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Diabetes is a complex, chronic medical condition affecting 29.1 million people in the United States (9.3% of the population) and is projected to affect one in three Americans by 2050 if the current trend continues (1). Diabetes management can be challenging, often requiring multiple therapeutic agents as the disease progresses. Current guidelines recommend metformin as first-line pharmacological therapy for the treatment of type 2 diabetes. Multiple second-line options are available for patients whose A1C goal is not achieved with monotherapy, and selection should be based on patient- and drug-specific factors. Sodium–glucose cotransporter 2 (SGLT2) inhibitors, the newest U.S. Food and Drug Administration (FDA)–approved oral antidiabetic agents, are among these options for patients with type 2 diabetes. Canagliflozin, dapagliflozin, and empagliflozin are the currently available SGLT2 inhibitors in the United States (2,3). Sodium–glucose cotransporter 1 (SGLT1) is predominantly located in the small intestine, but is also expressed in the kidneys, trachea, heart, and colon (4,5). In the kidneys, SGLT1 is primarily located in the S3 segment of the proximal convoluted tubule (PCT) (4). SGLT2 is expressed in the kidneys and primarily located in the S1 and S2 segments of the PCT (4,5). In normoglycemic adults, about 180 g of glucose (Figure 1) is filtered per day in the glomerulus, and most is reabsorbed (4,6). In people with diabetes, reabsorption of glucose is increased compared to people without diabetes (7,8). SGLT1 and SGLT2 are located in the apical membrane and facilitate the transport of glucose with sodium from the renal tubular lumen into the cells (Figure 2) (4). FIGURE 1. Structures of glucose, phlorizin, canagliflozin, dapagliflozin, and empagliflozin. FIGURE 2. Cotransport of glucose and sodium by SGLT1 and SGLT2 in the PCT. Phlorizin (Figure 1), an O -glucose derivative/ O -glycoside, was discovered in …

Borrelia burgdorferi , the agent of Lyme disease, responds to numerous host-derived signals to alter adaptive capabilities during its enzootic cycle in an arthropod vector and mammalian host. Molecular mechanisms that enable B. burgdorferi to detect, channel, and respond to these signals have become an intense area of study for developing strategies to limit transmission/infection. Bioinformatic analysis of the borrelial genome revealed the presence of polyamine transport components (PotA, PotB, PotC, and PotD), while homologs for polyamine biosynthesis were conspicuously absent. Although potABCD is cotranscribed, the level of PotA was elevated under in vitro growth conditions mimicking unfed ticks compared to the level in fed ticks, while the levels of PotD were similar under the aforementioned conditions in B. burgdorferi . Among several polyamines and polyamine precursors, supplementation of spermine or spermidine in the borrelial growth medium induced synthesis of major regulators of gene expression in B. burgdorferi , such as RpoS and BosR, with a concomitant increase in proteins that contribute to colonization and survival of B. burgdorferi in the mammalian host. Short transcripts of rpoS were elevated in response to spermidine, which was correlated with increased protein levels of RpoS. Transcriptional analysis of rpoZ and B. burgdorferi rel ( rel Bbu ; bb0198 ) in the presence of spermidine revealed the interplay of multiple regulatory factors in B. burgdorferi gene expression. The effect of spermidine on the levels of select borrelial proteins was also influenced by serum factors. These studies suggest that multiple host-derived signals/nutrients and their transport systems contribute to B. burgdorferi adaptation during the vector and vertebrate host phases of infection.