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Current Trends in Endocrinology   Volumes    Volume 7 
Renal glucose handling and the kidney as a target to anti-diabetic medication
Eugenio Cersosimo
Pages: 81 - 94
Number of pages: 14
Current Trends in Endocrinology
Volume 7 

Copyright © 2014 Research Trends. All rights reserved

In this article a review of the fundamental concepts behind the normal physiology and the adaptation of glucose handling by the kidney in diabetes mellitus is provided. The main objective is a wide and comprehensive discussion of the events leading to the development of a new class of anti-hyperglycemic agents that act primarily by chemical inhibition of tubular glucose reabsorption. Relevant molecular pathways and transport systems involved in renal glucose kinetics and metabolism are described. The process of glomerular ultrafiltration with complete proximal tubular reabsorption of glucose is discussed in detail, together with the contribution to systemic glucose homeostasis of renal gluconeogenesis and glucose utilization. The “maladaptive” changes that occur in the tubular reabsorptive capacity in patients with diabetes mellitus, which lead to increased rates of glucose re-entry into the circulation, thus perpetuating the hyperglycemia are analyzed. With a brief historical perspective, the development and expansion of these new anti-diabetic agents, which are capable of lowering blood glucose by blocking the activity of the sodium-glucose co-transporters in the kidney, are examined. Finally, results of some critical pharmacological and pre-clinical investigational studies, as well as clinical efficacy and safety data available for the current sodium-glucose transporter 2 (SGLT-2) inhibitors are analyzed in detail. In conclusion, some suggestions as to the best patient profile and clinical conditions in which these anti-diabetic agents are more likely to be beneficial are proposed.
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