INTRACECALLY ADMINISTERED INSULIN IN CHRONICALLY DIABETIC PIGS

Insulin administered by conventional subcutaneous injection produces s ystemic hyperinsulinemia, which is associated with accelerated atheros clerosis, hyperandrogenism, hyperlipidemia, hypertension, and insulin resistance. This study was undertaken to determine the efficacy of enc apsulated insulin on glycemic control of diabetic pigs over 8 days. Pl asma insulin and serum glucose concentrations were measured in strepto zocin-induced diabetic pigs given enteric peptidase-resistant (methacr ylic acid copolymer encapsulated) insulin. After insulin administratio n, plasma insulin concentrations rose from 5.0 +/- 0.38 U/L to 11.78 /- 1.28 U/L (mean +/- SE). Peak insulin values mere seen between 2.5 a nd 4 hours after capsule administration, raising serum insulin concent rations to between 8.0 and 20.4 U/L. Baseline serum glucose concentrat ions in pigs treated with encapsulated insulin ranged from 175 to 294 mg/dL (mean +/- SE, 226.1 +/- 13.4 mg/dL). Nadir values were seen betw een 3.5 and 5 hours after insulin administration, and nadir serum gluc ose concentrations ranged from 115 to 240 mg/dL (mean +/- SE, 168.2 +/ - 12.8 mg/dL). Diabetic pigs receiving encapsulated insulin for 8 days showed serum glucose concentrations comparable to those achieved with once-daily injections of subcutaneously administered insulin (226.1 /- 13.4 mg/dL vs 249.0 +/- 7.3 mg/dL [mean +/- SE]). None of the diabe tic animals receiving encapsulated insulin developed ketoacidosis or r equired supplemental insulin by injection. Easting serum triglyceride, high-density lipoprotein, and low-density lipoprotein concentrations were comparable in nondiabetic animals and in diabetic animals receivi ng intracecal insulin. Serum cholesterol concentrations mere slightly higher in the diabetic animals (75 +/- 2.5 mg/dL) compared with nondia betic controls (ie, animals prior to induction of diabetes) (61 +/- 1. 7 mg/dL; this difference was significant). Our data indicate that enca psulated insulin can maintain glycemic control in diabetic animals for at least 8 days. However, further studies are needed to determine if orally administered encapsulated insulin can be used to treat patients with diabetes mellitus.