Role of IGF Binding Protein- 1 in the Dawn Phenomenon and Glycemic Control in Children and Adolescents With IDDM

Kobayashi, Koji; Amemiya, Shin; Sawanobori, Emi; Higashida, Kosuke; Ishihara, Tsukasa; Kato, Kiyohiko; Nakazawa, Shinpei

doi:10.2337/diacare.20.9.1442

Cited by 29 publications

(24 citation statements)

References 31 publications

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“…The increase in IGFBP-1 levels may not be merely a consequence of insulin defic i e n c y / r e s i stance but might play a role in the pathophysiology of these conditions by virtue of its inhibitory effects on IGF activity. Some of the metabolic derangements in type 1 diabetic patients may be due to attenuation of the insulin-like actions of the IGFs (15). Furthermore, it has been suggested that increased levels of IGF inhibitory IGFBPs may play a role in growth impairment in prepubertal children with poorly con-trolled type 1 diabetes and also in late-onset complications of t y p e 1 diabetes, such as retinopathy and nephropathy (16).…”

mentioning

confidence: 99%

Dysregulation of the insulin/IGF binding protein-1 axis in transgenic mice is associated with hyperinsulinemia and glucose intolerance.

2000

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The insulin/IGF binding protein-1 (IGFBP-1) axis is important in coordinating insulin-and IGF-mediated regulation of glucose metabolism and glycemia. Dysregulation of the axis may play a role in the pathophysiology of disorders of insulin deficiency and resistance. We have investigated this hypothesis by generating transgenic mice that overexpress hIGFBP-1. To study the axis in its true physiological context, we used a human (h) IGFBP-1 cosmid clone so that transgene expression is responsive to normal hormonal stimuli. hIGFBP-1 mRNA is expressed in a tissue-specific fashion, and measurement of serum protein levels by specific immunoassay indicates normal physiological regulation in response to fasting/feeding and appropriate post-translational modification as indicated by the detection of phosphorylated and nonphosphorylated isoforms of the protein. The hypoglycemic response to exogenous IGF-I is attenuated in transgenic mice. Transgenic mice exhibit an enhanced insulin secretory response to a glucose challenge, although basal and stimulated blood glucose levels are similar to controls. There is a sexual dimorphism in phenotypic expression: male transgenic mice had higher stimulated glucose and insulin levels than did females. Tr a n s g e n i c mice exhibit fasting hyperglycemia and hyperinsulinemia and glucose intolerance in later life, indicating an age-related decline in glucocompetence. These findings demonstrate the importance of the normal inverse relationship between serum insulin and IGFBP-1 levels in glucoregulation and that sustained dysregulation of the insulin/IGF-I/IGFBP-1 axis is associated with impaired glucose tolerance and abnormalities of insulin action. D i a b e t e s 4 9 :4 5 7-465, 2000

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confidence: 99%

Dysregulation of the insulin/IGF binding protein-1 axis in transgenic mice is associated with hyperinsulinemia and glucose intolerance.

2000

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“…The levels of IGF-I in group A were significantly lower than those in groups B and C, and IGF-I SDS in group A were significantly lower than those in group B. The levels of IGFBP-1 in all three groups were significantly higher than those in our control data [3]. The levels of tGHBP, cGHBP and fGHBP in the three groups were not significantly different.…”

mentioning

confidence: 49%

“…low GHBP in circulation. We therefore suggest that low level GHBP, especially the free form, may plays a definitive role in low production of IGF-I which may be further affected by hyperglycemia and high IGFBP-1 [3,9], resulting in high GH in children and adolescents with IDDM.…”

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confidence: 99%

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The Involvement of Growth Hormone-Binding Protein in Altered GH-IGF Axis in IDDM

et al. 1999

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Abstract. High GH and low IGF-I are well known in IDDM patients. To delineate this altered GH-IGF-I axis in IDDM, we investigate the role of GH-binding protein (GHBP) in relation to the metabolic and nutritional states. Materials and Methods: Forty seven patients with IDDM, mean 13.7 years, were evaluated. Blood samples were obtained before insulin injection and breakfast to test for plasma glucose (PG), IGF-I, IGFBP-1, IGFBP-3, total and complex GHBP (tGHBP and cGHBP), and HbA1C. Urine samples were collected in the morning for urinary GH (uGH). The difference between tGHBP and cGHBP is defined as fGHBP. The levels of PG and HbA1c were not correlated with each level of tGHBP, cGHBP, fGHBP or uGH. The levels of tGHBP, cGHBP and fGHBP were not all correlated with uGH. Both the levels of IGF-I and body mass index (BMI) were positively correlated with (GHBP. The duration of IDDM was negatively correlated with tGHBP, cGHBP and fGHBP. Discussion: As the previous report of the relationship between GH binding reserve to GHBP and IGF-I or BMI in nondiabetic subjects, fGHBP again showed statistical links with these parameters in IDDM. We therefore suggest that GHBP, especially its free form, may reflect a malmetabolic state of IDDM liver, resulting in an altered GH-IGF-I axis.

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“…The term "dawn phenomenon" was introduced in 1981 by Schmidt et al [1] to describe hyperglycemia or an increase for insulin needed to maintain normoglycemia, occurring during the early morning hours. Subsequently, based on the results of published studies [51][52][53][54][55] and clinical experience, investigators suggested that the magnitude of the dawn increase in plasma glucose level should be more than 10 mg/dL, or the increase in insulin requirement should be at least 20% of the overnight nadir, in order to fulfill quantitative criteria for the occurrence of the dawn phenomenon.…”

Section: Effects Of Growth Hormone On Dawn Phenomenon In Type 2 Diabetesmentioning

confidence: 99%

Effects of Growth Hormone on Diurnal Insulin Sensitivity in Normal and Type 2 Diabetic Patients and Animal Models

Shih¹,

Ho²

2016

J Diabetes Metab

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This review addresses the effects of growth hormone on diurnal insulin sensitivity in normal, patients with type 2 diabetes mellitus (T2DM) and animal models described in our previous studies. Results confirmed the presence of diurnal insulin sensitivity, or greater insulin sensitivity in the morning, in normal subjects. The exact cause of this circadian rhythm in plasma glucose levels in healthy subjects has not been established, and nocturnal surges in growth hormone secretion remain a possible explanation. Results showed that growth hormone is an important factor controlling the diurnal variation of glucose tolerance and insulin sensitivity in rats. Data from our previous study provided direct evidence that the role of growth hormone in regulating insulin sensitivity in healthy subjects may be related to changes in the metabolic clearance rate of insulin and the metabolism of non-esterified fatty acids. A different circadian rhythm for plasma glucose appears to be present in patients with T2DM with nadirs in the early evening and peaks in the early morning, indicating greater insulin sensitivity in the evening. As in normal subjects, the exact cause of these circadian rhythms in the plasma glucose levels of patients with T2DM provided direct evidence that the reduction in insulin sensitivity may be due to the nocturnal surge of growth hormone in the early morning hours.

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Role of IGF Binding Protein- 1 in the Dawn Phenomenon and Glycemic Control in Children and Adolescents With IDDM

Cited by 29 publications

References 31 publications

Dysregulation of the insulin/IGF binding protein-1 axis in transgenic mice is associated with hyperinsulinemia and glucose intolerance.

Dysregulation of the insulin/IGF binding protein-1 axis in transgenic mice is associated with hyperinsulinemia and glucose intolerance.

The Involvement of Growth Hormone-Binding Protein in Altered GH-IGF Axis in IDDM

Effects of Growth Hormone on Diurnal Insulin Sensitivity in Normal and Type 2 Diabetic Patients and Animal Models

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