RGD Reference Report - 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. - Rat Genome Database

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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.

Authors: Yuan, G  Deng, J  Wang, T  Zhao, C  Xu, X  Wang, P  Voltz, JW  Edin, ML  Xiao, X  Chao, L  Chao, J  Zhang, XA  Zeldin, DC  Wang, DW 
Citation: Yuan G, etal., Endocrinology. 2007 May;148(5):2016-26. Epub 2007 Feb 1.
RGD ID: 1641794
Pubmed: PMID:17272402   (View Abstract at PubMed)
PMCID: PMC2084357   (View Article at PubMed Central)
DOI: DOI:10.1210/en.2006-0602   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
KLK1HumanDiabetic Nephropathies  IDA  RGD 
Klk1c12RatDiabetic Nephropathies  ISOKLK1 (Homo sapiens) RGD 
KLK1Humanhypertension  IDA  RGD 
Klk1c12Rathypertension  ISOKLK1 (Homo sapiens) RGD 
KLK1HumanInsulin Resistance  IDA  RGD 
Klk1c12RatInsulin Resistance  ISOKLK1 (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Klk1c12  (kallikrein 1-related peptidase C12)

Genes (Homo sapiens)
KLK1  (kallikrein 1)

Objects referenced in this article
Gene PIK3CG phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma Homo sapiens
Gene Pik3cg phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma Mus musculus
Gene Pik3cg phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma Rattus norvegicus

Additional Information