Insulin Receptor Number and Binding Affinity in Newborn Dogs

Johnston, V.; Frazzini, Vincent I.; Davidheiser, Sandra; Przybylski, Ronald J.; Kliegman, Robert M.

doi:10.1203/00006450-199106010-00017

Cited by 9 publications

(10 citation statements)

References 6 publications

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“…The detection of two insulin binding sites in canine muscle is in agreement with insulin binding data previously described for dogs by Johnston et al (1991). It was proposed that binding of insulin to the S1 of one α-monomer is followed by cross-linking of insulin to the S2' of the alternate α-monomer, with resultant S1/S2' high-affinity binding.…”

Section: Discussionsupporting

confidence: 76%

“…These changes in insulin bin- I-insulin bound (y axis), so the further to the right the curve is, the greater the insulin resistance. These data were inserted in the Ligand sub-directory of Kell for Windows TM version 6 (Biosoft) to generate Kd and Bmax values for both insulin binding sites shown in Table 2. ding characteristics were detected only at the high-affinity binding sites, and it seems that in dogs, low-affinity binding sites are less susceptible to modulation, once Johnston et al (1991), after studying insulin binding properties in different tissues of adult and newborn dogs, also found changes only at high-affinity binding sites.…”

Section: Discussionmentioning

confidence: 99%

“…The interaction between insulin and IR is reversible, and when a system reaches an equilibrium, for each insulin-IR complex formed, another insulin-IR complex dissociates at the same rate. The dissociation constant (Kd) is then considered to be the inverse association constant (Ka), and represents the insulin-free concentration needed to saturate half of the insulin receptors in the system (Sanvitto et al 1994), or in this case, the cold insulin concentration needed to reduce maximal 125 I-insulin binding by 50% (Johnston et al 1991). Therefore, Kd is assumed as a measure of tissue insulin sensitivity, and the higher the Kd, the smaller the insulin sensitivity.…”

Section: Discussionmentioning

confidence: 99%

“…In this scenario, insulin binding studies are useful for evaluating tissue insulin sensitivity (Johnston et al 1991). In dogs, the most common physiological cause of insulin resistance is described in the female dog during the hormonal fluctuations of the estrous cycle.…”

Section: Introductionmentioning

confidence: 99%

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Insulin binding characteristics in canine muscle tissue: effects of the estrous cycle phases

et al. 2016

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Hormonal fluctuations during the different estrous cycle are a well-recognized cause of insulin resistance in bitches, and little is known about insulin receptor binding or post-binding defects associated with insulin resistance in dogs. To evaluate insulin binding characteristics in muscle tissue of bitches during the estrous cycle, 17 owned bitches were used in the study (six in anestrus, five in estrus, and six in diestrus). An intravenous glucose tolerance test (IVGTT) was performed in all patients by means of injection of 1mL/kg of a glucose 50% solution (500mg/kg), with blood sample collection for glucose determination at 0, 3, 5, 7, 15, 30, 45 and 60 minutes after glucose infusion. Muscle samples, taken after spaying surgery, were immediately frozen in liquid nitrogen and then stored at -80 ºC until the membranes were prepared by sequential centrifugation after being homogenized. For binding studies, membranes were incubated in the presence of 20,000cpm of human 125I-insulin and in increasing concentrations of unlabeled human regular insulin for cold saturation. The IVGTT showed no differences among bitches during the estrous cycle regarding baseline glycemia or glycemic response after glucose infusion. Two insulin binding sites - high-affinity and low-affinity ones - were detected by Scatchard analysis, and significant statistical differences were observed in the dissociation constant (Kd1) and maximum binding capacity (Bmax1) of the high-affinity binding sites. The Kd1 for the anestrus group (6.54±2.77nM/mg of protein) was smaller (P<0.001) than for the estrus (28.54±6.94nM/mg of protein) and diestrus (15.56±3.88nM/mg of protein) groups. Bmax1 in the estrus (0.83±0.42nM/mg of protein) and diestrus (1.24±0.24nM/mg of protein) groups were also higher (P<0.001) than the values observed in anestrus (0.35±0.06nM/mg of protein). These results indicate modulation of insulin binding characteristics during different phases of the estrous cycle in dogs, showing that muscle insulin binding affinity for its receptor is reduced during estrus and diestrus. However, this poor hormone-receptor affinity is compensated for by a greater total binding capacity, once there is no difference in patients' glycemic response after an intravenous glucose load.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Insulin binding characteristics in canine muscle tissue: effects of the estrous cycle phases

et al. 2016

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“…The results show that the insulin receptor concentration in skeletal muscle was twofold higher in 7-than in 26-day-old pigs. Studies have shown that insulin receptor abundance in muscle is also higher in suckling than in adult rats and dogs (1,29). However, in those studies, age-related changes in insulin receptor abundance were confounded by changes in diet composition.…”

Section: Effect Of Development On Insulin Receptor Irs-1 and Irs-2 mentioning

confidence: 99%

Developmental changes in the feeding-induced activation of the insulin-signaling pathway in neonatal pigs

Suryawan

Nguyen

Bush

et al. 2001

American Journal of Physiology-Endocrinology and Metabolism

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In neonatal animals, feeding stimulates skeletal muscle protein synthesis, a response that declines with development. Both the magnitude of the feeding response and its developmental decline can be reproduced by insulin infusion, suggesting that an altered responsiveness to insulin is a primary determinant of the developmental decline in the stimulation of protein synthesis by feeding. In this study, 7- and 26-day-old pigs were either fasted overnight or fed porcine milk after an overnight fast. We examined the abundance and degree of tyrosine phosphorylation of the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and IRS-2 in skeletal muscle and, for comparison, liver. We also evaluated the association of IRS-1 and IRS-2 with phosphatidylinositol 3-kinase (PI 3-kinase). The abundance of IR protein in muscle was twofold higher at 7 than at 26 days, but IRS-1 and IRS-2 abundances were similar in muscle of 7- and 26-day-old pigs. The feeding-induced phosphorylations were greater at 7 than at 26 days of age for IR (28- vs. 13-fold), IRS-1 (14- vs. 8-fold), and IRS-2 (21- vs. 12-fold) in muscle. The associations of IRS-1 and IRS-2 with PI 3-kinase were also increased by refeeding to a greater extent at 7 than at 26 days (9- vs. 5-fold and 6- vs. 4-fold, respectively). In liver, the abundance of IR, IRS-1, and IRS-2 was similar at 7 and 26 days of age. Feeding increased the activation of IR, IRS-1, IRS-2, and PI 3-kinase in liver only twofold, and these responses were unaffected by age. Thus our findings demonstrate that the feeding-induced activation of IR, IRS-1, IRS-2, and PI 3-kinase in skeletal muscle decreases with development. Further study is needed to ascertain whether the developmental decline in the feeding-induced activation of early insulin-signaling components contributes to the developmental decline in translation initiation in skeletal muscle.

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Aortic vasoreactivity during a postnatal critical window of the pancreas in rats

et al. 2010

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Changes in aortic vasoreactivity during the postnatal pancreatic critical window, where insulin and glucose, which modify vasoreactivity, are elevated, were studied and compared to those in control and metabolic syndrome (MS) rats. Twelve 21- and 28-day-old rats were used. To develop MS rats, male Wistar animals were given 30% sucrose in drinking water since weaning and used when 6 months old. Glucose and insulin levels were higher during suckling and decreased after weaning, and insulin and triglycerides levels increased in MS rats. Contraction elicited by norepinephrine (NE) was stronger than KCl contraction at all ages. KCl-induced contraction increased with, age being stronger in control rats; it further increased in MS rats. Norepinephrine-induced contraction increased from day 12 to day 28 but stabilized from day 21 to day 28; it was stronger in controls and increased in MS rats. Vasorelaxation to acetylcholine in NE precontracted rings did not change during the neonatal period, being similar to MS rats and lower than in controls. Insulin-induced increase in contraction elicited by KCl increased from day 12 to day 28 and increased from control to MS rats. There is a postnatal critical window in vasoreactivity that might predispose to cardiovascular diseases in adults.

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Insulin Receptor Number and Binding Affinity in Newborn Dogs

Cited by 9 publications

References 6 publications

Insulin binding characteristics in canine muscle tissue: effects of the estrous cycle phases

Insulin binding characteristics in canine muscle tissue: effects of the estrous cycle phases

Developmental changes in the feeding-induced activation of the insulin-signaling pathway in neonatal pigs

Aortic vasoreactivity during a postnatal critical window of the pancreas in rats

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