To determine whether previous renal injury accelerates the progression of glomerulosclerosis and interstitial fibrosis, we examined the effect of treating rats with angiotensin II after Habu venom injury. After initiating disease, we examined the origin of interstitial myofibroblasts by locating ␣-smooth muscle actin (␣-SMA)-positive and Na

These studies demonstrate that a variety of receptor signaling pathways are activated in the renal cortex of mice with type 2 diabetes, and suggest a role for augmented insulin receptor activity in nephropathy of type 2 diabetes.

Background Heart failure (HF) is associated with high rates of hospitalizations, morbidity, mortality, and costs. Remote patient monitoring (mobile health, mHealth) shows promise in improving self-care and HF management, thus increasing quality of care while reducing hospitalizations and costs; however, limited information exists regarding perceptions of older adults with HF about mHealth use. Objective This study aimed to compare perspectives of older adults with HF who were randomized to either (1) mHealth equipment connected to a 24-hour call center, (2) digital home equipment, or (3) standard care, with regard to ease and satisfaction with equipment, provider communication and engagement, and ability to self-monitor and manage their disease. Methods We performed a pilot study using a mixed-methods descriptive design with pre- and postsurveys, following participants for 12 weeks. We augmented these data with semistructured qualitative interviews to learn more about feasibility, satisfaction, communication, and self-management. Results We enrolled 28 patients with HF aged 55 years and above, with 57% (16/28) male, 79% (22/28) non-Hispanic white, and with multiple comorbid conditions. At baseline, 50% (14/28) rated their health fair or poor and 36% (10/28) and 25% (7/28) were very often/always frustrated and discouraged by their health. At baseline, 46% (13/28) did not monitor their weight, 29% (8/28) did not monitor their blood pressure, and 68% (19/28) did not monitor for symptoms. Post intervention, 100% of the equipment groups home monitored daily. For technology anxiety, 36% (10/28) indicated technology made them nervous, and 32% (9/28) reported fear of technology, without significant changes post intervention. Technology usability post intervention scored high (91/100), reflecting ease of use. A majority indicated that a health care provider should be managing their health, and 71% reported that one should trust and not question the provider. Moreover, 57% (16/28) believed it was better to seek professional help than caring for oneself. Post intervention, mHealth users relied more on themselves, which was not mirrored in the home equipment or standard care groups. Participants were satisfied with communication and engagement with providers, yet many described access problems. Distressing symptoms were unpredictable and prevailed over the 12 weeks with 79 provider visits and 7 visits to emergency departments. The nurse call center received 872 readings, and we completed 289 telephone calls with participants. Narrative data revealed the following main themes: (1) traditional communication and engagement with providers prevailed, delaying access to care; (2) home monitoring with technology was described as useful, and mHealth users felt secure knowing that someone was observing them; (3) equipment groups felt more confident in self-monitoring and managing; and finally, (4) uncertainty and frustration with ...

Interaction between angiotensin II, which binds a G-protein-coupled receptor, and insulin, a ligand for receptor tyrosine kinase, was examined in renal proximal tubular epithelial cells. Augmented protein translation by insulin involves activation of eukaryotic initiation factor 4E (eIF4E) which follows the release of the factor from a heterodimeric complex by phosphorylation of its binding protein, 4E-BP1. Angiotensin II (1 nM) or insulin (1 nM) individually stimulated 4E-BP1 phosphorylation. However, pre-incubation with angiotensin II abrogated insulin-induced phosphorylation of 4E-BP1, resulting in persistent binding to eIF4E. Although angiotensin II and insulin individually activated phosphoinositide 3-kinase and extracellular signal-regulated kinase (ERK)-1/-2-type mitogen-activated protein (MAP) kinase, pre-incubation with angiotensin II abolished insulin-induced stimulation of these kinases, suggesting more proximal events in insulin signalling may be intercepted. Pretreatment with angiotensin II markedly inhibited insulin-stimulated tyrosine phosphorylation of insulin-receptor beta-chain and insulin-receptor substrate 1. Losartan prevented angiotensin II inhibition of insulin-induced ERK-1/-2-type MAP kinase activation and 4E-BP1 phosphorylation, suggesting mediation of the effect of angiotensin II by its type 1 receptor. Insulin-stimulated de novo protein synthesis was also abolished by pre-incubation with angiotensin II. These data show that angiotensin II inhibits 4E-BP1 phosphorylation and stimulation of protein synthesis induced by insulin by interfering with proximal events in insulin signalling. Our data provide a mechanistic basis for insulin insensitivity induced by angiotensin II.