ArticleEndocrinology2007
Tissue kallikrein reverses insulin resistance and attenuates nephropathy in diabetic rats by activation of phosphatidylinositol 3-kinase/protein kinase B and adenosine 5'-monophosphate-activated protein kinase signaling pathways.
Article in Endocrinology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 49 citations in OpenAlex.
- G-Protein-Coupled Receptors in Chronic Kidney Disease Induced by Hypertension and Diabetes.Cells · 2025Review
- A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats.Cell genomics · 2024Article
- A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats.bioRxiv : the preprint server for biology · 2023Article
- Decreased Tissue Kallikrein Levels and the Risk of Ischemic Stroke: A Community-Based Cross-Sectional Study in China.Journal of inflammation research · 2022Article
- Ameliorative Effects of Oral Glucosamine on Insulin Resistance and Pancreatic Tissue Damage in Experimental Wistar rats on a High-fat Diet.Comparative medicine · 2021Article
- Good or bad: Application of RAAS inhibitors in COVID-19 patients with cardiovascular comorbidities.Pharmacology & therapeutics · 2020Review
- Article
- Effect of personalized moderate exercise training on Wistar rats fed with a fructose enriched water.Nutrition & metabolism · 2018Article
- Metabolic Syndrome and Hypertension Resulting from Fructose Enriched Diet in Wistar Rats.BioMed research international · 2017Article
- Acupuncture Alters Expression of Insulin Signaling Related Molecules and Improves Insulin Resistance in OLETF Rats.Evidence-based complementary and alternative medicine : eCAM · 2016Article
- Progressive Induction of Type 2 Diabetes: Effects of a Reality-Like Fructose Enriched Diet in Young Wistar Rats.PloS one · 2016Article
- Pharmacological effects of recombinant human tissue kallikrein on bradykinin B2 receptors.Pharmacology research & perspectives · 2015Article
- Renal kallikrein activation and renoprotection after dual blockade of renin-angiotensin system in diet-induced diabetic nephropathy.Journal of diabetes research · 2015Article
- Tissue Kallikrein Activity, Detected by a Novel Method, May Be a Predictor of Recurrent Stroke: A Case-Control Study.Disease markers · 2015Article
- Differential proteomic analysis of the pancreas of diabetic db/db mice reveals the proteins involved in the development of complications of diabetes mellitus.International journal of molecular sciences · 2014Article
- Preclinical characterization of recombinant human tissue kallikrein-1 as a novel treatment for type 2 diabetes mellitus.PloS one · 2014Article
- Autoimmune diabetes is suppressed by treatment with recombinant human tissue Kallikrein-1.PloS one · 2014Article
- Relation of plasma tissue kallikrein levels to presence and severity of coronary artery disease in a Chinese population.PloS one · 2014Article
- The kallikrein-kinin system in diabetic nephropathy.Kidney international · 2012Review
- Tyrosines 868, 966, and 972 in the kinase domain of JAK2 are autophosphorylated and required for maximal JAK2 kinase activity.Molecular endocrinology (Baltimore, Md.) · 2010Article
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Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
We previously reported that iv delivery of the human tissue kallikrein (HK) gene reduced blood pressure and plasma insulin levels in fructose-induced hypertensive rats with insulin resistance. In the current study, we evaluated the potential of a recombinant adeno-associated viral vector expressing the HK cDNA (rAAV-HK) as a sole, long-term therapy to correct insulin resistance and prevent renal damage in streptozotocin-induced type-2 diabetic rats. Administration of streptozotocin in conjunction with a high-fat diet induced systemic hypertension, diabetes, and renal damage in rats. Delivery of rAAV-HK resulted in a long-term reduction in blood pressure, and fasting plasma insulin was significantly lower in the rAAV-HK group than in the control group. The expression of phosphatidylinositol 3-kinase p110 catalytic subunit and the levels of phosphorylation at residue Thr-308 of Akt, insulin receptor B, and AMP-activated protein kinases were significantly decreased in organs from diabetic animals. These changes were significantly attenuated after rAAV-mediated HK gene therapy. Moreover, rAAV-HK significantly decreased urinary microalbumin excretion, improved creatinine clearance, and increased urinary osmolarity. HK gene therapy also attenuated diabetic renal damage as assessed by histology. Together, these findings demonstrate that rAAV-HK delivery can efficiently attenuate hypertension, insulin resistance, and diabetic nephropathy in streptozotocin-induced diabetic rats.
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