| First Author | Cordoba-Chacon J | Year | 2014 |
| Journal | Endocrinology | Volume | 155 |
| Issue | 3 | Pages | 726-35 |
| PubMed ID | 24424062 | Mgi Jnum | J:208804 |
| Mgi Id | MGI:5565051 | Doi | 10.1210/en.2013-1825 |
| Citation | Cordoba-Chacon J, et al. (2014) Long- but not short-term adult-onset, isolated GH deficiency in male mice leads to deterioration of beta-cell function, which cannot be accounted for by changes in beta-cell mass. Endocrinology 155(3):726-35 |
| abstractText | Developmental models of GH deficiency (GHD) and excess indicate that GH is positively associated with beta-cell mass. Therefore, the reduction in GH levels observed with age and weight gain may contribute to the age-related decline in beta-cell function. To test this hypothesis, beta-cell mass and function were assessed in a mouse model of adult-onset, isolated GHD (AOiGHD). beta-Cell mass did not differ between low-fat (LF)-fed AOiGHD and controls. However, high fat-fed AOiGHD mice displayed impaired expansion of beta-cell mass and a reduction of bromodeoxyuridine-labeled islet cells, whereas in vitro beta-cell function (basal and glucose-stimulated insulin secretion [GSIS]) did not differ from controls. In contrast, duration of AOiGHD differentially altered in vitro beta-cell function in LF-fed mice. Specifically, islets from young LF-fed AOiGHD mice showed significant reductions in insulin content and basal insulin secretion, but GSIS was similar to that of controls. A similar islet phenotype was observed in a developmental model of isolated GHD (GH-releasing hormone knockout). Given that LF- and high fat-fed AOiGHD mice, as well as GH-releasing hormone knockout mice, display improved insulin sensitivity, islet changes may be due to reduced insulin demand, rather than primary beta-cell dysfunction. However, islets from older LF-fed AOiGHD mice exhibited impaired GSIS, associated with reduced expression of genes important to maintain glucose sensing, suggesting that factors secondary to AOiGHD can alter beta-cell function with age. AOiGHD mice exhibited postprandial hypertriglyceridemia and increased pancreatic expression of lipid/inflammatory stress response genes (activating transcription factor 3 and peroxisome proliferator activator receptor beta/delta). Therefore, we speculate that these changes may initially protect the AOiGHD beta-cell, but with age, lipotoxicity may impair beta-cell function. |
