Renal glucose transporters: an insulin-independent pathway

The body handles excess glucose through both insulin-independent and insulin-dependent mechanisms.1

One example of an insulin-independent mechanism is reabsorption of glucose from urinary filtrate and the role of sodium-glucose cotransporters (SGLTs) and glucose transporters (GLUTs).1-3

* Approximately 90% of glucose is reabsorbed in the S1 segment of the proximal tubule, where SGLT2 and GLUT2 are located3

* The remaining glucose (approximately 10%) is reabsorbed in the S3 segment of the proximal tubule, where SGLT1 and GLUT1 are located3

Examples of insulin-dependent mechanisms include:

* In muscle and adipose tissue, insulin binding to insulin receptors promotes the appearance on the cell membrane of GLUT4 molecules, facilitating the uptake of glucose into the cells4

* In the liver, insulin regulates blood glucose levels by suppressing hepatic glucose output and increasing postprandial glucose storage in the form of glycogen5

* In adipose tissue, insulin helps in the synthesis and storage of excess glucose in the form of triglycerides5

The body's ability to handle excess glucose in patients with diabetes is impaired compared with nondiabetic individuals.5 In type 2 diabetes, lifestyle changes, including diet and exercise, are essential for helping to control excess glucose levels. Patients with type 2 diabetes may find it challenging, however, to maintain these changes.6-9

Approximately 26 million adults in the United States have diabetes; surveys of patients with diabetes
have shown10,a:

* About 43% are not achieving glycated hemoglobin (HbA1c) goals of <7%11,b,c
* 67% have hypertension10,a,b
* 54% have hypercholesterolemia11,b,c
* 55% are obese12,b,d

Type 2 diabetes—a chronic, progressive disease characterized by hyperglycemia and associated with multiple comorbidities—is epidemic and growing in the United States.13-15

a Estimates based on 2005-2008 National Health and Nutrition Examination Survey (NHANES), and 2010 US resident population estimates.10 b All percentages approximate. c Data from NHANES 2003-2004.11 d Data from NHANES 1999-2002.12


References:
1. DeFronzo RA. Med Clin North Am. 2004;88(4):787-835.
2. Marsenic O. Am J Kidney Dis. 2009;53(5):875-883.
3. Rahmoune H, Thompson PW, Ward JM, Smith CD, Hong G, Brown J. Diabetes. 2005;54(12):3427-3434.
4. Uldry M, Thorens B. Eur J Physiol. 2004;447(5):480-489.
5. Guyton AC. Textbook of Medical Physiology. 7th ed. Philadelphia, PA: WB Saunders Company; 1986.
6. Boulé NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. JAMA. 2001;286(10):1218-1227.
7. Marwick TH, Hordern MD, Miller T, et al. Circulation. 2009;119(25):3244-3262.
8. Sigal RJ, Kenny GP, Boulé NG, et al. Ann Intern Med. 2007;147(6):357-369.
9. Zhao G, Ford ES, Li C, Mokdad AH. Diabet Med. 2008;25(2):221-227.
10. Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, 2011.
11. Ong KL, Cheung BMY, Wong LYF, Wat NMS, Tan KCB, Lam KSL. Ann Epidemiol. 2008;18(3):222-229.
12. Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report (MMWR) Web site. Prevalence of Overweight and Obesity Among Adults with Diagnosed Diabetes --- United States, 1988--1994 and 1999--2002. Accessed January 31, 2011.
13. American Association of Clinical Endocrinologists (AACE) Diabetes Mellitus Clinical Practice Guidelines Task Force. American Association of Clinical Endocrinologists. Accessed January 31, 2011.
14. American Diabetes Association. Diabetes Care. 2011;34(suppl 1):S62-S69.
15. National Institutes of Health. Updated June 2008. http://www.nih.gov/about/researchres...e2Diabetes.pdf. Accessed January 31, 2011.