Thiazolidinediones improve insulin sensitivity in adipose tissue and reduce the hyperlipidaemia without affecting the hyperglycaemia in a transgenic model of type 2 diabetes

H. Kim, M. Haluzik, O. Gavrilova, Shoshana Yakar, J. Portas, H. Sun, U. B. Pajvani, P. E. Scherer, D. LeRoith

Research output: Contribution to journalArticle

Abstract

Aim/hypothesis. The aim of this study was to examine the effects of thiazolidinediones on the MKR mouse model of type 2 diabetes. Methods. Six-week-old wild-type (WT) and MKR mice were fed with or without rosiglitazone or pioglitazone for 3 weeks. Blood was collected from the tail vein for serum biochemistry analysis. Hyperinsulinaemic-euglycaemic clamp analysis was performed to study effects of thiazolidinediones on insulin sensitivity of tissues in MKR mice. Northern blot analysis was performed to measure levels of target genes of PPAR γ agonists in white adipose tissue and hepatic gluconeogenic genes. Results. Thiazolidinedione treatment of MKR mice significantly lowered serum lipid levels and increased serum adiponectin levels but did not affect levels of blood glucose and serum insulin. Hyperinsulinaemic-euglycaemic clamp showed that whole-body insulin sensitivity and glucose homeostasis failed to improve in MKR mice after rosiglitazone treatment. Insulin suppression of hepatic endogenous glucose production failed to improve in MKR mice following rosiglitazone treatment. This lack of change in hepatic insulin insensitivity was associated with no change in the ratio of HMW : total adiponectin, hepatic triglyceride content, and sustained hepatic expression of PPAR γ and stearoyl-CoA desaturase 1 mRNA. Interestingly, rosiglitazone markedly enhanced glucose uptake by white adipose tissue with a parallel increase in CD36, aP2 and GLUT4 gene expression. Conclusions/ interpretation. These data suggest that potentiation of insulin action on tissues other than adipose tissue is required to mediate the antidiabetic effects of thiazolidinediones in our MKR diabetic mice.

Original languageEnglish (US)
Pages (from-to)2215-2225
Number of pages11
JournalDiabetologia
Volume47
Issue number12
DOIs
StatePublished - Dec 2004

Fingerprint

rosiglitazone
Thiazolidinediones
Hyperlipidemias
Hyperglycemia
Type 2 Diabetes Mellitus
Insulin Resistance
Adipose Tissue
Liver
Insulin
White Adipose Tissue
Peroxisome Proliferator-Activated Receptors
Glucose Clamp Technique
pioglitazone
Adiponectin
Serum
Glucose
Stearoyl-CoA Desaturase
Hypoglycemic Agents
Northern Blotting
Biochemistry

Keywords

  • Adiponectin
  • Adipose tissue
  • Hyperinsulinaemic-euglycaemic clamp
  • Insulin sensitivity
  • Muscle insulin action
  • Thiazolidinediones

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Thiazolidinediones improve insulin sensitivity in adipose tissue and reduce the hyperlipidaemia without affecting the hyperglycaemia in a transgenic model of type 2 diabetes. / Kim, H.; Haluzik, M.; Gavrilova, O.; Yakar, Shoshana; Portas, J.; Sun, H.; Pajvani, U. B.; Scherer, P. E.; LeRoith, D.

In: Diabetologia, Vol. 47, No. 12, 12.2004, p. 2215-2225.

Research output: Contribution to journalArticle

Kim, H. ; Haluzik, M. ; Gavrilova, O. ; Yakar, Shoshana ; Portas, J. ; Sun, H. ; Pajvani, U. B. ; Scherer, P. E. ; LeRoith, D. / Thiazolidinediones improve insulin sensitivity in adipose tissue and reduce the hyperlipidaemia without affecting the hyperglycaemia in a transgenic model of type 2 diabetes. In: Diabetologia. 2004 ; Vol. 47, No. 12. pp. 2215-2225.
@article{fb4c4941f4124a388029a004fe534c7e,
title = "Thiazolidinediones improve insulin sensitivity in adipose tissue and reduce the hyperlipidaemia without affecting the hyperglycaemia in a transgenic model of type 2 diabetes",
abstract = "Aim/hypothesis. The aim of this study was to examine the effects of thiazolidinediones on the MKR mouse model of type 2 diabetes. Methods. Six-week-old wild-type (WT) and MKR mice were fed with or without rosiglitazone or pioglitazone for 3 weeks. Blood was collected from the tail vein for serum biochemistry analysis. Hyperinsulinaemic-euglycaemic clamp analysis was performed to study effects of thiazolidinediones on insulin sensitivity of tissues in MKR mice. Northern blot analysis was performed to measure levels of target genes of PPAR γ agonists in white adipose tissue and hepatic gluconeogenic genes. Results. Thiazolidinedione treatment of MKR mice significantly lowered serum lipid levels and increased serum adiponectin levels but did not affect levels of blood glucose and serum insulin. Hyperinsulinaemic-euglycaemic clamp showed that whole-body insulin sensitivity and glucose homeostasis failed to improve in MKR mice after rosiglitazone treatment. Insulin suppression of hepatic endogenous glucose production failed to improve in MKR mice following rosiglitazone treatment. This lack of change in hepatic insulin insensitivity was associated with no change in the ratio of HMW : total adiponectin, hepatic triglyceride content, and sustained hepatic expression of PPAR γ and stearoyl-CoA desaturase 1 mRNA. Interestingly, rosiglitazone markedly enhanced glucose uptake by white adipose tissue with a parallel increase in CD36, aP2 and GLUT4 gene expression. Conclusions/ interpretation. These data suggest that potentiation of insulin action on tissues other than adipose tissue is required to mediate the antidiabetic effects of thiazolidinediones in our MKR diabetic mice.",
keywords = "Adiponectin, Adipose tissue, Hyperinsulinaemic-euglycaemic clamp, Insulin sensitivity, Muscle insulin action, Thiazolidinediones",
author = "H. Kim and M. Haluzik and O. Gavrilova and Shoshana Yakar and J. Portas and H. Sun and Pajvani, {U. B.} and Scherer, {P. E.} and D. LeRoith",
year = "2004",
month = "12",
doi = "10.1007/s00125-004-1581-6",
language = "English (US)",
volume = "47",
pages = "2215--2225",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "12",

}

TY - JOUR

T1 - Thiazolidinediones improve insulin sensitivity in adipose tissue and reduce the hyperlipidaemia without affecting the hyperglycaemia in a transgenic model of type 2 diabetes

AU - Kim, H.

AU - Haluzik, M.

AU - Gavrilova, O.

AU - Yakar, Shoshana

AU - Portas, J.

AU - Sun, H.

AU - Pajvani, U. B.

AU - Scherer, P. E.

AU - LeRoith, D.

PY - 2004/12

Y1 - 2004/12

N2 - Aim/hypothesis. The aim of this study was to examine the effects of thiazolidinediones on the MKR mouse model of type 2 diabetes. Methods. Six-week-old wild-type (WT) and MKR mice were fed with or without rosiglitazone or pioglitazone for 3 weeks. Blood was collected from the tail vein for serum biochemistry analysis. Hyperinsulinaemic-euglycaemic clamp analysis was performed to study effects of thiazolidinediones on insulin sensitivity of tissues in MKR mice. Northern blot analysis was performed to measure levels of target genes of PPAR γ agonists in white adipose tissue and hepatic gluconeogenic genes. Results. Thiazolidinedione treatment of MKR mice significantly lowered serum lipid levels and increased serum adiponectin levels but did not affect levels of blood glucose and serum insulin. Hyperinsulinaemic-euglycaemic clamp showed that whole-body insulin sensitivity and glucose homeostasis failed to improve in MKR mice after rosiglitazone treatment. Insulin suppression of hepatic endogenous glucose production failed to improve in MKR mice following rosiglitazone treatment. This lack of change in hepatic insulin insensitivity was associated with no change in the ratio of HMW : total adiponectin, hepatic triglyceride content, and sustained hepatic expression of PPAR γ and stearoyl-CoA desaturase 1 mRNA. Interestingly, rosiglitazone markedly enhanced glucose uptake by white adipose tissue with a parallel increase in CD36, aP2 and GLUT4 gene expression. Conclusions/ interpretation. These data suggest that potentiation of insulin action on tissues other than adipose tissue is required to mediate the antidiabetic effects of thiazolidinediones in our MKR diabetic mice.

AB - Aim/hypothesis. The aim of this study was to examine the effects of thiazolidinediones on the MKR mouse model of type 2 diabetes. Methods. Six-week-old wild-type (WT) and MKR mice were fed with or without rosiglitazone or pioglitazone for 3 weeks. Blood was collected from the tail vein for serum biochemistry analysis. Hyperinsulinaemic-euglycaemic clamp analysis was performed to study effects of thiazolidinediones on insulin sensitivity of tissues in MKR mice. Northern blot analysis was performed to measure levels of target genes of PPAR γ agonists in white adipose tissue and hepatic gluconeogenic genes. Results. Thiazolidinedione treatment of MKR mice significantly lowered serum lipid levels and increased serum adiponectin levels but did not affect levels of blood glucose and serum insulin. Hyperinsulinaemic-euglycaemic clamp showed that whole-body insulin sensitivity and glucose homeostasis failed to improve in MKR mice after rosiglitazone treatment. Insulin suppression of hepatic endogenous glucose production failed to improve in MKR mice following rosiglitazone treatment. This lack of change in hepatic insulin insensitivity was associated with no change in the ratio of HMW : total adiponectin, hepatic triglyceride content, and sustained hepatic expression of PPAR γ and stearoyl-CoA desaturase 1 mRNA. Interestingly, rosiglitazone markedly enhanced glucose uptake by white adipose tissue with a parallel increase in CD36, aP2 and GLUT4 gene expression. Conclusions/ interpretation. These data suggest that potentiation of insulin action on tissues other than adipose tissue is required to mediate the antidiabetic effects of thiazolidinediones in our MKR diabetic mice.

KW - Adiponectin

KW - Adipose tissue

KW - Hyperinsulinaemic-euglycaemic clamp

KW - Insulin sensitivity

KW - Muscle insulin action

KW - Thiazolidinediones

UR - http://www.scopus.com/inward/record.url?scp=12944319825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12944319825&partnerID=8YFLogxK

U2 - 10.1007/s00125-004-1581-6

DO - 10.1007/s00125-004-1581-6

M3 - Article

VL - 47

SP - 2215

EP - 2225

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 12

ER -