Study on the pharmacodynamics of different administration methods of insulin on type II diabetes model

Abstract

Abstract: AIM:To observe the effects of subcutaneous and intraperitoneal injection for insulin on the rats with Type II diabetes. METHODS: Kk mice with fasting blood sugar level higher than 20 mmol/L was set as Type II diabetes model and divided into subcutaneous injection group (s. c. group, n =6) and intraperitoneal injection group (i. p. group, n =6) with different dosis of insulin, and the tail blood sugar levels were monitored for two continuous hours after administration. RESULTS:Under non-fasting condition, the blood sugar levels of s. c. group and i. p. group were (32. 0 ±1. 5), (31. 0 ±1. 5) mmol/L, respectively before insulin injection, and were decreased gradually after injecting. When insulin dose was not sufficient, the blood sugar level was at the bottom at the 30th minutes, and then went upwards gradually. When the dose was appropriate, the blood sugar level was at normal level at the 30th minutes, and then went upwards gradually after maintaining a certain time. When insulin was overdose, the blood sugar level was below normal level and decreased gradually and slowly. The dose-response curve was drawn according to the blood sugar level at the point of 30 minutes. When the insulin dose was in the range of 1. 1-1. 7 U/kg, the blood sugar level could be stably controlled within normal scope(5. 1 ± 0. 2) mmol/L in i. p. group, and the dose-response curve showed an obvious plateau phase. The dose-response curve showed a linear relation with the blood sugar level in the range of 2. 1-9. 2 mmol/L in s. c. group. The effective dose scope of insulin intraperitoneal injection was ±21% of the subcutaneous injection dose. CONCLUSION:Compared with subcutaneous injection, ntraperitoneal injection can control blood sugar level more stably, cause less fluctuation and a lower chance of hypoglycemia.

Key words: diabetes, insulin, pharmacodynamics

CLC Number:

R965. 2

DENG Shan-shan, ZHANG Chao, TANG Li-na, XIANG Li, SUN Hong-fan. Study on the pharmacodynamics of different administration methods of insulin on type II diabetes model[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(5): 524-527.

References

[1] Henderson JN, Allen KV, Deary IJ, et al. Hypoglycaemia in insulin-treated type 2 diabetes:frequency, symptoms and impaired awareness[J]. Diabet Med, 2003, 20(12): 1016-1021.
[2] Fatourechi MM, Kudva YC, Murad MH, et al.Hypoglycemia with intensive insulin therapy: a systematic review and meta-analyses of randomized trials of continuous subcutaneous insulin infusion versus multiple daily injections [J]. J Clin EndocrinolMetab, 2009, 94(3): 729-740.
[3] Jeandidier N, Selam JL, Renard E, et al.Decreased severe hypoglycemia frequency during intraperitoneal insulin infusion using programmable implantable pumps[J]. Diabetes Care, 1996, 19(7): 780.
[4] 张超, 胡亚楠, 唐丽娜, 等.胰岛素不同给药途径对糖尿病小鼠葡萄糖代谢的影响[J]. 中国临床药理学与治疗学, 2007, 12(8): 927-930.
[5] Grefberg N, Danielson BG, Berne C. Decreasing insulin requirements in CAPD patients given intraperitoneal insulin [J]. J Diabet Complications, 1987, 1(1): 16-19.
[6] Waxman K, Soliman MH, Nguyen KH. Absorption of insulin in the peritoneal cavity in a diabetic animal model [J]. Artif Organs, 1993, 17(11): 925-928.
[7] DuckworthWC, Saudek CD, Henry RR.Why intraperitoneal delivery of insulin with implantable pumps in NIDDM [J] Diabetes, 1992, 41(6): 657-661.
[8] Gupta N, Park E, Sandhu H, et al.Direct and indirect effects of insulin on hepatic glucose production in diabetic depancreatized dogs during eugly cemia[J]. J Endocrinol, 2006, 190(3): 695-702.
[9] Mason TM, Gupta N, Goh T, et al.Chronic intraperitoneal insulin delivery, as compared with subcutaneous delivery, improves hepatic glucose metabolism in streptozotocin diabetic rats[J]. Metabolism, 2000, 49(11): 1411- 1416.
[10] 刘道平, 汪寅间.2 型糖尿病患者血清GH, IGF-Ⅰ 浓度改变及相关性因素的研究[J]. 中国糖尿病杂志,2000, 8(2): 81-84.
[11] Russell-Jones DL, Rattray M, Wilson VJ, et al.Intraperitoneal insulin is more potent than subcutaneous insulin at restoring hepatic insulin-like growth factor-Ⅰ mRNA levels in the diabetic rat:a functional role for the portal vascular link[J]. J Mol Endocrinol, 1992, 9(3): 257-263.
[12] Hanaire-Broutin H, Sallerin-Caute B, Poncet MF, et al. Effect of intraperitoneal insulin delivery on growth hormone binding protein, insulin-like growth factor (IGF)-I, and IGF-binding protein-3 in IDDM[J]. Diabetologia, 1996, 39(12): 1498-1504.
[13] 龚德华.胰岛素样生长因子在糖尿病治疗中的应用[J]. 肾脏病与透析肾移植杂志, 1998, 7(4): 348- 350.
[14] Wan CK, Giacca A, Matsuhisa M, et al.Increased responses of glucagon and glucose production to hypoglycemia with intraperitoneal versus subcutaneous insulin treatment[J]. Metabolism, 2000, 49(8): 984-989.
[15] Oskarsson PR, Lins PE, Backman L, et al. Continuous intraperitoneal insulin infusion partly restores the glucagons response to hypoglycaemia in type 1 diabetic patients[J]. Diabetes Metab, 2000, 26(2): 118-124.
[16] Quellhorst E.Insulin therapy during peritoneal dialysis: pros and cons of various forms of administration[J]. J Am Soc Nephrol, 2002, 13 Suppl 1:S92-S96.
[17] Farina J.Peritoneal dialysis and intraperitoneal insulin: how much[J] ? Nephrol Nurs J, 2004, 31(2): 225-226.
[18] Haardt MJ, Selam JL, Slama G, et al. A cost-benefit comparison of intensive diabetes management with implantable pumps versus multiple subcutaneous injections in patients with type I diabetes[J]. Diabetes Care, 1994, 17 (8): 847-851.