PWD/PhJ mice have a genetically determined increase in nutrient-stimulated insulin secretion

PWD/PhJ mice have a genetically determined increase in nutrient-stimulated insulin secretion PWD/PhJ (PWD) is a wild-derived inbred mouse strain unrelated to commonly studied strains, such as C57BL/6J (B6). A chromosome substitution panel with PWD chromosomes transferred into the B6 background is commercially available and will facilitate genetic analysis of this strain. We have previously shown that the PWD strain is a model of primary fasting hyperinsulinemia. To identify more specific phenotypes affected by the genetic variation in PWD compared to B6 mice, we examined physiological mechanisms that may contribute to their elevated insulin levels. PWD mice had increased nutrient-stimulated insulin secretion due to factors inherent to their pancreatic islets. Insulin secretion responses to glucose, palmitate, and the metabolic intermediate α-ketoisocaproate were increased ~2-fold in islets from PWD mice compared to B6 islets. In contrast, there were no strain differences in processes affecting insulin secretion downstream of β cell depolarization. PWD mice tended to have larger but fewer islets than B6 mice, resulting in similar insulin-staining areas and insulin content per unit of pancreatic tissue. However, pancreata of PWD mice were smaller, resulting in reduced total β cell mass and pancreatic insulin content compared to B6 mice. Combined, these data suggest that the elevated fasting insulin levels in PWD mice result from increased generation of metabolic signals leading to β cell depolarization and insulin secretion. Identification of the genetic differences underlying the enhanced nutrient-stimulated insulin secretion in this model may lead to new approaches to appropriately modulate insulin secretion for the treatment of obesity and type 2 diabetes. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Mammalian Genome Springer Journals

PWD/PhJ mice have a genetically determined increase in nutrient-stimulated insulin secretion

Loading next page...
 
/lp/springer_journal/pwd-phj-mice-have-a-genetically-determined-increase-in-nutrient-EY0MDvmCcO
Publisher
Springer US
Copyright
Copyright © 2015 by Springer Science+Business Media New York
Subject
Life Sciences; Cell Biology; Anatomy; Zoology
ISSN
0938-8990
eISSN
1432-1777
D.O.I.
10.1007/s00335-015-9554-2
Publisher site
See Article on Publisher Site

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 12 million articles from more than
10,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Unlimited reading

Read as many articles as you need. Full articles with original layout, charts and figures. Read online, from anywhere.

Stay up to date

Keep up with your field with Personalized Recommendations and Follow Journals to get automatic updates.

Organize your research

It’s easy to organize your research with our built-in tools.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

Monthly Plan

  • Read unlimited articles
  • Personalized recommendations
  • No expiration
  • Print 20 pages per month
  • 20% off on PDF purchases
  • Organize your research
  • Get updates on your journals and topic searches

$49/month

Start Free Trial

14-day Free Trial

Best Deal — 39% off

Annual Plan

  • All the features of the Professional Plan, but for 39% off!
  • Billed annually
  • No expiration
  • For the normal price of 10 articles elsewhere, you get one full year of unlimited access to articles.

$588

$360/year

billed annually
Start Free Trial

14-day Free Trial