Growth restoration of insulin-deficient diabetic rats by recombinant human insulin-like growth factor I

Scheiwiller, E.; Guler, Hans‐Peter; Merryweather, Jim; Scandella, Carl J.; Maerki, W.; Zapf, J.; Froesch, E. R.

doi:10.1038/323169a0

Cited by 189 publications

(102 citation statements)

References 25 publications

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“…The mechanisms involved in this apparent resistance to GH are not known. However, the observations reported by Scheiwiller et al, [25] that administration of IGF-I is able to stimulate growth in diabetic rats supports the hypothesis that the major defect is in activation of IGF-I expression. The data reported here support the hypothesis that there is a defect in IGF-I gene activation in the diabetic rat effecting not only growth hormone-induced IGF-I expression but also IGF-I gene activation in response to another stimuli.…”

Section: Discussioncontrasting

confidence: 46%

Impaired estrogen-induced uterine insulin-like growth factor-I gene expression in the streptozotocin diabetic rat

Murphy

1988

Diabetologia

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Section: Discussioncontrasting

confidence: 46%

Impaired estrogen-induced uterine insulin-like growth factor-I gene expression in the streptozotocin diabetic rat

Murphy

1988

Diabetologia

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“…Serum insulin-like growth factor 1 (IGF1) levels were significantly decreased in ␤GsKO mice compared with control and E1 fl/ϩ :cre ϩ mice, and this may be an important contributing factor to the poor linear growth in these mice. Insulin has been shown to regulate the expression of both IGF1 and its binding proteins, and poor growth in insulindeficient diabetics has been ascribed to low IGF1 levels (18)(19)(20)(21)(22)(23). Therefore, the poor growth and low IGF1 levels observed in ␤GsKO mice may be secondary to hypoinsulinemia, although reduced growth hormone secretion from the pituitary is another potential contributing factor.…”

Section: Resultsmentioning

confidence: 97%

“…Insulin induces IGF1 expression and poor growth in diabetics with low IGF1 levels is reversed by IGF1 replacement (18)(19)(20)(21)(22)(23). Therefore, hypoinsulinemia may account for the low IGF1 levels and poor growth in ␤GsKO mice.…”

Section: Discussionmentioning

confidence: 99%

β cell-specific deficiency of the stimulatory G protein α-subunit G _s α leads to reduced β cell mass and insulin-deficient diabetes

Xie

Chen

Zhang

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The G protein ␣-subunit Gs␣ is required for hormone-stimulated cAMP generation. In pancreatic ␤ cells, Gs␣ mediates the signaling of glucagon-like peptide 1 and other incretin hormones, which are implicated as important regulators of ␤ cell survival and insulin release. Studies have suggested that G s␣/cAMP mediates these actions by stimulating insulin receptor substrate 2 (IRS2) expression. Mice with ␤ cell-specific Gs␣ deficiency (␤GsKO) were generated by mating G s␣-floxed mice to rat insulin II promoter-cre recombinase mice. ␤GsKO mice had poor survival and postnatal growth with low serum insulin-like growth factor 1 levels. ␤GsKO mice also developed severe hyperglycemia and glucose intolerance with severe hypoinsulinemia and reduced islet insulin content and glucose-stimulated insulin release. ␤GsKO mice had markedly reduced average islet size and ␤ cell mass, which was partially explained by reduced ␤ cell size. In addition, ␤GsKO mice had significantly reduced ␤ cell proliferation and increased ␤ cell apoptosis and markedly reduced expression of the cell cycle protein cyclin D2. The effects on ␤ cell mass and proliferation, but not apoptosis, were present from birth. Unexpectedly expression of Irs2 and the downstream gene Pdx1 were unaffected. These results show that G s␣/cAMP pathways are critical regulators of ␤ cell function and proliferation that can work through IRS2-independent mechanisms.

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“…In this scenario (Fig. 8), an increased circulating insulin level (in response to an elevated nutrient level and hormonal action) will act on the liver and perhaps other tissues to stimulate the synthesis of IGF-1 (29,30). IGF-1 then will in turn bind to its own receptors on the ␤ cell surface, thereby activating PDE3B and decreasing cAMP.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of insulin secretion by insulin-like growth factor 1 is mediated through activation of phosphodiesterase 3B

Zhao

Teague

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

138

115

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Both insulin and insulin-like growth factor 1 (IGF-1) are known to reduce glucose-dependent insulin secretion from the ␤ cells of pancreatic islets. In this paper we show that the mechanism by which IGF-1 mediates this effect is in large part through activation of a specific cyclic nucleotide phosphodiesterase, phosphodiesterase 3B (PDE3B). More specifically, in both isolated pancreatic islets and insulin-secreting HIT-T15 cells, IGF-1 inhibits insulin secretion that has been increased by glucose and glucagonlike peptide 1 (GLP-1). Moreover, IGF-1 decreases cAMP levels in parallel to the reduction of insulin secretion. Insulin secretion stimulated by cAMP analogs that activate protein kinase A and also are substrates for PDE3B is also inhibited by IGF-1. However, IGF-1 does not inhibit insulin secretion stimulated by nonhydrolyzable cAMP analogs. In addition, selective inhibitors of PDE3B completely block the ability of IGF-1 to inhibit insulin secretion. Finally, PDE3B activity measured in vitro after immunoprecipitation from cells treated with IGF-1 is higher than the activity from control cells. Taken together with the fact that pancreatic ␤ cells express little or no insulin receptor but large amounts of IGF-1 receptor, these data strongly suggest a new regulatory feedback loop model for the control of insulin secretion. In this model, increased insulin secretion in vivo will stimulate IGF-1 synthesis by the liver, and the secreted IGF-1 in turn feedback inhibits insulin secretion from the ␤ cells through an IGF-1 receptormediated pathway. This pathway is likely to be particularly important when levels of both glucose and secretagogues such as GLP-1 are elevated.

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Growth restoration of insulin-deficient diabetic rats by recombinant human insulin-like growth factor I

Cited by 189 publications

References 25 publications

Impaired estrogen-induced uterine insulin-like growth factor-I gene expression in the streptozotocin diabetic rat

Impaired estrogen-induced uterine insulin-like growth factor-I gene expression in the streptozotocin diabetic rat

β cell-specific deficiency of the stimulatory G protein α-subunit G _s α leads to reduced β cell mass and insulin-deficient diabetes

Attenuation of insulin secretion by insulin-like growth factor 1 is mediated through activation of phosphodiesterase 3B

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Growth restoration of insulin-deficient diabetic rats by recombinant human insulin-like growth factor I

Cited by 189 publications

References 25 publications

Impaired estrogen-induced uterine insulin-like growth factor-I gene expression in the streptozotocin diabetic rat

Impaired estrogen-induced uterine insulin-like growth factor-I gene expression in the streptozotocin diabetic rat

β cell-specific deficiency of the stimulatory G protein α-subunit G s α leads to reduced β cell mass and insulin-deficient diabetes

Attenuation of insulin secretion by insulin-like growth factor 1 is mediated through activation of phosphodiesterase 3B

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β cell-specific deficiency of the stimulatory G protein α-subunit G _s α leads to reduced β cell mass and insulin-deficient diabetes