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Regulation of the growth hormone-independent growth factor-binding protein in children
A M Cotterill1, C T Cowell, R C Baxter
1Ray Williams Institute of Endocrinology, Royal Alexandra Hospital for Children, Camperdown, New South Wales, Australia.
Insights
The diurnal variation of growth hormone-independent insulin-like growth factor-binding protein (BP-28) in children is regulated by metabolic status, not an intrinsic rhythm. Metabolic changes like feeding or fasting significantly alter BP-28 levels throughout the day.
Area of Science:
- Pediatric Endocrinology
- Metabolic Regulation
- Hormone Dynamics
Background:
- The diurnal variation of growth hormone-independent insulin-like growth factor-binding protein (BP-28) is not well understood.
- Previous studies have not clarified whether BP-28's daily fluctuations are due to an internal biological clock or external metabolic factors.
- Understanding BP-28 regulation is crucial for interpreting its role in pediatric endocrine health.
Purpose of the Study:
- To investigate the regulatory mechanisms behind the diurnal variation of plasma BP-28 concentrations in children.
- To determine if metabolic status, such as feeding, fasting, or glucose/insulin challenges, influences BP-28 levels.
- To differentiate between an intrinsic rhythm and metabolic regulation of BP-28 diurnal patterns.
Main Methods:
- Studied 53 children undergoing endocrine investigations.
- Measured plasma BP-28 levels at various time points over 24 hours.
- Administered interventions including a light meal, water, oral glucose, and insulin-induced hypoglycemia to assess metabolic influence.
Main Results:
- Plasma BP-28 levels exhibited a 12-fold increase from evening to early morning, inversely related to insulin but not cortisol.
- A light meal significantly altered the overnight rise, causing a temporary fall and subsequent rise in BP-28.
- Oral glucose administration rapidly decreased morning BP-28 levels, while fasting led to a continued increase; insulin-induced hypoglycemia caused a sharp rise.
Conclusions:
- The diurnal variation of plasma BP-28 in children is primarily regulated by the child's metabolic state.
- Feeding, fasting, and glucose/insulin dynamics significantly impact BP-28 concentrations, suggesting it is a responsive metabolic marker.
- BP-28 diurnal variation is not driven by an intrinsic circadian rhythm but by the body's response to metabolic cues.
Abstract:
Regulation of the diurnal variation of the GH-independent insulin-like growth factor-binding protein (BP-28) was studied in 53 children who underwent various investigations for possible endocrine abnormalities. The plasma BP-28 levels increased 12-fold from 8 +/- 2 (+/-SE) micrograms/L at 2100 h to a peak level of 109 +/- 15 micrograms/L between 0600 and 0800 h. This rise was inversely related to plasma insulin levels and was unrelated to plasma cortisol levels. The overnight rise of plasma BP-28 was significantly altered in children who ate a light meal at 0130 h; in them BP-28 levels started to fall after 0300 h, reached nadir levels at 0400 h, began to rise again by 0700 h, and returned to control levels by 0800 h. Such changes did not occur in children given water alone. From the peak early morning level, plasma BP-28 fell to basal levels in children given oral glucose at 0800 h; the t1/2 of the fall was 55 +/- 9 (+/-SE) min. In children who continued to fast, plasma BP-28 did not fall but, rather, increased from 144 +/- 12 micrograms/L at 0800 h after 10 h of fasting to 239 +/- 30 micrograms/L by 1600 h. The induction of hypoglycemia by insulin given at 0945 h after an overnight fast caused a similar but more rapid rise in plasma BP-28 to 668 +/- 317 micrograms/L (range, 208-1763 micrograms/L) by 1230 h. These results suggest that the diurnal variation of plasma BP-28 concentrations in children is not due to an intrinsic rhythm, but is regulated by the metabolic status of the child.