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

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 2004

Fingerprint

Phlorhizin
Hyperglycemia
Type 2 Diabetes Mellitus
Transgenic Mice
Insulin Resistance
Liver
Glucose
Insulin
Blood Glucose
White Adipose Tissue
IGF Type 1 Receptor
Glucose Clamp Technique
Hyperinsulinism
Dyslipidemias
Skeletal Muscle
Triglycerides
Fatty Acids
Eating
Fats
Urine

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Phloridzin improves hyperglycemia but not hepatic insulin resistance in a transgenic mouse model of type 2 diabetes. / Zhao, Hong; Yakar, Shoshana; Gavrilova, Oksana; Sun, Hui; Zhang, Yang; Kim, Hyunsook; Setser, Jennifer; Jou, William; LeRoith, Derek.

In: Diabetes, Vol. 53, No. 11, 11.2004, p. 2901-2909.

Research output: Contribution to journalArticle

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, vol. 53, no. 11, pp. 2901-2909. https://doi.org/10.2337/diabetes.53.11.2901
Zhao, Hong ; Yakar, Shoshana ; Gavrilova, Oksana ; Sun, Hui ; Zhang, Yang ; Kim, Hyunsook ; Setser, Jennifer ; Jou, William ; LeRoith, Derek. / Phloridzin improves hyperglycemia but not hepatic insulin resistance in a transgenic mouse model of type 2 diabetes. In: Diabetes. 2004 ; Vol. 53, No. 11. pp. 2901-2909.
@article{dcc4763cc44d49a6b2bfe7d4a111549d,
title = "Phloridzin improves hyperglycemia but not hepatic insulin resistance in a transgenic mouse model of type 2 diabetes",
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.",
author = "Hong Zhao and Shoshana Yakar and Oksana Gavrilova and Hui Sun and Yang Zhang and Hyunsook Kim and Jennifer Setser and William Jou and Derek LeRoith",
year = "2004",
month = "11",
doi = "10.2337/diabetes.53.11.2901",
language = "English (US)",
volume = "53",
pages = "2901--2909",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "11",

}

TY - JOUR

T1 - Phloridzin improves hyperglycemia but not hepatic insulin resistance in a transgenic mouse model of type 2 diabetes

AU - Zhao, Hong

AU - Yakar, Shoshana

AU - Gavrilova, Oksana

AU - Sun, Hui

AU - Zhang, Yang

AU - Kim, Hyunsook

AU - Setser, Jennifer

AU - Jou, William

AU - LeRoith, Derek

PY - 2004/11

Y1 - 2004/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=7044247671&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7044247671&partnerID=8YFLogxK

U2 - 10.2337/diabetes.53.11.2901

DO - 10.2337/diabetes.53.11.2901

M3 - Article

VL - 53

SP - 2901

EP - 2909

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 11

ER -