Serum IRI in insulin-treated diabetics during a 24-hour period

Rasmussen, Stig Munkgaard; Hedïng, Lise G.; Parbst, E; Vølund, Aage

doi:10.1007/bf00429840

Cited by 42 publications

(2 citation statements)

References 23 publications

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“…Epidemiologic data have suggested a role of hyperinsulinemia as an independent risk factor for the development of atherosclerosis (12)(13)(14). Moreover, the significantly higher incidence of atherosclerosis among patients with diabetes mellitus (15,16) and the recognition that patients on insulin treatment tend to have elevated insulin levels in the systemic circulation (17,18) make this issue of critical concern.…”

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confidence: 99%

Characterization of Induction of Protooncogene c-myc and Cellular Growth in Human Vascular Smooth Muscle Cells by Insulin and IGF-I

Banskota

Taub²,

Zellner³

et al. 1989

Diabetes

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Insulin and insulin-like growth factor I (IGF-I) are structurally related polypeptides that stimulate DNA synthesis and cellular proliferation, probably through a common pathway. Human arterial smooth muscle cells in culture demonstrated the presence of high-affinity receptors for both these hormones. Insulin and IGF-I both exhibited cross-reactivity to each other's receptors but with an affinity that is 100-fold less than for the homologous receptor. To examine more closely the receptor responsible for producing the growth effects, we used the polyclonal antibody against the insulin receptor, B2, and a monoclonal antibody to the IGF-I receptor, αIR3 . We studied the growth effects of insulin and IGF-I as measured by stimulation of c-myc, DNA synthesis, and cellular proliferation in the presence and absence of these antibodies. F(ab') fragments of the anti-insulin-receptor antibody at a concentration of 10 μg/ml were capable of displacing >90% of the bound insulin, thus establishing an effective insulin-receptor blockade. Under such blockade, insulin and IGF-I were both capable of doubling the amount of DNA synthesis and cell number in cultured human arterial smooth muscle cells. However, in the presence of a 1:2500 dilution of the monoclonal antibody αlR3 , which caused a 90% displacement of IGF-I bound to its receptor, both the insulin and IGF-I effects on stimulating DNA synthesis or cellular proliferation were inhibited by >90%. These findings demonstrate that the IGF-I receptor is the common pathway for the growth effects of both insulin and IGF-I. Induction of the protooncogene c-myc is recognized as an early response to many mitogenic stimuli. In human smooth muscle cells, insulin (1 × 10−7M) and IGF-I (1 × 10−9M) both cause a 5- to 10-fold increase in c-myc mRNA levels. Induction of c-myc could not be assessed under conditions of selective IGF-I-receptor blockade with the antibody αIR3, because, surprisingly, the antibody itself stimulated c-myc mRNA levels. This induction of c-myc with αIR3, which does not increase DNA synthesis or cellular proliferation, suggests that c-myc induction does not entirely correlate with the growth effects of these hormones.

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confidence: 99%

Characterization of Induction of Protooncogene c-myc and Cellular Growth in Human Vascular Smooth Muscle Cells by Insulin and IGF-I

Banskota

Taub²,

Zellner³

et al. 1989

Diabetes

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“…Heding and her colleagues have shown well the sluggish response of free insulin concentrations to therapy in patients who have anti-insulin antibodies [30]. It is thus theoretically likely that patients with no or low antibodies will have a more desirable free insulin pattern.…”

mentioning

confidence: 99%