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.
OBJECTIVE
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-equilibrium tracer conditions.


METHODS
We evaluated the effect of hyperinsulinaemia [euglycaemic clamp with insulin infused at 30 mU x kg(-1) x h(-1) (3-4 h) and 150 mU x kg(-1) x h(-1) (3 h)] on non-esterified fatty acid kinetics, traced with [14C]-palmitate using non-equilibrium 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.


CONCLUSIONS
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.
Riemens
S C
SC
Department of Endocrinology, University Hospital Groningen, The Netherlands.
Sluiter
W J
WJ
Dullaart
R P
RP
D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D005230:Fatty Acids, Nonesterified / Q000097:blood* / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D006868:Hydrolysis; D007328:Insulin / Q000008:administration & dosage / Q000097:blood*; D007700:Kinetics; D008657:Metabolic Clearance Rate; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D013453:Sulfonylurea Compounds; D014280:Triglycerides; D008687:Metformin