SUMMARY The human growth hormone (hGH) minigene is frequently used in the derivation of transgenic mouse lines to enhance transgene expression. Although this minigene is present in the transgenes as a second-cistron, and thus not thought to be expressed, we found that three commonly used lines, Pdx1-CreLate, RIP-Cre, and MIP-GFP, each expressed significant amounts of hGH in pancreatic islets. Locally secreted hGH binds to prolactin receptors on β cells, activates STAT5 signaling, and induces pregnancy-like changes in gene expression, thereby augmenting pancreatic β cell mass and insulin content. In addition, islets of Pdx1-CreLate mice have lower GLUT2 expression and reduced glucose-induced insulin release and are protected against the β cell toxin streptozotocin. These findings may be important when interpreting results obtained when these and other hGH minigene-containing transgenic mice are used.

Background:The diabetogenic agent streptozotocin (STZ) induces direct kidney injury, which is a setback in diabetic nephropathy (DN) research. Results: The Sglt inhibitor phlorizin reduces STZ uptake and hence toxicity in the kidneys. Conclusion: In the kidney, STZ toxicity is mediated by Sglts. Significance: Using the proposed STZ regimen, researchers can now induce DN without direct damage to proximal tubuli.