Mechanism of regulation of glucose production by lipolysis in humans

The relationship between the rate of lipolysis and rate of glucose production (R(a)) was investigated in 14- and 86-h fasted humans. [6,6- ²H]glucose and [²H]₅ glycerol were infused to measure glucose and glycerol R(a) in response to infusions of nicotinic acid in 14- and 86-h fasted subjects (protocol 1). The response of glucose R(a) to nicotinic acid alone and nicotinic acid plus unlabeled glycerol was also measured in 86-h fasted subjects (protocol 2). After a 14-h fast, nicotinic acid caused a 30% decrease in plasma insulin levels and a marked (66%) decrease in plasma free fatty acid levels but did not have any significant effect on glucose R(a) and concentration. After 86 h of fasting, nicotinic acid decreased glycerol R(a) and hence lipolytic rate by ~60%. This caused a significant decrease (P < 0.05) of 16-20% in glucose R(a) and uptake. This decrease in glucose R(a) was abolished when unlabeled glycerol was also infused with nicotinic acid to maintain glycerol R(a). These findings suggest that, in normal humans, a decrease in the rate of lipolysis regulates glucose R(a) via its effect on the availability of glycerol for gluconeogenesis.