A Randomized Crossover Trial of Mixed Meal Tolerance Test Response in People with Type 1 Diabetes on Insulin Pump Therapy and YG1699 or Dapagliflozin.

YG1699 is a novel inhibitor of sodium-glucose cotransporter 1 (SGLT1) and SGLT2. This double-blind, 3-way crossover trial compared YG1699 to dapagliflozin as an adjunct to insulin in people with type 1 diabetes (T1D) on insulin pump therapy. Treatment periods included four mixed meal tolerance tests (MMTTs) and insulin withdrawal tests per person. Nineteen adults with T1D were randomized to YG1699 10 mg, YG1699 25 mg, and dapagliflozin 10 mg once daily for 1 week in different orders. The primary end point was the difference in area under the curve (AUC) in plasma glucose (AUC0-120min) after an MMTT between treatment groups. Mean change in plasma glucose after an MMTT (AUC0-120min) was lower for YG1699 10 mg vs. dapagliflozin (89.51% of baseline vs. 102.13%, 90% confidence interval (CI) vs. dapagliflozin, -6% to -16%, P = 0.0003) and for YG1699 25 mg (84.83% vs. 102.13%, 90% CI vs. dapagliflozin -13% to -22%, P < 0.0001). At 120 minutes, mean glucose values on no treatment, dapagliflozin, YG1699 10 mg, and YG1699 25 mg were 149 (SE 7.6), 141 (SE 6.1), 128 (SE 6.9), and 115 (SE 7.8) mg/dL, respectively. Insulin dose requirements were lower for YG1699 10 mg and 25 mg vs. dapagliflozin for bolus insulin, and for YG1699 10 mg vs. dapagliflozin for total daily insulin. Safety profiles were similar between treatment groups. YG1699 reduced post-prandial glucose more than dapagliflozin in people with T1D on insulin pump therapy. The results were consistent with dual SGLT1/SGLT2 inhibition by YG1699.

[Studies on the spectral characteristics of efficient HIV-1 fusion inhibitor C22].

Acquired immune deficiency syndrome (AIDS) is increasing its negative influences on human society and economy. In the present paper, HIV-1 cell fusion peptide inhibitor C22 was expressed and purified based on the C-terminal sequence of HIV-1 membrane fusion glycoprotein gp41. The gene coding for C22 was totally synthesized using gp41 gene as a template and amplified by PCR The cloned C22 gene was confirmed by restriction endonuclease and sequence analysis and then cloned into plasmid pTMHa30-51. The prepared plasmid was transformed into E. coli BL21 (DE3) and the expressing products were analyzed on SDS-PAGE and tested with mass spectrum. The results indicated that C22 showed high HIV-1 fusion inhibiting capacity, meanwhile, with good thermal stability and water-solubility, and showed no cell toxicity in tested concentrations. The spectral characteristics were tested with circular dichroism (CD). When treated at different temperature in solution condition, the content of a helix of C22 increased at 37 degrees C while decreased sharply at 80 degrees C. The peak value changed significantly with different pH values. The content of a helix of C22 decreased as pH varied toward acid and alkali and the random coiling increased, which led to a relaxed structure. This result indicated that the C22 structure is stable with pH 6. This research may provide a theoretic foundation for the new type HIV-1 peptide inhibitor designing and spectral characteristics study.