Exaggerated growth hormone response to growth hormone-releasing hormone in type I diabetes mellitus

Krassowski, J; Felber, J. P.; Rogala, H; Jeske, W; Zgliczyński, S

doi:10.1530/acta.0.1170225

Cited by 41 publications

(26 citation statements)

References 4 publications

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“…This hypothesis is consistent with a report showing BALB/c mice, when treated with a single i.v. injection of HI STZ (250-300 mg/kg), have elevated circulating GH levels, which was associated with hypoinsulinemia and hyperglycemia without dramatic weight loss or ketosis (Flyvbjerg et al 1999), a response similar to that reported in poorly controlled type I diabetic humans (Cohen & Abplanalp 1991, Ismail et al 1993, Krassowski et al 1988). However, from these studies it is difficult to say with certainty if the variable effects of STZ on circulating GH levels are due to the severity of catabolic condition or if the differences are more related to species or genetic background of the animal model used.…”

Section: Introductionsupporting

confidence: 63%

“…Comparable changes in pituitary sensitivity to GH secretagogues are observed in patients with uncontrolled insulin-dependent diabetes (Catalina et al 1998, Krassowski et al 1988). Therefore, it is possible that the enhanced GH output observed in the insulin-dependent diabetic human (Catalina et al 1998, Krassowski et al 1988) may be related, at least in part, to changes in pituitary receptor expression that would favor GH release. It has also been hypothesized that the characteristic reduction in circulating IGF-I and insulin, both known inhibitors of GH synthesis and release (Yamashita & Melmed 1986a, 1986b, could enhance GH output in insulinopenic diabetes (Bereket et al 1999).…”

Section: Discussionmentioning

confidence: 98%

“…In addition, STZ-treated mice have been reported to display enhanced GH responses to the GHS-R ligand ipamorelin (Johansen et al 2003). Comparable changes in pituitary sensitivity to GH secretagogues are observed in patients with uncontrolled insulin-dependent diabetes (Catalina et al 1998, Krassowski et al 1988). Therefore, it is possible that the enhanced GH output observed in the insulin-dependent diabetic human (Catalina et al 1998, Krassowski et al 1988) may be related, at least in part, to changes in pituitary receptor expression that would favor GH release.…”

Section: Discussionmentioning

confidence: 99%

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Differential responses of the growth hormone axis in two rat models of streptozotocin-induced insulinopenic diabetes

Kim¹,

Sohn²,

Lee³

et al. 2006

Journal of Endocrinology

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The impact of streptozotocin (STZ)-induced, insulinopenic diabetes on the GH axis of rats and mice differs from study to study, where this variation may be related to the induction scheme, severity of the diabetes and/or the genetic background of the animal model used. In order to begin differentiate between these possibilities, we compared the effects of two different STZ induction schemes on the GH axis of male Sprague-Dawley rats: (1) a single high-dose injection of STZ (HI STZ, 80 mg/kg, i.p.), which results in rapid chemical destruction of the pancreatic -cells, and (2) multiple low-dose injections of STZ (LO STZ, 20 mg/kg for 5 consecutive days, i.p.), which results in a gradual, autoimmune destruction of -cells. STZ-treated animals were killed after 3 weeks of hyperglycemia (>400 mg/dl), and in both paradigms circulating insulin levels were reduced to <40% of vehicle-treated controls. HI STZ-treated rats lost weight, while body weights of LO STZ-treated animals gradually increased over time, similar to vehicle-treated controls. As previously reported, HI STZ resulted in a decrease in circulating GH and IGF-I levels which was associated with a rise in hypothalamic neuropeptide Y (NPY) mRNA (355% of vehicle-treated controls) and a fall in GH-releasing hormone (GHRH) mRNA (45% of vehicle-treated controls) levels. Changes in hypothalamic neuropeptide expression were reflected by an increase in immunoreactive NPY within the arcuate and paraventricular nuclei and a decrease in GHRH immunoreactivity in the arcuate nucleus, as assessed by immunohistochemistry. Consistent with the decline in circulating GH and hypothalamic GHRH, pituitary GH mRNA levels of HI STZ-treated rats were 58% of controls. However, pituitary receptor mRNA levels for GHRH and ghrelin increased and those for somatostatin (sst2, sst3 and sst5) decreased following HI STZ treatment. The impact of LO STZ treatment on the GH axis differed from that observed following HI STZ treatment, despite comparable changes in circulating glucose and insulin. Specifically, LO STZ treatment did suppress circulating IGF-I levels to the same extent as HI STZ treatment; however, the impact on hypothalamic NPY mRNA levels was less dramatic (158% of vehicle-treated controls) where NPY immunoreactivity was increased only within the paraventricular nucleus. Also, there were no changes in circulating GH, hypothalamic GHRH or pituitary receptor expression following LO STZ treatment, with the exception that pituitary sst3 mRNA levels were suppressed compared with vehicle-treated controls. Taken together these results clearly demonstrate that insulinopenia, hyperglycemia and reduced circulating IGF-I levels are not the primary mediators of hypothalamic and pituitary changes in the GH axis of rats following HI STZ treatment. Changes in the GH axis of HI STZ-treated rats were accompanied by weight loss, and these changes are strikingly similar to those observed in the fasted rat, which suggests that factors associated with the catabolic state are critical in modify...

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Section: Introductionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Differential responses of the growth hormone axis in two rat models of streptozotocin-induced insulinopenic diabetes

Kim¹,

Sohn²,

Lee³

et al. 2006

Journal of Endocrinology

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show abstract

“…Humans with type 1 (insulin-dependent) diabetes mellitus have higher spontaneous [1] and stimulated [2] GH secretion with respect to normal subjects. Moreover, type 1 diabetic patients have been reported to have an exaggerated GH response to growth hormone-releasing hormone (GHRH) [3][4][5]. This GH hypersecretion has Received: October 9, 1990 Accepted after revision: July 24.…”

mentioning

confidence: 99%

Hypothalamic Regulation of Impaired Growth Hormone Secretion in Diabetic Rats

1992

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Growth hormone (GH) secretion is blunted in diabetic rats. In the present experiment we observed that pituitary GH concentrations and the plasma GH response to an exogenous dose of growth hormone-releasing hormone (GHRH) is decreased in streptozotocin-induced diabetic rats (p < 0.02) with respect to normal rats. In an attempt to determine if increased somatostatin (SRIF) secretion is responsible for the decreased GH secretion, we studied the effect of modulating SRIF tone on the GH response to GHRH in normal and streptozotocin-induced diabetic rats. Rats were pretreated with either normal sheep serum and saline (NSS + SAL), somatostatin antibodies (SRIF-Ab), or pyridostigmine (PD), an acetylcholinesterase inhibitor hypothesized to reduce hypothalamic SRIF secretion. Pretreatment of normal rats with SRIF-Ab or PD resulted in an increased GH response to exogenous GHRH in comparison to NSS + SAL-pretreated normal rats at 5 min postinjection. In contrast, pretreatment of diabetic rats with SRIF-Ab or PD did not alter the GH response to exogenous GHRH when compared to NSS + SAL-pretreated diabetic animals. These results suggest that the blunted GH response to exogenous GHRH observed in streptozotocin-induced diabetic rats may not be due to an increase of endogenous SRIF tone.

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“…Studies in humans have provided evidence of apparent resistance to the effects of somatostatin (22) and impaired auto-feedback by which endogenous GH inhibits its own secretion (23). An exaggerated GH response to GHRH has also been reported (24). Furthermore, subjects with IDDM do not show the normal inhibition of GH secretion with hyperglycaemia (25) and it has been suggested that they have a defect in hypothalamic somatostatin regulation of GH secretion.…”

Section: Metabolic Effects Of Gh Hypersecretionmentioning

confidence: 95%

Effects of rh Insulin-like Growth Factor I (IGF-I) Treatment on Growth Hormone (GH) Hypersecretion in Adolescents with Type 1 Diabetes

Dunger

Cheetham

1994

Clin Pediatr Endocrinol

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Exaggerated growth hormone response to growth hormone-releasing hormone in type I diabetes mellitus

Cited by 41 publications

References 4 publications

Differential responses of the growth hormone axis in two rat models of streptozotocin-induced insulinopenic diabetes

Differential responses of the growth hormone axis in two rat models of streptozotocin-induced insulinopenic diabetes

Hypothalamic Regulation of Impaired Growth Hormone Secretion in Diabetic Rats

Effects of rh Insulin-like Growth Factor I (IGF-I) Treatment on Growth Hormone (GH) Hypersecretion in Adolescents with Type 1 Diabetes

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