Mechanism of regulation of glucose production by lipolysis in humans.

The relationship between the rate of lipolysis and rate of glucose production (Ra) was investigated in 14- and 86-h fasted humans. [6,6-2H]glucose and [2H]5glycerol were infused to measure glucose and glycerol Ra in response to infusions of nicotinic acid in 14- and 86-h fasted subjects (protocol 1). The response of glucose Ra 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 Ra and concentration. After 86 h of fasting, nicotinic acid decreased glycerol Ra and hence lipolytic rate by approximately 60%. This caused a significant decrease (P less than 0.05) of 16-20% in glucose Ra and uptake. This decrease in glucose Ra was abolished when unlabeled glycerol was also infused with nicotinic acid to maintain glycerol Ra. These findings suggest that, in normal humans, a decrease in the rate of lipolysis regulates glucose Ra via its effect on the availability of glycerol for gluconeogenesis.