Pancreatic Beta-cell growth and diabetes mellitus

Swenne, Ingemar

doi:10.1007/bf00400917

Cited by 189 publications

(124 citation statements)

References 89 publications

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“…Whereas IAPP mRNA expression is increased at the cellular level, insulin mRNA expression is actually down regulated by dexamethasone treatment. In accordance with previous studies [65], we noticed a marked hyperplasia and hypertrophy of islet cells in the treated rats; this increase in islet mass explains that although insulin mRNA expression at the cellular level decreases, the total islet expression of insulin still increases twofold.…”

Section: Overexpression Of Iapp In Experimental Diabetessupporting

confidence: 93%

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Islet amyloid polypeptide in the islets of Langerhans: friend or foe?

2000

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Section: Overexpression Of Iapp In Experimental Diabetessupporting

confidence: 93%

“…Given the expression of IAPP in non-beta cells [64] as well as the proliferative effects of glucocorticoids in islets [65], we extended the studies on IAPP and insulin expression in experimental diabetes using cellular analysis (Fig. 2).…”

Section: Overexpression Of Iapp In Experimental Diabetesmentioning

confidence: 99%

Islet amyloid polypeptide in the islets of Langerhans: friend or foe?

2000

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“…37 The positive correlation found between age and b-cell replication 37 suggests that replication plays an active role in the maintenance of b-cell mass, and that defects in b-cell replication could also contribute to b-cell mass reduction in type II diabetes. 38,39 Accordingly, insufficient b-cell replication has been reported in several experimental models of diabetes, such as male OLETF rats, 40 STZ-treated neonatal rats 41 or the desert gerbil Psammomys obesus. 33 Recent data describing the expression of IL-1b in islets from type II diabetic patients and the glucose-induced production and release of IL-1b in cultured human islets suggest that IL-1b plays a role in type II diabetes.…”

Section: Discussionmentioning

confidence: 99%

Adenoviral overexpression of interleukin-1 receptor antagonist protein increases β-cell replication in rat pancreatic islets

et al. 2004

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The naturally occurring inhibitor of interleukin-1 (IL-1) action, interleukin-1 receptor antagonist protein (IRAP), binds to the type 1 IL-1 receptor but does not initiate IL-1 signal transduction. In this study, we have determined the effects of IL-1b and IRAP overexpression on adult b-cell replication and viability. IL-1b reduced dramatically b-cell replication in adult rat islets both at 5.5 mM (control: 0.2970.04%; IL-1b: 0.0270.02%, Po0.05) and 22.2 mM glucose (control: 0.8470.2%; IL-1b: 0.0570.05%, Po0.05). This effect was completely prevented in islets overexpressing IRAP after adenoviral gene transfer at 5.5 mM (Ad-IL-1Ra+IL-1b: 0.8470.1%, Po0.05) and 22.2 mM glucose (Ad-IL-1Ra+IL-1b: 1.2270.2%, Po0.05). Moreover, overexpression of IRAP increased glucose-stimulated b-cell replication in the absence of IL-1b exposure (Ad-IL-1Ra: 1.5970.5%, Po0.05). b-Cell death (TUNEL technique) was increased in IL-1b-exposed islets but not in Ad-IL-1Ra-infected islets (control: 0.8270.2%; control+IL-1b: 1.7770.2; IRAP: 0.6170.2%; IRAP+IL-1b: 0.8670.1%, Po0.05). Comparable results were obtained by flow cytometry. To determine the effect of IRAP overexpression on b-cell replication in vivo, Ad-IL-1Ra-transduced islets were transplanted into streptozotocin diabetic rats. b-Cell replication was significantly increased in IRAP-overexpressing islet grafts (0.9870.3%, Po0.05) compared to normal pancreas (0.3570.02%), but not in control islet grafts (0.5070.1%). This study shows that in addition to the effects of IL-1b on bcell viability, this cytokine exerts a deleterious action on b-cell replication, which can be prevented by IRAP overexpression, and provides support for the potential use of IRAP as a therapeutic tool. Gene Therapy (2005) 12, 120-128.

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“…Serum IGF-1 levels, mainly of hepatic origin, are predominantly regulated by growth hormone. In the developing pancreas, IGF-1 and IGF-2 are produced by cells of the islets of Langerhans where they exert paracrine and autocrine functions critical for islet differentiation (9) and islet cell growth (10,11). IGF-2 supports fibroblast growth factor (FGF)-2-mediated islet growth (12), whereas IGF-1 has been shown to directly protect b-cells from apoptosis (13,14).…”

Section: Introductionmentioning

confidence: 99%

Repression of Malignant Tumor Progression upon Pharmacologic IGF1R Blockade in a Mouse Model of Insulinoma

Zumsteg

Caviezel²,

Pisarsky³

et al. 2012

Molecular Cancer Research

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NVP-AEW541, a specific ATP-competitive inhibitor of the insulin-like growth factor-1 receptor (IGF1R) tyrosine kinase, has been reported to interfere with tumor growth in various tumor transplantation models. We have assessed the efficacy of NVP-AEW541 in repressing tumor growth and tumor progression in the Rip1Tag2 transgenic mouse model of pancreatic b-cell carcinogenesis. In addition, we have tested NVP-AEW541 in Rip1Tag2;RipIGF1R double-transgenic mice which show accelerated tumor growth and increased tumor malignancy compared with Rip1Tag2 single-transgenic mice. Previously, we have shown that high levels of IGF-2, a high-affinity ligand for IGF1R, are required for Rip1Tag2 tumor cell survival and tumor growth. Unexpectedly, treatment of Rip1Tag2 mice with NVP-AEW541 in prevention and intervention trials neither did affect tumor growth nor tumor cell proliferation and apoptosis. Yet, it significantly repressed progression to tumor malignancy, that is, the rate of the transition from differentiated adenoma to invasive carcinoma. Treatment of Rip1Tag2;RipIGF1R double-transgenic mice resulted in moderately reduced tumor volumes and increased rates of tumor cell apoptosis. Sustained expression of IGF-2 and of the IGF-2-binding form of insulin receptor (IR-A) in tumor cells suggests a compensatory role of IR-A upon IGF1R blockade. The results indicate that inhibition of IGF1R alone is not sufficient to efficiently block insulinoma growth and imply an overlapping role of IGF1R and insulin receptor in executing mitogenic and survival stimuli elicited by IGF-2.

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Pancreatic Beta-cell growth and diabetes mellitus

Cited by 189 publications

References 89 publications

Islet amyloid polypeptide in the islets of Langerhans: friend or foe?

Islet amyloid polypeptide in the islets of Langerhans: friend or foe?

Adenoviral overexpression of interleukin-1 receptor antagonist protein increases β-cell replication in rat pancreatic islets

Repression of Malignant Tumor Progression upon Pharmacologic IGF1R Blockade in a Mouse Model of Insulinoma

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