly arXiv), for discussion and review by a wider audience than just the small number of peer reviewers chosen by the journal.  Biology has been historically resistant to this idea, but recent services such as bioRxiv and Peer J Preprints have provided a platform for posting preprints.

The Problem with the Solution…

My sense is, right now there is insufficient engagement, commenting and advertisement of preprints, especially in the areas that I am interested in.  My group has started posting our manuscripts to bioRxiv (I discussed that rationale here) for comments, and has received much more detailed comments and suggestions in detailed peer-review than anything that came from these preprints.  I suspect that my experience is not atypical.  Even if preprints are being read, and considered, I think that right now there is not sufficient public discussion on these preprints, and if they are going to be useful, they need to be discussed.

What I Hope to Accomplish

I plan to use this blog as a forum to read and make some comments on pre-prints that I come accross that  are in my area.  My goal is to advertise them better, provide some (hopefully) useful feedback to the authors and to force myself to consider this route of discourse.  Basically, I am stealing this idea from Haldane’s Sieve, a blog that discusses preprints in the area of population and evolutionary genetics.  Also, if you would like to contribute, and have something to say about a pre-print, let me know.

Desjardins-Proulx, P., White, E., Adamson, J., Ram, K., Poisot, T., & Gravel, D. (2013). The Case for Open Preprints in Biology PLoS Biology, 11 (5) DOI: 10.1371/journal.pbio.1001563