Abstract
The purpose of this study was to investigate the involvement of growth hormone in the diurnal variation of insulin sensitivity in healthy adults. Afternoon (16:00 hr) or night (23:00 hr) pretreatment with a subcutaneous injection of normal saline, human growth hormone to mimic the normal nocturnal rise in growth hormone, or octreotide to inhibit endogenous growth hormone secretion to create a state of relative nocturnal growth hormone deficiency, was given 16 hours before undergoing the modified insulin suppression test in healthy subjects. The morning and evening experiments were separated by an interval of at least 3 days. Thus, each subject was tested on six separate occasions arranged in a random order. A higher value of the steady-state plasma glucose (SSPG) is indicative of lower insulin sensitivity. Plasma glucose, serum insulin, insulin-like growth factor-1, nonesterified fatty acids (NEFA), and metabolic clearance rate of insulin (MCRI) were measured. In the normal saline and human growth hormone groups, SSPG levels were lower in the morning than in the evening. Evening SSPG levels, MCRI, and NEFA concentrations were higher in the participants treated with normal saline and growth hormone than in the octreotide group. Differences in SSPG levels between the morning and evening values were higher in the participants pretreated with normal saline and growth hormone than in those treated with octreotide. A diurnal variation in insulin sensitivity existed in healthy subjects. These results provided direct evidence that the role of growth hormone in regulating insulin sensitivity might be related to changes in the MCRI and the metabolism of NEFA in healthy subjects.
Highlights
A diurnal variation in glucose tolerance and insulin sensitivity to a glucose load has been reported in human subjects [1]
The results showed that a surge of growth hormone induced a reduction in insulin sensitivity in the healthy subjects
Administration of human growth hormone revealed that the steady-state plasma glucose (SSPG) levels were lower in the morning than in the evening, providing evidence of the diurnal variation in insulin sensitivity
Summary
A diurnal variation in glucose tolerance and insulin sensitivity to a glucose load has been reported in human subjects [1]. The relatively impaired glucose tolerance observed in the afternoon or the evening is associated with a delayed insulin response to the glucose load, which is probably due to a decreased sensitivity of pancreatic β cells to glucose [3] This “dawn phenomenon” was first described in the 1980s as abrupt increases in fasting levels of plasma glucose, insulin requirement, or both in the early morning between 05:00 and 09:00 hr without antecedent to hypoglycemia. Time of day was found to influence glucose regulation in healthy subjects [10] Together, these findings suggest that the diurnal variation in insulin sensitivity may be related to a growth hormone-induced increase in insulin secretion in the early morning for the maintenance of normoglycemia [6] [8] [9]. Growth hormone concentrations are known to vary considerably throughout the day in healthy subjects [4] [11]-[13]; the physiological role of growth hormone-induced diurnal variation in glucose tolerance and insulin sensitivity remains unclear
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