| First Author | Tudurí E | Year | 2014 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 306 |
| Issue | 7 | Pages | E748-55 |
| PubMed ID | 24473435 | Mgi Jnum | J:211592 |
| Mgi Id | MGI:5575712 | Doi | 10.1152/ajpendo.00681.2013 |
| Citation | Tuduri E, et al. (2014) Partial ablation of leptin signaling in mouse pancreatic alpha-cells does not alter either glucose or lipid homeostasis. Am J Physiol Endocrinol Metab 306(7):E748-55 |
| abstractText | The role of glucagon in the pathological condition of diabetes is gaining interest, and it has been recently reported that its action is essential for hyperglycemia to occur. Glucagon levels, which are elevated in some diabetic models, are reduced following leptin therapy. Likewise, hyperglycemia is corrected in type 1 diabetic mice treated with leptin, although the mechanisms have not been fully determined. A direct inhibitory effect of leptin on mouse and human alpha-cells has been demonstrated at the levels of electrical activity, calcium signaling, and glucagon secretion. In the present study we employed the Cre-loxP strategy to generate Lepr(flox/flox) Gcg-cre mice, which specifically lack leptin receptors in glucagon-secreting alpha-cells, to determine whether leptin resistance in alpha-cells contributes to hyperglucagonemia, and also whether leptin action in alpha-cells is required to improve glycemia in type 1 diabetes with leptin therapy. Immunohistochemical analysis of pancreas sections revealed Cre-mediated recombination in approximately 43% of the alpha-cells. We observed that in vivo Lepr(flox/flox) Gcg-cre mice display normal glucose and lipid homeostasis. In addition, leptin administration in streptozotocin-induced diabetic Lepr(flox/flox) Gcg-cre mice restored euglycemia similarly to control mice. These findings suggest that loss of leptin receptor signaling in close to one-half of alpha-cells does not alter glucose metabolism in vivo, nor is it sufficient to prevent the therapeutic action of leptin in type 1 diabetes. |
