Table II.
Group | Gr 1 | Gr 2 | Gr 3 | Gr 4 | Gr 5 | Gr 6 | Gr 7 | Gr 8 | |
---|---|---|---|---|---|---|---|---|---|
Non-FBG near the end of treatment, day 31 | mg/dl, mean | 136 | 608 | 619 | 599 | 497 | 536 | 414 | 640 |
SEM | 3 | 18 | 16 | 21 | 37 | 25 | 53 | 10 | |
p value versus Gr 2 | <0.0001 | ----- | 0.6549 | 0.7497 | 0.0173a | 0.0348a | 0.0038a | 0.1425 | |
Non-FBG gAUC during treatment, day 7–day 31 | mg/dl, mean | 3176 | 11614 | 12006 | 10863 | 9292 | 10526 | 8594 | 11266 |
SEM | 44 | 758 | 318 | 516 | 918 | 439 | 1059 | 743 | |
p value versus Gr 2 | <0.0001 | ----- | 0.6408 | 0.4265 | 0.0714 | 0.2346 | 0.0360a | 0.7479 | |
HbA1c during treatment, week4-week1 | Δ HbA1c %, mean | −0.4 | 2.0 | 2.4 | 1.8 | 1.1 | 1.6 | 0.9 | 2.2 |
SEM | 0.1 | 0.2 | 0.3 | 0.3 | 0.2 | 0.3 | 0.4 | 0.3 | |
p value versus Gr 2 | <0.0001 | ----- | 0.2860 | 0.5879 | 0.0067b | 0.2860 | 0.0275b | 0.5879 |
Omeprazole (Gr 5), Omeprazole+PGC-HBEGF (Gr 6), and Omeprazole+PGC-HBEGF+PGC-gastrin (Gr 7) treated animals have significantly lower non-FBG at day 31 than vehicle control (Gr 2). However, only Gr 7 (those that received the induction of endogenous gastrin, exogenous gastrin, plus PGC-HBEGF) have significantly lower glucose area under the curve during the treatment period, indicating that additional gastrin lowers blood sugar during the treatment but may have contributed to higher FBG after the treatment. In addition, early time points prior to the full effect of the treatment diluted the non-FBG glucose area under the curve (gAUC) results as seen by comparison with the non-FBG at day 31.
Gr 5 and Gr 7 have significantly less increase in HbA1c compared to Gr 2 control during the treatment period. Gr 6 and literature positive control Gr 8 did not show any decrease in HbA1c formation compared to vehicle control Gr 2 during the treatment, which may be due to a hyperglycemic effect of the formulations, despite improvement of islet function after the treatment as seen from IPGTT.
Note that Omeprazole alone (Gr 5) or Omeprazole+PGC-HBEGF+PGC-gastrin (Gr 7) showed reduced non-fasting blood glucose during treatment, indicating that gastrin can partially overcome the hyperglycemic effect of HBEGF.