Evidence for the Presence of Type I Insulin-Like Growth Factor Receptors on Rat Pancreatic A and B Cells*

Schravendijk, C. F. H. Van; Foriers, Andére; Brande, J. L. Van den; Pipeleers, Daniël

doi:10.1210/endo-121-5-1784

Cited by 111 publications

(64 citation statements)

References 34 publications

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“…Inhibition of IR and EGFR signaling up-regulates GLP1R-mediated signaling in pancreatic β-cells Pancreatic β-cells are known to express many types of RTKs such as IR, IGF1R, and EGFR (Harbeck et al, 1996;Huotari et al, 1998;Van Schravendijk et al, 1987). To investigate involvement of RTK signaling in the control of the GLP1R-mediated signaling cascade, INS-1 cells, rat pancreatic β-cells, were pretreated with the IGFR inhibitor JBI, the EGFR inhibitor AG1478, and the IR inhibitor HNMPA for 2 h prior to treatment with exe-4, a GLP-1 agonist.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, there is a possibility that the IR and EGFR in β-cells under cultured condition can be continuously activated by insulin secreted from β-cells and serum components of the media. Although β-cells are known to express IGFR (Van Schravendijk et al, 1987), the contribution of IGFR-mediated signaling to GLP-1 response is likely marginal under cultured condition.…”

Section: Resultsmentioning

confidence: 99%

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Insulin Contributes to Fine-Tuning of the Pancreatic Beta-Cell Response to Glucagon-Like Peptide-1

Moon

Kim

Park

et al. 2011

Molecules and Cells

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Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion from pancreatic β-cells in a glucose-dependent manner. However, factors other than glucose that regulate the β-cell response to GLP-1 remain poorly understood. In this study, we examined the possible involvement of insulin and receptor tyrosine kinase signaling in regulation of the GLP-1 responsiveness of β-cells. Pretreatment of β-cells with HNMPA, an insulin receptor inhibitor, and AG1478, an epidermal growth factor receptor inhibitor, further increased the cAMP level and Erk phosphorylation in the presence of exendin-4 (exe-4), a GLP-1 agonist. When β-cells were exposed to a high concentration of glucose (25 mM), which stimulates insulin secretion, exe-4-induced cAMP formation declined gradually as exposure time was increased. This decreased cAMP formation was not observed in the presence of HNMPA. HNMPA was able to further increase the exe-4-induced insulin secretion when β-cells were exposed to high glucose for 18 h. Treatment of β-cells with insulin significantly decreased exe-4-induced cAMP formation in a dose-dependent manner. Lowering the phospho-Akt level by HNMPA or LY294002, a PI3K inhibitor, further augmented exe-4-induced cAMP formation and Erk phosphorylation. These results suggest that insulin contributes to fine-tuning of the β-cell response to GLP-1.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Insulin Contributes to Fine-Tuning of the Pancreatic Beta-Cell Response to Glucagon-Like Peptide-1

Moon

Kim

Park

et al. 2011

Molecules and Cells

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“…Increased IGF-I expression is also localized to focal areas of regeneration in pancreatectomized rats and dogs (16,17), suggesting that IGF-I contributes to the growth or differentiation of pancreatic tissue. Islet cells contain IGF-I receptors (18). Mice lacking both IGF-I receptors and insulin receptor substrate-2 (IRS-2) show marked reduction of β cell mass and die from diabetes due to β cell insufficiency (19), indicating that IGF-I receptors couple to IRS-2 in the pancreatic islet to mediate β cell development, proliferation, and survival.…”

Section: Introductionmentioning

confidence: 99%

β cell expression of IGF-I leads to recovery from type 1 diabetes

George¹,

Ayuso²,

Casellas³

et al. 2002

J. Clin. Invest.

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Patients with type 1 diabetes are identified after the onset of the disease, when β cell destruction is almost complete. β cell regeneration from islet cell precursors might reverse this disease, but factors that can induce β cell neogenesis and replication and prevent a new round of autoimmune destruction remain to be identified. Here we show that expression of IGF-I in β cells of transgenic mice (in both C57BL/6-SJL and CD-1 genetic backgrounds) counteracts cytotoxicity and insulitis after treatment with multiple low doses of streptozotocin (STZ). STZ-treated nontransgenic mice developed high hyperglycemia and hypoinsulinemia, lost body weight, and died. In contrast, STZtreated C57BL/6-SJL transgenic mice showed mild hyperglycemia for about 1 month, after which they normalized glycemia and survived. After STZ treatment, all CD-1 mice developed high hyperglycemia, hypoinsulinemia, polydipsia, and polyphagia. However, STZ-treated CD-1 transgenic mice gradually normalized all metabolic parameters and survived. β cell mass increased in parallel as a result of neogenesis and β cell replication. Thus, our results indicate that local expression of IGF-I in β cells regenerates pancreatic islets and counteracts type 1 diabetes, suggesting that IGF-I gene transfer to the pancreas might be a suitable therapy for this disease.

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“…The effect of insulin is most prominent at rather high concentrations being present in the intercellular space of pancreatic B-cells which is in favour of an interaction of insulin with IGF-1 receptors as was postulated by Schravendijk [22,23]. PAO reversed the inhibition of insulin release in the case of both insulin and IGF-1.…”

Section: Discussionmentioning

confidence: 80%

“…Since insulin effects are generally affected by PAO as was mentioned before, PAO effects on insulin-modulated insulin release were investigated using INS-1 cells, an insulin secreting cell line. Since there is an interaction between PAO and IGF-1 and since IGF-1 receptors may be involved in insulin negative feedback effects on insulin release [22,23], the interaction between IGF-1 and PAO was investigated as well.…”

mentioning

confidence: 99%

Effect of PAO (phenylarsine oxide) on the Inhibitory Effect of Insulin and IGF-1 on Insulin Release from INS-1 Cells

Verspohl

2006

Endocr J

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Abstract. Phenylarsine oxide (PAO) which complexes vicinal thiol groups is a valuable pharmacological tool to investigate the interaction of peptides such as insulin with their receptors and the signal transduction from the receptor to the cell interior. This tool was now used to elucidate the inhibitory effects of insulin and IGF-1 on insulin secretion via their receptors. Insulin and IGF-1 inhibited insulin release from INS-1 cells, an insulin secreting cell line. PAO was able to reverse this inhibitory effect of both hormones. Dimercaptopropanol (DMP), which is well known to antagonize PAO effects, inhibited the abolishment of PAO effect on the inhibitory effect of insulin and IGF-1 regarding insulin release. Membrane bound GLUT2 in INS-1 cells was increased by either insulin and IGF-1 which is counteracted by PAO. Thus the inhibitory effect of insulin and IGF-1 on insulin release is operative and can be disturbed by a thiol interacting compound such as PAO. This may happen at the receptor level or at the sub-receptor level. [6][7][8] e.g. in the presence of vanadate; PAO thereby probably bypasses the direct effects on the insulin receptor and will interact with the components of insulin signal transduction [9,10]. With respect to biological effects there is an (a) Inhibition of insulin effect on various parameters and enzymes (fructose 2,6-biphosphate, phosphofructokinase, glucokinase, glycolysis, glycogen synthesis, amino acid transport, glycogenolysis, proteolysis) (b) Inhibition of glucose transport even under conditions when insulin receptor binding/autophosphorylation is not influenced [11][12][13]; inhibition of IGF-1 -induced glucose transport (c) Decrease in GLUT4 [14], albeit no down-regulation of the GLUT1 transporter and inhibition of the insulin-induced dephosphorylation of GLUT4 (d) Increase in amino acid uptake [15] (e) Inhibition of the insulin-induced PP-1 activation and inhibition of phosphotyrosine phosphatase (GAP-phosphorylation on tyrosine (p21 ras-GTPase activation protein), increased GAP-association with the insulin receptor, inhibition of insulininduced p21 ras activation) [16] (f) inhibition of PI3-kinase a which is recruited from IRS-1 (insulin receptor substrate 1) tyrosine phosphorylation [17].

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Evidence for the Presence of Type I Insulin-Like Growth Factor Receptors on Rat Pancreatic A and B Cells*

Cited by 111 publications

References 34 publications

Insulin Contributes to Fine-Tuning of the Pancreatic Beta-Cell Response to Glucagon-Like Peptide-1

Insulin Contributes to Fine-Tuning of the Pancreatic Beta-Cell Response to Glucagon-Like Peptide-1

β cell expression of IGF-I leads to recovery from type 1 diabetes

Effect of PAO (phenylarsine oxide) on the Inhibitory Effect of Insulin and IGF-1 on Insulin Release from INS-1 Cells

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