Chronic insulin infusion induces reversible glucose intolerance in lean rats yet ameliorates glucose intolerance in obese rats
| Autor: | Fei Gao, Jason R.B. Dyck, Nancy Smith, Shereen M. Hamza, Peter E. Light, Patrick E. MacDonald, Carrie-Lynn M. Soltys, Miranda M. Sung |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Blood Glucose Male medicine.medical_specialty medicine.medical_treatment Biophysics 030209 endocrinology & metabolism Endogeny Type 2 diabetes Biochemistry Pathogenesis Rats Sprague-Dawley 03 medical and health sciences Insulin infusion 0302 clinical medicine Insulin resistance Thinness Internal medicine Glucose Intolerance medicine Animals Insulin Obesity Muscle Skeletal Molecular Biology biology business.industry Skeletal muscle Glucose Tolerance Test medicine.disease Rats Insulin receptor 030104 developmental biology Endocrinology medicine.anatomical_structure Glucose Diabetes Mellitus Type 2 Liver biology.protein Insulin Resistance business |
| Zdroj: | Biochimica et biophysica acta. General subjects. 1861(2) |
| ISSN: | 0304-4165 |
| Popis: | Background Although insulin resistance (IR) is a key factor in the pathogenesis of type 2 diabetes (T2D), the precise role of insulin in the development of IR remains unclear. Therefore, we investigated whether chronic basal insulin infusion is causative in the development of glucose intolerance. Methods Normoglycemic lean rats surgically instrumented with i.v. catheters were infused with insulin (3 mU/kg/min) or physiological saline for 6 weeks. At infusion-end, plasma insulin levels along with glucose tolerance were assessed. Results Six weeks of insulin infusion induced glucose intolerance and impaired insulin response in healthy rats. Interestingly, the effects of chronic insulin infusion were completely normalized following 24 h withdrawal of exogenous insulin and plasma insulin response to glucose challenge was enhanced, suggesting improved insulin secretory capacity. As a result of this finding, we assessed whether the effects of insulin therapy followed by a washout could ameliorate established glucose intolerance in obese rats. Obese rats were similarly instrumented and infused with insulin or physiological saline for 7 days followed by 24 h washout. Seven day-insulin therapy in obese rats significantly improved glucose tolerance, which was attributed to improved insulin secretory capacity and improved insulin signaling in liver and skeletal muscle. Conclusion Moderate infusion of insulin alone is sufficient to cause glucose intolerance and impair endogenous insulin secretory capacity, whereas short-term, intensive insulin therapy followed by insulin removal effectively improves glucose tolerance, insulin response and peripheral insulin sensitivity in obese rats. General significance New insight into the link between insulin and glucose intolerance may optimize T2D management. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect