Niloofar Tabatabai, PhD
Associate Professor of Medicine and Physiology
Department of Medicine
Division of Endocrinology, Metabolism, and Clinical Nutrition
Kidney Disease Center
The focus of my research is molecular expression of kidney sodium-glucose cotransporters, SGLT1, SGLT2, and SGLT3. Normally, glucose is filtered freely through kidney's glomerulus but then it is reabsorbed back to the blood by glucose transporters. While glucose diffuses through GLUT transporters, it is co-transported with sodium by SGLTs. SGLT2 is considered the major sodium-glucose transporter in the kidney and mutation in its gene has been associated with symptom of Familial Glucosuria in human. SGLT1 is also a sodium-glucose transporter but it plays a minor role in the absorption of glucose in the kidney. On the other hand, SGLT1 is considered intestine's major glucose transporter and symptoms of Glucose-Galactose Malabsorption with mild glucosuria in humans have been linked to mutations in its gene. While SGLT3 has high degree of amino acid sequence homology to SGLT1 and SGLT2, human SGLT3 has been suggested to be a glucose sensor and a sodium transporter. Role of SGLT3 in the kidney has not been investigated.
Several projects in my laboratory address changes in normal expression of kidney SGLTs. Chronic exposure to the environmental toxicant, heavy metal cadmium, can cause symptom of glucosuria. First, by using a cell culture model to investigate the molecular mechanism of cadmium-induced glucosuria, we have been able to show that exposure of kidney cells to cadmium resulted in a decrease in glucose uptake and this decrease correlated with declines in mRNA levels of SGLT1 and SGLT2. We have identified transcription factor Sp1, a zinc finger protein, as a mediator of the cadmium-induced down-regulation of SGLT1 and 2 expressions. We are currently investigating the signal transduction pathway that may be involved. Second, we are studying the transcriptional events leading to alterations in renal expression of SGLTs in response to type 2 diabetes. Third, we showed for the first time that SGLT3 mRNA was expressed in the whole kidney. Currently, we are investigating the localization and functional role of SGLT3 in the kidney. The aim of the above studies is to better understand the molecular pathways that are involved in expression of kidney SGLTs and to identify the role of new member of SGLT family of transporters.
Enhanced expressions of sodium–glucose cotransporters in the kidneys of diabetic Zucker rats. Niloofar M. Tabatabai, Mukut Sharma, Samuel S. Blumenthal, David H. Petering. Diabetes, 4372 1–4, 2008.
Zinc binding ligands and cellular zinc trafficking: Apo-metallothionein, glutathione, TPEN, proteomic zinc, and Zn-Sp1. Ujala Rana, Rajendra Kothinti, Jeffrey Meeusen, Niloofar M. Tabatabai, Susan Krezoski, David H. Petering. Journal of Inorganic Biochemistry 102 (2008) 489–499.