Allelic variation on chromosome 5 controls β-cell mass expansion during hyperglycemia in leptin receptor-deficient diabetes mice

Na Luo, Mei Liu Shun, Hong Liu, Qiong Li, Qun Xu, Xi Sun, Brandi Davis, Jing Li, Streamson C. Chua, Jr.

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Leptin signaling is a critical component of normal insulin sensitivity. Overt hyperglycemia and type 2 diabetes mellitus can be manifested in states of leptin signaling deficiencies by the additional effects of other genetic factors. We have previously described the contrasting insulin sensitivities and glycemic states of two congenic diabetes (db/db) mouse strains. C57BL/6J db/db mice have mild insulin resistance and achieve euglycemia with mild hyperinsulinemia. FVB db/db mice have severe insulin resistance and are hyperglycemic despite escalating hyperinsulinemia with expanded pancreatic β-cell mass. Analysis of obese progeny from the two reciprocal back-crosses suggests that genetic modifiers for insulin sensitivity are separable from loci that modulate β-cell mass. A genome scan of the backcross to FVB suggests that one or more modifier genes are present on chromosome 5. This evidence is supported by the phenotypes of multiple incipient congenic strains wherein the hyperglycemia observed in obese FVB mice is reproduced. With similar degrees of hyperglycemia in obese mice of these strains, the haplotype at chromosome 5 is associated with β-cell mass and circulating insulin concentrations. Finally, we offer arguments that production of multiple incipient congenic lines is an economical alternative to the production of speed congenic strains.

Original languageEnglish (US)
Pages (from-to)2287-2295
Number of pages9
JournalEndocrinology
Volume147
Issue number5
DOIs
StatePublished - May 2006

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Leptin Receptors
Chromosomes, Human, Pair 5
Hyperglycemia
Insulin Resistance
Obese Mice
Hyperinsulinism
Leptin
Genetic Crosses
Modifier Genes
Type 2 Diabetes Mellitus
Haplotypes
Genome
Insulin
Phenotype

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Allelic variation on chromosome 5 controls β-cell mass expansion during hyperglycemia in leptin receptor-deficient diabetes mice. / Luo, Na; Shun, Mei Liu; Liu, Hong; Li, Qiong; Xu, Qun; Sun, Xi; Davis, Brandi; Li, Jing; Chua, Jr., Streamson C.

In: Endocrinology, Vol. 147, No. 5, 05.2006, p. 2287-2295.

Research output: Contribution to journalArticle

Luo, Na ; Shun, Mei Liu ; Liu, Hong ; Li, Qiong ; Xu, Qun ; Sun, Xi ; Davis, Brandi ; Li, Jing ; Chua, Jr., Streamson C. / Allelic variation on chromosome 5 controls β-cell mass expansion during hyperglycemia in leptin receptor-deficient diabetes mice. In: Endocrinology. 2006 ; Vol. 147, No. 5. pp. 2287-2295.
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