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. Author manuscript; available in PMC: 2014 Nov 1.
Published in final edited form as: Pharm Res. 2013 Jun 21;30(11):2843–2854. doi: 10.1007/s11095-013-1112-6

Table II.

Glucose homeostasis parameters showing Glycemia during the treatment, Group (Gr) descriptions are in Table I, n=8

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
a

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.

b

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.