We observed that this primer/probe set essentially mirrors the data obtained with the primer/probe set spanning the junction of exons 6 and 7, as well as primer/probe sets spanning the exons 12, 45, and 910
We observed that this primer/probe set essentially mirrors the data obtained with the primer/probe set spanning the junction of exons 6 and 7, as well as primer/probe sets spanning the exons 12, 45, and 910. sodium-dependent amino acid transporter (SAAT1), and SGLT4 are highly abundant in small Mutant IDH1-IN-4 intestine and skeletal muscle; SGLT6 is expressed in the central nervous system; and sodium myoinositol cotransporter is ubiquitously expressed across all human tissues. == Electronic Supplementary Material == Supplementary material is available for this article at 10.1007/s13300-010-0006-4 and is accessible for authorized users. Keywords:quantitative PCR, SGLT2, sodium-glucose cotransporter protein, tissue expression, type 2 diabetes == Introduction == As a worldwide medical and economic problem type 2 diabetes is expanding internationally. The International Diabetes Federation Mutant IDH1-IN-4 estimates that in 2010 2010 approximately 285 million individuals have type 2 diabetes across the world; 1this number is expected to expand to 439 million individuals by 2030. Diabetes imposes a significant health and economic burden, and factoring in the additional costs of undiagnosed diabetes, prediabetes, and gestational diabetes, the total cost of diabetes in the US in 2007 amounted to $218 billion.2Despite the availability of several oral and injectable therapies for type 2 diabetes, there remains significant unmet medical need in this disease, justifying the search for more efficacious and safe treatments that can prevent disease progression and protect patients from microvascular and macrovascular complications. Among the types of therapies under development, inhibitors of SGLT2 (for Sodium GLucose coTransporter protein 2) represent a promising new class.3,4 One consideration for choosing a molecular target for the identification of Mutant IDH1-IN-4 a new treatment of a chronic disease such as type 2 diabetes is the spectrum of tissues in which the target of interest is expressed. A molecular target with a ubiquitous pattern of expression could pose concerns related to the activities of agonists or antagonists to this target in a wide variety of tissues, whereas a molecular target expressed in a restricted number of tissues might suggest a more selective pharmacologic profile. We have evaluated the expression pattern of SGLT2 and related family members by quantitative reverse transcription real-time polymerase chain reaction (RT-PCR) methodology in order to better understand the potential impact of a selective SGLT2 inhibitor in vivo. There are more than 200 SGLT family members, including 12 human orthologs.5Based on sequence homology, these 12 SGLT family members can be divided into two subfamilies, as shown inTable 1. SGLT1, SGLT2, sodium-dependent amino acid transporter (SAAT1; also known as SGLT3), sodium myo-inositol cotransporter (SMIT), SGLT4, SGLT5, and SGLT6 belong to one subfamily, sharing between 45% and 70% protein sequence identity amongst themselves. Most of the members of this subfamily transport or bind sugar molecules. The five other solute carrier family 5A (SLC5A) family members Na+/I- symporter (NIS), sodium-dependent multivitamin transporter (SMVT), choline transporter (CHT), apical iodide transporter/sodium monocarboxylate cotransporter 1 (AIT/SMCT1), and SMCT2 form another subfamily. They share between 40% and 50% protein sequence identity amongst themselves; members of this latter subfamily are involved in the cotransport of sodium with other physiologically important molecules such as iodide, ascorbate, RGS19 biotin, pantothenate, lipoate, choline, and monocarboxylates such as lactate.5Since only 18% to 20% protein sequence identity exists between the two subfamilies, the focus of our studies was the sugar-binding class of SGLT cotransporters most closely related to SGLT2 (Table 1). The first sugar-binding SGLT sequence to be cloned, by Wright and colleagues, was the high-affinity sodium-glucose cotransporter SGLT1, which was found to be expressed in the small intestinal mucosa6and associated with glucose and galactose transport at that site. SGLT1 was later found to be expressed in many tissues across the body,7and mutations in SGLT1 were associated with the human genetic syndrome glucose-galactose malabsorption.8SGLT2 was cloned subsequently, and was characterized as a low-affinity sodium-glucose cotransporter expressed in the renal early proximal tubule.9,10SAAT1 was first cloned as a sodium-amino acid cotransporter11but was later found to have glucose cotransporter activity.12It was found in kidney, small intestine, and other tissues and is now suggested to be a sodium-dependent glucose sensor rather than a sodium-glucose cotransporter.13SMIT is an osmoregulatory sodium-inositol cotransporter found in many tissues including brain and cardiac myocytes.14,15SGLT4 is a.