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Enhanced escape of non-esterified fatty acids from tissue uptake: its role in impaired insulin-induced lowering of total rate of appearance in obesity and Type II diabetes mellitus

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Abstract

Aims/hypothesis. To estimate non-esterified fatty acids kinetics in patients with Type II (non-insulin-dependent) diabetes mellitus and obese subjects in the postabsorptive state and during hyperinsulinaemia using non-equlibrium tracer conditions.¶Methods. We evaluated the effect of hyperinsulinaemia [euglycaemic clamp with insulin infused at 30 mU · kg–1· h–1 (3–4 h) and 150 mU · kg–1· h–1 (3 h)] on non-esterified fatty acid kinetics, traced with [14C]-palmitate using non-equlibrium tracer conditions in non-obese and obese healthy subjects and Type II diabetic patients (10 per group). Michaelis-Menten kinetics were applied for total non-esterified fatty acid disposal, which was assumed to be composed of total arterial plasma non-esterified fatty acid rate of appearance (equalling the rate of disappearance) and tissue uptake of non-esterified fatty acids derived from intravascular triglyceride hydrolysis. A model was developed to calculate the rate of escape of non-esterified fatty acids from tissue uptake and the net rate of tissue lipolysis.¶Results. Total arterial plasma non-esterified fatty acid rate of appearance was lower in non-obese healthy subjects than in the other groups at low insulin infusion (p < 0.05) and in obese Type II diabetic patients at high insulin infusion (p < 0.05). Plasma triglycerides were also lowest in non-obese healthy subjects during hyperinsulinaemia (p < 0.05 from other groups). The rate of escape from tissue uptake decreased during hyperinsulinaemia (p < 0.05 for each group) but remained higher in obese Type II diabetic patients (p < 0.05 from non-obese healthy subjects). In contrast, net rate of tissue lipolysis was not different between the groups at baseline and its decline during hyperinsulinaemia (p < 0.05 for each group) was similar in all groups.¶Conclusion/interpretation. This study challenges the view that the antilipolytic effect of insulin is impaired in Type II diabetes and obesity. We suggest that a high plasma triglyceride concentration causes a higher escape of non-esterified fatty acids from tissue uptake, leading to an impaired suppression of total arterial plasma rate of appearance during a low degree of hyperinsulinaemia in obese subjects and Type II diabetic patients and during a high degree of hyperinsulinaemia in obese Type II diabetic patients. [Diabetologia (2000) 43: 416–426]

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Received: 4 October 1999 and in revised form: 14 December 1999

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Riemens, S., Sluiter, W. & Dullaart, R. Enhanced escape of non-esterified fatty acids from tissue uptake: its role in impaired insulin-induced lowering of total rate of appearance in obesity and Type II diabetes mellitus. Diabetologia 43, 416–426 (2000). https://doi.org/10.1007/s001250051324

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  • Keywords Non-esterified fatty acids, insulin, Type II diabetes mellitus, obesity, lipolysis, triglycerides.