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Oral insulin in diabetic dogs.
1Department of Biochemistry and Molecular Biology, Medical College of Ohio, Toledo 43699-0008.
The Journal of Endocrinology
|November 1, 1991
Summary
Oral insulin delivery in diabetic dogs showed that repeated doses, absorbed from the gastrointestinal tract, effectively lowered plasma glucose and hepatic glucose production, mimicking insulin
Area of Science:
- Pharmacology
- Endocrinology
- Gastroenterology
Background:
- Diabetes mellitus management often relies on injectable insulin.
- Oral insulin delivery presents challenges due to gastrointestinal degradation and absorption barriers.
- Developing effective oral insulin formulations is crucial for improving patient compliance and therapeutic outcomes.
Purpose of the Study:
- To evaluate the efficacy of orally administered bovine crystalline insulin, delivered via azopolymer-coated capsules, in a canine model of diabetes.
- To assess the impact of oral insulin on key metabolic parameters, including plasma glucose, hepatic glucose production, and insulin levels.
- To determine the dose-dependency and duration of action of orally delivered insulin.
Main Methods:
- Bovine crystalline insulin was encapsulated in gelatin capsules and coated with an azopolymer for targeted release in the upper colon.
- Pancreatectomized mongrel dogs with cannulae for portal vein, hepatic vein, and femoral artery access were used.
- Measurements included plasma glucose, insulin, hepatic glucose production rate, hepatic plasma flow, and plasma glucagon-like immunoactivity (GLI) after single and multiple oral insulin doses.
Main Results:
- Single oral doses of insulin in coated capsules led to transient increases in portal plasma insulin and decreases in plasma glucose and hepatic glucose production.
- Multiple oral doses resulted in a dose-dependent reduction in plasma glucose, approaching euglycaemia with higher doses.
- The observed metabolic changes were consistent with insulin acting primarily on the liver, and repeated dosing was necessary for sustained glycemic control.
Conclusions:
- Azopolymer-coated capsules enable oral absorption of bovine crystalline insulin in diabetic dogs.
- Oral insulin absorption effectively modulates hepatic glucose metabolism and reduces hyperglycemia.
- Repeated oral insulin administration is essential for achieving and maintaining normoglycemia in this diabetic model.
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