Pioglitazone increases non-esterified fatty acid clearance in upper body obesity

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Aims/hypothesis: Plasma NEFA concentrations are largely determined by adipose tissue lipolysis. Insulin suppression of lipolysis is commonly impaired with insulin resistance and improves with thiazolidinedione treatment of type 2 diabetes. The present studies were designed to assess the effects of thiazolidinedione on NEFA (oleate) metabolism that are independent of improved glycaemic control. Materials and methods: We measured plasma oleate concentration and flux ([3H]oleate), glucose kinetics ([6- 2H2] glucose) and substrate oxidation (indirect calorimetry) before and after pioglitazone (30 mg/day for ∼20 weeks) in 20 non-diabetic adults with upper body obesity. To assess the effects of improved insulin sensitivity per se we performed the same measurements in a matched group of volunteers treated with diet/exercise. Half of the two groups underwent these measurements during a hyperinsulinaemic-euglycaemic clamp, and the other half had their measurements taken during a (control) saline infusion before and after the intervention. Results: Both interventions increased insulin-stimulated glucose disposal and reduced plasma oleate concentrations during the insulin clamp. After diet/exercise, oleate flux decreased (p=0.03) during the insulin clamp and oleate clearance remained unchanged (p=0.55), whereas in the pioglitazone group, oleate flux during the clamp was unchanged (p=0.97) and oleate clearance increased (p=0.003). Oleate clearance in the saline control condition was increased in the pioglitazone group compared with the diet/exercise group (p=0.02). Conclusions/ interpretation: In insulin-resistant, non-diabetic adults, pioglitazone increases NEFA clearance during physiological hyperinsulinaemia, whereas improved insulin sensitivity achieved by diet/exercise does not alter NEFA clearance but enhances insulin suppression of NEFA release. This action of pioglitazone may contribute to improved glucose metabolism in type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)149-157
Number of pages9
JournalDiabetologia
Volume49
Issue number1
DOIs
StatePublished - Jan 2006

Fingerprint

pioglitazone
Oleic Acid
Fatty Acids
Obesity
Nonesterified Fatty Acids
Insulin
Exercise
Diet
Insulin Resistance
Glucose
Lipolysis
Type 2 Diabetes Mellitus
Indirect Calorimetry
Glucose Clamp Technique
Hyperinsulinism

Keywords

  • [H]Oleate
  • Diet/exercise
  • Glucose
  • Insulin resistance

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Pioglitazone increases non-esterified fatty acid clearance in upper body obesity. / Shadid, S.; Jensen, Michael Dennis.

In: Diabetologia, Vol. 49, No. 1, 01.2006, p. 149-157.

Research output: Contribution to journalArticle

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abstract = "Aims/hypothesis: Plasma NEFA concentrations are largely determined by adipose tissue lipolysis. Insulin suppression of lipolysis is commonly impaired with insulin resistance and improves with thiazolidinedione treatment of type 2 diabetes. The present studies were designed to assess the effects of thiazolidinedione on NEFA (oleate) metabolism that are independent of improved glycaemic control. Materials and methods: We measured plasma oleate concentration and flux ([3H]oleate), glucose kinetics ([6- 2H2] glucose) and substrate oxidation (indirect calorimetry) before and after pioglitazone (30 mg/day for ∼20 weeks) in 20 non-diabetic adults with upper body obesity. To assess the effects of improved insulin sensitivity per se we performed the same measurements in a matched group of volunteers treated with diet/exercise. Half of the two groups underwent these measurements during a hyperinsulinaemic-euglycaemic clamp, and the other half had their measurements taken during a (control) saline infusion before and after the intervention. Results: Both interventions increased insulin-stimulated glucose disposal and reduced plasma oleate concentrations during the insulin clamp. After diet/exercise, oleate flux decreased (p=0.03) during the insulin clamp and oleate clearance remained unchanged (p=0.55), whereas in the pioglitazone group, oleate flux during the clamp was unchanged (p=0.97) and oleate clearance increased (p=0.003). Oleate clearance in the saline control condition was increased in the pioglitazone group compared with the diet/exercise group (p=0.02). Conclusions/ interpretation: In insulin-resistant, non-diabetic adults, pioglitazone increases NEFA clearance during physiological hyperinsulinaemia, whereas improved insulin sensitivity achieved by diet/exercise does not alter NEFA clearance but enhances insulin suppression of NEFA release. This action of pioglitazone may contribute to improved glucose metabolism in type 2 diabetes.",
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