Artificial induction of intravascular lipolysis by lipid-heparin infusion leads to insulin resistance in man

Abstract

Although extensive evidence indicates that free fatty acids can decrease glucose utilization in vitro, it is still controversial how an increase in lipolysis affects glucose metabolism in man. To test the hypothesis that an increase in lipolysis is related to insulin resistance, we examined the effect of lipid-heparin infusion on glucose metabolism in ten normal subjects by the euglycaemic glucose clamp technique and isotopic determination of glucose turnover. In the control euglycaemic clamp studies with insulin infusion at 0.2 and 1.0mU.kg-l.min -1, endogenous glucose production was suppressed from the basal rate of 2.0+_0.3 mg. kg-lmin -1 to 1.1 _+0.7 mg.kg -1.min -I and -0.4+_0.7 mg. kg-lmin -1 respectively. Glucose utilization increased from the basal rate of 2.0+_0.3 mg.kg-lmin -1 to 2.3+_0.5 mg. kg-lmin -1 and 5.9+1.8 mg.kg-lmin -1 respectively. When the euglycaemic clamp studies were coupled with lipid-heparin infusion at comparable low and high rates of insulin infusion, endogenous glucose production increased (1.8+ 0.7 mg.kg -1.rain -1, p<0.001, and 0.3 +_0.6mg.kg -1. min -1, p<0.05, respectively), and glucose utilization decreased (2.1+_0.3mg.kg-l.min -1, not significant, and 3.2 +_ 0.7 rag. kg-1. rain-i, p< 0.001 respectively). These data suggest that the artificial induction of intravascular lipolysis by lipid-heparin infusion leads to a state of insulin resistance in man.

Free fatty acids FFA a link between obesity and insulin resistance

“…Other studies showed that the lipid induced inhibition of insulin stimulated glucose uptake was linear (14,15) "figure 3" and occurred similarly in healthy subjects and in patients with Type II diabetes (14)(15)(16)(17)(18)(19)(20). The long delay of 3-4 hours between the start of the insulin and lipid infusions and the development of significant insulin resistance was the most likely reason why the inhibitory effect of FFA on glucose uptake was not found in many previous studies (21)(22)(23)(24)(25).…”