Journal
DIABETOLOGIA
Volume 49, Issue 1, Pages 149-157Publisher
SPRINGER
DOI: 10.1007/s00125-005-0051-0
Keywords
diet/exercise; glucose; insulin resistance; [H-3]oleate
Categories
Funding
- NCRR NIH HHS [RR-0585] Funding Source: Medline
- NIDDK NIH HHS [DK50456, DK40484] Funding Source: Medline
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000585] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R29DK040484, P30DK050456, R01DK040484, R37DK040484] Funding Source: NIH RePORTER
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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 ([H-3] oleate), glucose kinetics ([6-H-2(2)] glucose) and substrate oxidation ( indirect calorimetry) before and after pioglitazone ( 30 mg/day for similar to 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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