Effects of pioglitazone and metformin on NEFA-induced insulin resistance in type 2 diabetes

R. Basu, A. Basu, V. Chandramouli, B. Norby, B. Dicke, P. Shah, O. Cohen, B. R. Landau, R. A. Rizza

Research output: Contribution to journalArticle

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Abstract

Aims/hypothesis: We sought to determine whether pioglitazone and metformin alter NEFA-induced insulin resistance in type 2 diabetes and, if so, the mechanism whereby this is effected. Methods: Euglycaemic-hyperinsulinaemic clamps (glucose ∼5.3 mmol/l, insulin ∼200 pmol/l) were performed in the presence of Intralipid-heparin (IL/H) or glycerol before and after 4 months of treatment with pioglitazone (n=11) or metformin (n=9) in diabetic participants. Hormone secretion was inhibited with somatostatin in all participants. Results: Pioglitazone increased insulin-stimulated glucose disappearance (p<0.01) and increased insulin-induced suppression of glucose production (p<0.01), gluconeogenesis (p<0.05) and glycogenolysis (p<0.05) during IL/H. However, glucose disappearance remained lower (p<0.05) whereas glucose production (p<0.01), gluconeogenesis (p<0.05) and glycogenolysis (p<0.05) were higher on the IL/H study day than on the glycerol study day, indicating persistence of NEFA-induced insulin resistance. Metformin increased (p<0.001) glucose disappearance during IL/H to rates present during glycerol treatment, indicating protection against NEFA-induced insulin resistance in extrahepatic tissues. However, glucose production and gluconeogenesis (but not glycogenolysis) were higher (p<0.01) during IL/H than during glycerol treatment with metformin, indicating persistence of NEFA-induced hepatic insulin resistance. Conclusions/interpretation: We conclude that pioglitazone improves both the hepatic and the extrahepatic action of insulin but does not prevent NEFA-induced insulin resistance. In contrast, whereas metformin prevents NEFA-induced extrahepatic insulin resistance, it does not protect against NEFA-induced hepatic insulin resistance.

Original languageEnglish (US)
Pages (from-to)2031-2040
Number of pages10
JournalDiabetologia
Volume51
Issue number11
DOIs
StatePublished - Nov 2008

Fingerprint

pioglitazone
Metformin
Nonesterified Fatty Acids
Type 2 Diabetes Mellitus
Insulin Resistance
Glucose
Glycogenolysis
Glycerol
Gluconeogenesis
Heparin
Insulin
Liver
Glucose Clamp Technique
Somatostatin

Keywords

  • Gluconeogenesis
  • Glycogenolysis
  • Insulin resistance
  • Metformin
  • Non-esterified fatty acids
  • Thiazolidinediones
  • Type 2 diabetes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Basu, R., Basu, A., Chandramouli, V., Norby, B., Dicke, B., Shah, P., ... Rizza, R. A. (2008). Effects of pioglitazone and metformin on NEFA-induced insulin resistance in type 2 diabetes. Diabetologia, 51(11), 2031-2040. https://doi.org/10.1007/s00125-008-1138-1

Effects of pioglitazone and metformin on NEFA-induced insulin resistance in type 2 diabetes. / Basu, R.; Basu, A.; Chandramouli, V.; Norby, B.; Dicke, B.; Shah, P.; Cohen, O.; Landau, B. R.; Rizza, R. A.

In: Diabetologia, Vol. 51, No. 11, 11.2008, p. 2031-2040.

Research output: Contribution to journalArticle

Basu, R, Basu, A, Chandramouli, V, Norby, B, Dicke, B, Shah, P, Cohen, O, Landau, BR & Rizza, RA 2008, 'Effects of pioglitazone and metformin on NEFA-induced insulin resistance in type 2 diabetes', Diabetologia, vol. 51, no. 11, pp. 2031-2040. https://doi.org/10.1007/s00125-008-1138-1
Basu, R. ; Basu, A. ; Chandramouli, V. ; Norby, B. ; Dicke, B. ; Shah, P. ; Cohen, O. ; Landau, B. R. ; Rizza, R. A. / Effects of pioglitazone and metformin on NEFA-induced insulin resistance in type 2 diabetes. In: Diabetologia. 2008 ; Vol. 51, No. 11. pp. 2031-2040.
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AU - Basu, A.

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AU - Norby, B.

AU - Dicke, B.

AU - Shah, P.

AU - Cohen, O.

AU - Landau, B. R.

AU - Rizza, R. A.

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N2 - Aims/hypothesis: We sought to determine whether pioglitazone and metformin alter NEFA-induced insulin resistance in type 2 diabetes and, if so, the mechanism whereby this is effected. Methods: Euglycaemic-hyperinsulinaemic clamps (glucose ∼5.3 mmol/l, insulin ∼200 pmol/l) were performed in the presence of Intralipid-heparin (IL/H) or glycerol before and after 4 months of treatment with pioglitazone (n=11) or metformin (n=9) in diabetic participants. Hormone secretion was inhibited with somatostatin in all participants. Results: Pioglitazone increased insulin-stimulated glucose disappearance (p<0.01) and increased insulin-induced suppression of glucose production (p<0.01), gluconeogenesis (p<0.05) and glycogenolysis (p<0.05) during IL/H. However, glucose disappearance remained lower (p<0.05) whereas glucose production (p<0.01), gluconeogenesis (p<0.05) and glycogenolysis (p<0.05) were higher on the IL/H study day than on the glycerol study day, indicating persistence of NEFA-induced insulin resistance. Metformin increased (p<0.001) glucose disappearance during IL/H to rates present during glycerol treatment, indicating protection against NEFA-induced insulin resistance in extrahepatic tissues. However, glucose production and gluconeogenesis (but not glycogenolysis) were higher (p<0.01) during IL/H than during glycerol treatment with metformin, indicating persistence of NEFA-induced hepatic insulin resistance. Conclusions/interpretation: We conclude that pioglitazone improves both the hepatic and the extrahepatic action of insulin but does not prevent NEFA-induced insulin resistance. In contrast, whereas metformin prevents NEFA-induced extrahepatic insulin resistance, it does not protect against NEFA-induced hepatic insulin resistance.

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KW - Non-esterified fatty acids

KW - Thiazolidinediones

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