Transgenic reexpression of GLUT1 or GLUT2 in pancreatic beta cells rescues GLUT2-null mice from early death and restores normal glucose-stimulated insulin secretion.

GLUT2-null mice are hyperglycemic, hypoinsulinemic, hyperglucagonemic, and glycosuric and die within the first 3 weeks of life. Their endocrine pancreas shows a loss of first phase glucose-stimulated insulin secretion (GSIS) and inverse alpha to beta cell ratio. Here we show that reexpression by transgenesis of either GLUT1 or GLUT2 in the pancreatic beta cells of these mice allowed mouse survival and breeding. The rescued mice had normal-fed glycemia but fasted hypoglycemia, glycosuria, and an elevated glucagon to insulin ratio. Glucose tolerance was, however, normal. In vivo, insulin secretion assessed following hyperglycemic clamps was normal. In vitro, islet perifusion studies revealed that first phase of insulin secretion was restored as well by GLUT1 or GLUT2, and this was accompanied by normalization of the glucose utilization rate. The ratio of pancreatic insulin to glucagon and volume densities of alpha to beta cells were, however, not corrected. These data demonstrate that 1) reexpression of GLUT1 or GLUT2 in beta cells is sufficient to rescue GLUT2-null mice from lethality, 2) GLUT1 as well as GLUT2 can restore normal GSIS, 3) restoration of GSIS does not correct the abnormal composition of the endocrine pancreas. Thus, normal GSIS does not depend on transporter affinity but on the rate of uptake at stimulatory glucose concentrations.

Systems Genetics of Metabolism: The Use of the BXD Murine Reference Panel for Multiscalar Integration of Traits.

Metabolic homeostasis is achieved by complex molecular and cellular networks that differ significantly among individuals and are difficult to model with genetically engineered lines of mice optimized to study single gene function. Here, we systematically acquired metabolic phenotypes by using the EUMODIC EMPReSS protocols across a large panel of isogenic but diverse strains of mice (BXD type) to study the genetic control of metabolism. We generated and analyzed 140 classical phenotypes and deposited these in an open-access web service for systems genetics (www.genenetwork.org). Heritability, influence of sex, and genetic modifiers of traits were examined singly and jointly by using quantitative-trait locus (QTL) and expression QTL-mapping methods. Traits and networks were linked to loci encompassing both known variants and novel candidate genes, including alkaline phosphatase (ALPL), here linked to hypophosphatasia. The assembled and curated phenotypes provide key resources and exemplars that can be used to dissect complex metabolic traits and disorders.

Quantitative genetics of learning ability and resistance to stress in Drosophila melanogaster.

Even though laboratory evolution experiments have demonstrated genetic variation for learning ability, we know little about the underlying genetic architecture and genetic relationships with other ecologically relevant traits. With a full diallel cross among twelve inbred lines of Drosophila melanogaster originating from a natural population (0.75 < F < 0.93), we investigated the genetic architecture of olfactory learning ability and compared it to that for another behavioral trait (unconditional preference for odors), as well as three traits quantifying the ability to deal with environmental challenges: egg-to-adult survival and developmental rate on a low-quality food, and resistance to a bacterial pathogen. Substantial additive genetic variation was detected for each trait, highlighting their potential to evolve. Genetic effects contributed more than nongenetic parental effects to variation in traits measured at the adult stage: learning, odorant perception, and resistance to infection. In contrast, the two traits quantifying larval tolerance to low-quality food were more strongly affected by parental effects. We found no evidence for genetic correlations between traits, suggesting that these traits could evolve at least to some degree independently of one another. Finally, inbreeding adversely affected all traits.

Uncovering the genetic basis of adaptive change: on the intersection of landscape genomics and theoretical population genetics

A workshop recently held at the Ecole Polytechnique Federale de Lausanne (EPFL, Switzerland) was dedicated to understanding the genetic basis of adaptive change, taking stock of the different approaches developed in theoretical population genetics and landscape genomics and bringing together knowledge accumulated in both research fields. Indeed, an important challenge in theoretical population genetics is to incorporate effects of demographic history and population structure. But important design problems (e.g. focus on populations as units, focus on hard selective sweeps, no hypothesis-based framework in the design of the statistical tests) reduce their capability of detecting adaptive genetic variation. In parallel, landscape genomics offers a solution to several of these problems and provides a number of advantages (e.g. fast computation, landscape heterogeneity integration). But the approach makes several implicit assumptions that should be carefully considered (e.g. selection has had enough time to create a functional relationship between the allele distribution and the environmental variable, or this functional relationship is assumed to be constant). To address the respective strengths and weaknesses mentioned above, the workshop brought together a panel of experts from both disciplines to present their work and discuss the relevance of combining these approaches, possibly resulting in a joint software solution in the future.

Lake Restoration 2007 Report and 2008 Plan, December 28, 2007

The Department of Natural Resources (IDNR) Lake Restoration Program focuses on restoring impaired lakes to improve the quality of life for Iowans. Communities are rallying around their water resources as they seek population growth and economic success. Communities of the Iowa Great Lakes Region, Storm Lake, Crystal Lake, Creston and Clear Lake are obvious examples, but other communities including Lake View and Brighton are identifying the importance of lakes for their futures as well. The distribution and nature of Vision Iowa grants, Community Attraction and Tourism grants, and now, Great Places, all further emphasize the importance of water to community, quality of life and economic growth.

Lake Restoration 2008 Report and 2009 Plan, December 30, 2008

The Department of Natural Resources (IDNR) Lake Restoration Program focuses on restoring impaired lakes to improve the quality of life for Iowans. Communities are rallying around their water resources as they seek population growth and economic success. Communities of the Iowa Great Lakes Region, Storm Lake, Crystal Lake, Creston and Clear Lake are obvious examples, but other communities including Lake View and Brighton are identifying the importance of lakes for their futures as well. The distribution and nature of Vision Iowa grants, Community Attraction and Tourism grants, and now, Great Places, all further emphasize the importance of water to community, quality of life and economic growth.

Lake Restoration 2009 Report and 2010 Plan, December 30, 2009

The Department of Natural Resources (IDNR) Lake Restoration Program focuses on restoring impaired lakes to improve the quality of life for Iowans. Communities are rallying around their water resources as they seek population growth and economic success. Communities of the Iowa Great Lakes Region, Storm Lake, Crystal Lake, Creston and Clear Lake are obvious examples, but other communities including Lake View and Brighton are identifying the importance of lakes for their futures as well. The distribution and nature of Vision Iowa grants, Community Attraction and Tourism grants, and now, Great Places, all further emphasize the importance of water to community, quality of life and economic growth.

Lake Restoration 2010 Report and 2011 Plan, December 30, 2010

The Department of Natural Resources (IDNR) Lake Restoration Program focuses on restoring impaired lakes to improve the quality of life for Iowans. Communities are rallying around their water resources as they seek population growth and economic success. Communities of the Iowa Great Lakes Region, Storm Lake, Crystal Lake, Creston and Clear Lake are obvious examples, but other communities including Lake View and Brighton are identifying the importance of lakes for their futures as well. The distribution and nature of Vision Iowa grants, Community Attraction and Tourism grants, and now, Great Places, all further emphasize the importance of water to community, quality of life and economic growth.

Lake Restoration 2011 Report and 2012 Plan, December 30, 2011

The Department of Natural Resources (IDNR) Lake Restoration Program focuses on restoring impaired lakes to improve the quality of life for Iowans. Communities are rallying around their water resources as they seek population growth and economic success. Communities of the Iowa Great Lakes Region, Storm Lake, Crystal Lake, Creston and Clear Lake are obvious examples, but other communities including Lake View and Brighton are identifying the importance of lakes for their futures as well. The distribution and nature of Vision Iowa grants, Community Attraction and Tourism grants, and now, Great Places, all further emphasize the importance of water to community, quality of life and economic growth.

Lake Restoration 2012 Report and 2013 Plan, December 31, 2012

The Department of Natural Resources (IDNR) Lake Restoration Program focuses on restoring impaired lakes to improve the quality of life for Iowans. Communities are rallying around their water resources as they seek population growth and economic success. Communities of the Iowa Great Lakes Region, Storm Lake, Crystal Lake, Creston and Clear Lake are obvious examples, but other communities including Lake View and Brighton are identifying the importance of lakes for their futures as well. The distribution and nature of Vision Iowa grants, Community Attraction and Tourism grants, and now, Great Places, all further emphasize the importance of water to community, quality of life and economic growth.

Lake Restoration 2013 Report and 2014 Plan, December 31, 2013

The Department of Natural Resources (IDNR) Lake Restoration Program focuses on restoring impaired lakes to improve the quality of life for Iowans. Communities are rallying around their water resources as they seek population growth and economic success. Communities of the Iowa Great Lakes Region, Storm Lake, Crystal Lake, Creston and Clear Lake are obvious examples, but other communities including Lake View and Brighton are identifying the importance of lakes for their futures as well. The distribution and nature of Vision Iowa grants, Community Attraction and Tourism grants, and now, Great Places, all further emphasize the importance of water to community, quality of life and economic growth.

Lake Restoration 2014 Report and 2015 Plan, December 31, 2014

The Department of Natural Resources (IDNR) Lake Restoration Program focuses on restoring impaired lakes to improve the quality of life for Iowans. Communities are rallying around their water resources as they seek population growth and economic success. Communities of the Iowa Great Lakes Region, Storm Lake, Crystal Lake, Creston and Clear Lake are obvious examples, but other communities including Lake View and Brighton are identifying the importance of lakes for their futures as well. The distribution and nature of Vision Iowa grants, Community Attraction and Tourism grants, and now, Great Places, all further emphasize the importance of water to community, quality of life and economic growth.