| First Author | Tiwari S | Year | 2013 |
| Journal | J Am Soc Nephrol | Volume | 24 |
| Issue | 8 | Pages | 1209-14 |
| PubMed ID | 23723425 | Mgi Jnum | J:338281 |
| Mgi Id | MGI:6868245 | Doi | 10.1681/ASN.2012060628 |
| Citation | Tiwari S, et al. (2013) Deletion of the insulin receptor in the proximal tubule promotes hyperglycemia. J Am Soc Nephrol 24(8):1209-14 |
| abstractText | Nearly all renal tubular epithelial cells express insulin receptor. The insulin receptor in the distal tubule appears to modulate BP, but the role of the insulin receptor in the proximal tubule is unknown. Here, we selectively knocked out the insulin receptor from the proximal tubules of mice. Western blotting confirmed a two- to three-fold reduction in renal cortical homogenate insulin receptor-beta among knockout mice compared with wild-type littermates. Young knockout mice exhibited a mildly diabetic phenotype, evidenced by higher fasting plasma glucose levels than wild-type mice. Assessments by hyperinsulinemic-euglycemic clamp and a glucose tolerance test revealed no differences in insulin sensitivity or overt pancreatic function, respectively. Renal cortical mRNA expression and enzyme activity of glucose-6-phosphatase, which catalyzes the final step of glucose production, were significantly higher in knockout mice. Taken together, these results support a role for insulin receptor in the proximal tubule in the modulation of systemic glucose levels. Downregulation of the insulin receptor in the proximal tubule, which occurs in insulin-resistant states, may promote hyperglycemia through enhanced gluconeogenesis. |
