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Significant Hypoglycemic Effect of a
Perorally-delivered Insulin in the Treatment of Streptozocin-induced
Diabetic Rats
Frank K Leung , Jiang Li, Lanqi Huang and Emily Leung
The effectiveness of an oral insulin (Musulin) in streptozocin-treated
diabetic rats was evaluated by a single-dose or multiple-doses
algorithm method,administered perorally. Experimental and control
groups were performed concurrently and matched with comparable
weight(230 gm),age(4-5 months) and initial glucose levels (330
mg/ml). The differences in these parameters were statistically
insignificant between these two groups. Statistical analysis was
performed using SAS 8.0.Experiment 1 (single-dose, 0.4u/gm): Glucose
was sampled from the Jugular vein at time: 0, 15, 30, 60, 120, 180,
300, 360, 420, 480 min. Results of normalized glucose - Control
group (N=4): 100, 106, 114, 105, 102, 89, 86, 75, 77, 55, 57.
Musulin-treated group (N=4): 100, 101, 95, 61, 45, 37, 29, 32, 33,
36. Sustained statistically significant hypoglycemia occurred at 60,
120, 180, 300 min. ( p<0.025, 0.009, 0.004, 0.02 )and glucose was
lowered by 44.8 - 57.4%. Experiment 2 (algorithm method): Glucose
was sampled from the tails at 9 AM and 4 PM daily for 3 weeks. No
insulin was given if the glucose was at or below 150 mg/ml. Musulin
was administered perorally at 0.05 unit for each 1 mg/ml glucose
rose above 150 mg/ml in week 1, the dose was increased to 0.1 unit
in week 2 and then, to 0.2 unit in week 3. Statistical analysis was
performed by SAS 8.0, compound symmetry of within covariance matrix
and repeated measures of ANOVA. Results of glucose levels - Week 1:
AM glucose difference between control (N=8) and Musulin group (N=12)
was 100.63 (S.E. 35.33), P<0.01; PM difference was 123.87 (S.E.
37.4), P<0.004. Week 2: AM difference was 107.63 (S.E. 40.94),
P<0.01 and PM difference was 135.98 ( S.E. 38.92), P<0.0026. In Week
2, 4 control and 9 Musulin survived. 2 Musulin rats died of
hypoglycemia.In Week 3, 2 control and 9 Musulin survived.Conclusion:
1) Musulin is effective in lowering glucose levels, delivered
perorally as a single dose or multiple doses by algorithm method in
diabetic rats.2) Hypoglycemia occurred within 60 min. 3) More
diabetic rats survived when treated with Musulin than control over a
3 weeks period. |
