Phloridzin improves hyperglycemia but not hepatic insulin resistance in a transgenic mouse model of type 2 diabetes

Hong Zhao, Shoshana Yakar, Oksana Gavrilova, Hui Sun, Yang Zhang, Hyunsook Kim, Jennifer Setser, William Jou, Derek LeRoith

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

The chronic hyperglycemia that occurs in type 2 diabetes may cause deterioration of β-cell function and insulin resistance in peripheral tissues. Mice that express a dominant-negative IGF-1 receptor, specifically in skeletal muscle (MKR mice), exhibit severe insulin resistance, hyperinsulinemia, dyslipidemia, and hyperglycemia. To determine the role of hyperglycemia in the worsening of the diabetes state in these animals, MKR mice were treated with phloridzin (PHZ), which inhibits intestinal glucose uptake and renal glucose reabsorption. Blood glucose levels were decreased and urine glucose levels were increased in response to PHZ treatment in MKR mice. PHZ treatment also increased food intake in MKR mice; however, the fat mass was decreased and lean body mass did not change. Serum insulin, fatty acid, and triglyceride levels were not affected by PHZ treatment in MKR mice. Hyperinsulinemic-euglycemic clamp analysis demonstrated that glucose uptake in white adipose tissue was significantly increased in response to PHZ treatment. Despite the reduction in blood glucose following PHZ treatment, there was no improvement in insulin-stimulated whole-body glucose uptake in MKR mice and neither was there suppression of endogenous glucose production by insulin. These results suggest that glucotoxicity plays little or no role in the worsening of insulin resistance that occurs in the MKR mouse model of type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)2901-2909
Number of pages9
JournalDiabetes
Volume53
Issue number11
DOIs
StatePublished - Nov 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Zhao, H., Yakar, S., Gavrilova, O., Sun, H., Zhang, Y., Kim, H., Setser, J., Jou, W., & LeRoith, D. (2004). Phloridzin improves hyperglycemia but not hepatic insulin resistance in a transgenic mouse model of type 2 diabetes. Diabetes, 53(11), 2901-2909. https://doi.org/10.2337/diabetes.53.11.2901