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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Intensive insulin treatment induces insulin resistance in diabetic rats by impairing glucose metabolism-related mechanisms in muscle and liver

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Author(s):
Okamoto, Maristela Mitiko [1] ; Anhe, Gabriel Forato [2] ; Sabino-Silva, Robinson [1] ; dos Santos Ferreira Marques, Milano Felipe [1] ; Freitas, Helayne Soares [1] ; Tieko Mori, Rosana Cristina [1] ; Melo, Karla Fabiana S. [3] ; Machado, Ubiratan Fabres [1]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05505900 Sao Paulo - Brazil
[2] Univ Estadual Campinas, Fac Med Sci, Dept Pharmacol, Sao Paulo - Brazil
[3] Univ Sao Paulo, Sch Med, Div Endocrinol & Metab, Diabet Unit, BR-05505900 Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Journal of Endocrinology; v. 211, n. 1, p. 55-64, OCT 2011.
Web of Science Citations: 37
Abstract

Insulin replacement is the only effective therapy to manage hyperglycemia in type 1 diabetes mellitus (T1DM). Nevertheless, intensive insulin therapy has inadvertently led to insulin resistance. This study investigates mechanisms involved in the insulin resistance induced by hyperinsulinization. Wistar rats were rendered diabetic by alloxan injection, and 2 weeks later received saline or different doses of neutral protamine Hagedorn insulin (1.5, 3, 6, and 9 U/day) over 7 days. Insulinopenic-untreated rats and 6U- and 9U-treated rats developed insulin resistance, whereas 3U-treated rats revealed the highest grade of insulin sensitivity, but did not achieve good glycemic control as 6U- and 9U-treated rats did. This insulin sensitivity profile was in agreement with glucose transporter 4 expression and translocation in skeletal muscle, and insulin signaling, phosphoenolpyruvate carboxykinase/glucose-6-phosphatase expression and glycogen storage in the liver. Under the expectation that insulin resistance develops in hyperinsulinized diabetic patients, we believe insulin sensitizer approaches should be considered in treating T1DM. Journal of Endocrinology (2011) 211, 55-64 (AU)