Journal article
Probing SGLT2 as a therapeutic target for diabetes: Basic physiology and consequences
Diabetes and Vascular Disease Research, Vol.12(2), pp.78-89
2015
PMCID: PMC5886707
PMID: 25616707
Abstract
Traditional treatments for type 1 and type 2 diabetes are often associated with side effects, including weight gain and hypoglycaemia that may offset the benefits of blood glucose lowering. The kidneys filter and reabsorb large amounts of glucose, and urine is almost free of glucose in normoglycaemia. The sodium-dependent glucose transporter (SGLT)-2 in the early proximal tubule reabsorbs the majority of filtered glucose. Remaining glucose is reabsorbed by SGLT1 in the late proximal tubule. Diabetes enhances renal glucose reabsorption by increasing the tubular glucose load and the expression of SGLT2 (as shown in mice), which maintains hyperglycaemia. Inhibitors of SGLT2 enhance urinary glucose excretion and thereby lower blood glucose levels in type 1 and type 2 diabetes. The load-dependent increase in SGLT1-mediated glucose reabsorption explains why SGLT2 inhibitors in normoglycaemic conditions enhance urinary glucose excretion to only similar to 50% of the filtered glucose. The role of SGLT1 in both renal and intestinal glucose reabsorption provides a rationale for the development of dual SGLT1/2 inhibitors. SGLT2 inhibitors lower blood glucose levels independent of insulin and induce pleiotropic actions that may be relevant in the context of lowering cardiovascular risk. Ongoing long-term clinical studies will determine whether SGLT2 inhibitors have a safety profile and exert cardiovascular benefits that are superior to traditional agents.
Details
- Title
- Probing SGLT2 as a therapeutic target for diabetes: Basic physiology and consequences
- Authors
- Linda A. Gallo (Corresponding Author) - University of QueenslandErnest M. Wright (Author) - Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USAVolker Vallon (Author) - University of California, San Diego
- Publication details
- Diabetes and Vascular Disease Research, Vol.12(2), pp.78-89
- Publisher
- Sage Publications Ltd.
- DOI
- 10.1177/1479164114561992
- ISSN
- 1752-8984
- PMID
- 25616707; PMC5886707
- Organisation Unit
- University of the Sunshine Coast, Queensland; School of Health and Behavioural Sciences - Legacy; School of Health - Biomedicine
- Language
- English
- Record Identifier
- 99679194502621
- Output Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web Of Science research areas
- Endocrinology & Metabolism
- Peripheral Vascular Disease
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Source: InCites