Role of GH in regulating nocturnal rates of lipolysis and plasma mevalonate levels in normal and diabetic humans

Abstract

To define the role that nocturnal increments in growth hormone (GH) play in maintaining lipolysis, glycerol turnover was measured in six patients with GH deficiency and six normal subjects during sleep. Glycerol production initially decreased in both groups but then increased to 1.44 +/- 0.20 mumol.kg-1.min-1 by 0800 h in normal subjects, whereas GH deficiency was associated with a continuous fall to 0.77 +/- 0.10 mumol.kg-1.min-1, P less than 0.02. Nonesterified fatty acid levels paralleled these changes. Six GH-deficient patients received basal GH replacement including a pulse during sleep, which resulted in normal fasting fatty acid levels (P less than 0.05, replaced vs. chronic deficiency). To assess a possible link between the normal nocturnal increase in plasma mevalonate (the product of the rate-limiting step in cholesterol synthesis) and sleep-associated GH release, 11 GH-deficient patients and 11 normal subjects were studied. Peak nocturnal and fasting mevalonate concentrations were not correlated with GH level. We conclude that nocturnal growth hormone secretion is essential for maintaining lipolysis but that it is not related to normal increments in mevalonate and, by inference, to cholesterol synthesis during sleep.

A circadian rhythm in lipid mobilization which is altered in IDDM

“…Thus, increased rates of nocturnal lipolysis and blood flow in subcutaneous adipose tissue could together be responsible for elevated concentrations at NEFA at night. A constant rate of glycerol turnover in vivo during the night has been demonstrated in healthy subjects [9,10]. Methodological factors may explain the divergence in results.…”

The Effects of Insulin on Plasma Mevalonate Concentrations in Man

“…One possibility is that the decrease in long-chain fatty acids arriving at the liver had decreased acetyl CoA for mevalonate synthesis [22]. However, a recent paper which aimed to eval uate the role of growth hormone in regulating nocturnal lipolysis failed to demonstrate a relationship between plasma free fatty acids and a normal increment in mevalonate con centrations [23]. Another possible explana tion resides on the insulin ability to stimulate LDL receptor activity.…”

Diminished brain glucose metabolism is a significant determinant for falling rates of systemic glucose utilization during sleep in normal humans.

“…These alterations include such diverse events as decrements in central nervous system electrical activity (1), reduced basal metabolic rate (2), decreased cardiac output (3), as well as concomitant reductions in rates of systemic glucose turnover in normal (4) and diabetic humans (5). In direct response to sleep, adrenocorticotrophin (6), and growth hormone (7) are released from the anterior pituitary and exert major influences on systemic glucose metabolism during the ensuing hours (8)(9)(10). Two recent reviews consolidate the fragments of our present knowl-edge ofthe metabolism of sleep (11,12), yet substantial details regarding interrelationships between brain and whole body fuel kinetics are incomplete.…”