| First Author | Clee SM | Year | 2005 |
| Journal | Am J Ther | Volume | 12 |
| Issue | 6 | Pages | 491-8 |
| PubMed ID | 16280642 | Mgi Jnum | J:106121 |
| Mgi Id | MGI:3617592 | Doi | 10.1097/01.mjt.0000178781.89789.25 |
| Citation | Clee SM, et al. (2005) Genetic and genomic studies of the BTBR ob/ob mouse model of type 2 diabetes. Am J Ther 12(6):491-8 |
| abstractText | The BTBR mouse strain harbors alleles promoting insulin resistance. When made genetically obese (ob/ob), these mice develop severe type 2 diabetes (fasting glucose >400 mg/dL). By contrast, C57BL/6 ob/ob mice are able to compensate for the obesity-induced insulin resistance by increasing pancreatic insulin secretion and thus maintain only slightly elevated plasma glucose levels (<250 mg/dL). Islet insulin secretory responses to glucose are undiminished in the remaining islets of BTBR ob/ob mice. A genome-wide linkage analysis identified 3 major loci influencing plasma glucose and/or insulin levels in an F2ob/ob sample derived from the 2 strains. A locus on chromosome 2 affects insulin sensitivity and is independent of obesity. Loci on chromosomes 16 and 19 affect fasting glucose and insulin levels and likely affect beta-cell mass or function. Analysis of mRNA expression patterns revealed a reduction in lipogenic gene expression in adipose tissue associated with obesity. Conversely, hepatic lipogenic gene expression increases in obese mice, but to a much greater extent in the diabetes-resistant C57BL/6 strain. We propose that hepatic lipogenic capacity affects susceptibility to obesity-induced diabetes. |
