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Exogenous hyperinsulinemia causes insulin resistance, hyperendothelinemia, and subsequent hypertension in rats
- Source :
- Metabolism. 48:465-471
- Publication Year :
- 1999
- Publisher :
- Elsevier BV, 1999.
-
Abstract
- In many clinical and animal studies, hypertension and insulin resistance coexist, but their mechanistic relationship is unclear. We explored the causal link between these two parameters in a rat model with chronic hyperinsulinemia induced with human insulin (1 U/d) released from subcutaneously implanted minipumps. Rats with saline minipumps served as a control. During the first experiment, plasma levels of insulin and glucose and the systolic blood pressure of the two groups were continuously monitored for 17 days. In the subsequent four experiments, rats were killed on days 10 and 13 to measure plasma endothelin-1 (ET-1) levels and the glucose transport into and insulin and ET-1 binding of isolated adipocytes. In one experiment, rats were tested for oral glucose tolerance on days 10 and 13. In another experiment, ET-1 binding to the aortic plasma membrane was also determined. The results showed that rats became hyperinsulinemic throughout the experimental period by the instillation of exogenous insulin. Hyperinsulinemic rats were consistently hypoglycemic during the first day, but they became euglycemic thereafter, indicating an insulin-resistant state. Glucose intolerance was obvious by day 10, but significant hypertension was not detected until the 11th day on insulin infusion. Compared with the saline controls, insulin-infused rats had an increase of plasma ET-1 levels but a decrease of both basal and insulin-stimulated glucose transport into adipocytes. ET-1 binding to adipocytes of the insulin-infused group was elevated significantly from day 10 through day 13. ET-1 binding to the aortic membranes, supposedly downregulated by the increased plasma ET-1 and hypertension, was similar to that found in the controls on day 13. These results imply that hyperinsulinemia in rats could lead to hypertension via the elevation of plasma ET-1 levels together with an unaltered vascular binding of ET-1, which was probably unrelated to the insulin resistance.
- Subjects :
- Blood Glucose
Male
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Blood Pressure
Rats, Sprague-Dawley
Insulin Infusion Systems
Endocrinology
Insulin resistance
Hyperinsulinism
Internal medicine
Blood plasma
Adipocytes
medicine
Hyperinsulinemia
Animals
Hypoglycemic Agents
Insulin
Pancreatic hormone
Endothelin-1
business.industry
Cell Membrane
Glucose transporter
Glucose Tolerance Test
medicine.disease
Rats
Blood pressure
Basal (medicine)
Hypertension
Endothelium, Vascular
Insulin Resistance
business
Subjects
Details
- ISSN :
- 00260495
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- Metabolism
- Accession number :
- edsair.doi.dedup.....42201c79777fb6236eaed9e38acfc82f