Characterization and Comparison of Insulin Resistance Induced by Cushing Syndrome or Diestrus against Healthy Control Dogs as Determined by Euglycemic- Hyperinsulinemic Glucose Clamp Profile Glucose Infusion Rate Using an Artificial Pancreas Apparatus

Fukuta, Hiroko; Mori, Akira; Urumuhan, Nazarbek; Lee, Peter; Oda, Hitomi; Saeki, Kiyomi; Kurishima, Miyuki; Nozawa, Satoshi; Mizutani, H.; Mishina, Suguru; Arai, Toshiro; Sako, Toshinori

doi:10.1292/jvms.12-0041

Cited by 8 publications

(7 citation statements)

References 23 publications

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“…We previously studied different insulin sensitivity indexes in the cohort from which the bitches of this study were selected, and despite higher values for different insulin sensitivity indexes during estrus and diestrus, no significant statistical difference was found (Pöppl et al, 2009). Nevertheless, Fukuta et al (2012), using the euglycemic--hyperinsulinemic glucose clamp, demonstrated a 40% reduction in insulin sensitivity in bitches in diestrus despite no differences in baseline insulin or baseline glucose plasma concentrations. Moreover, Mared et al (2012) in a longitudinal study of Elkhounds during anestrus and diestrus documented higher C-peptide plasma concentration and HOMA-B, and a lower HOMA-S during diestrus (and higher progesterone concentration), despite no difference in GH or IGF-I levels.…”

Section: Discussionmentioning

confidence: 90%

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: Discussionmentioning

confidence: 90%

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

et al. 2016

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“…Alef et al (2008) não encontrou relações significativas entre a idade e a ureia. Entretanto, Fukuda et al (2012) também verificou aumento da ureia com envelhecimento. Da mesma maneira Comazzi et al (2004) encontraram valores significativamente maiores em animais geriátricos do que em animais de meia-idade.…”

Section: Resultsunclassified

Assessment of alterations in biochemical exams indicative of renal and hepatic function concerning sex and in elderly and geriatric dogs - a retrospective study between 2015 and 2017 in Joinville - SC

Finsterbuch

Martins

Medeiros³

et al. 2018

Pubvet

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“…In the current study, we have not analyzed GLUT-4 variations. The GIR of HAC dogs had been significantly lower than those of control dogs in our previous study [15], suggesting that GLUT-4 located in cell membranes had decreased in HAC dogs, although it is unclear if it decreased at a transcriptional level. A further study is necessary to clarify the transcriptional modulation of GLUT-4 in HAC dogs.…”

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confidence: 78%

“…The initial report suggesting that aPKC is required for insulin-stimulated glucose transport describes that inactive (dominant-negative) forms of these protein kinases cause inhibitory effects on insulin action in adipocytes and muscular cells [3, 19, 38, 44]. In our previous report, we measured glucose infusion rates (GIR) of HAC dogs by euglycemic-hyperinsulinemic glucose clamp (EHGC) method using an artificial pancreas apparatus [15]. EHGC method [12] is a gold standard for assessing insulin resistance in human skeletal muscles [18].…”

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confidence: 99%

“…EHGC method [12] is a gold standard for assessing insulin resistance in human skeletal muscles [18]. When GIR in the HAC dogs were compared with those in normal dogs, the HAC dogs showed lower GIR than normal ones, indicating that the HAC dogs are suffering from insulin resistance as well as human patients [15]. The mechanism of insulin resistance may include transcriptional, translational and activational modulations of insulin signal molecules.…”

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confidence: 99%

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Decreased Gene Expressions of Insulin Signal Molecules in Canine Hyperadrenocorticism

Nozawa

Oda

Akiyama

et al. 2014

The Journal of Veterinary Medical Science

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Hyperadrenocorticism (HAC) is a common endocrine disorder in dogs, in which excess glucocorticoid causes insulin resistance. Disturbance of insulin action may be caused by multiple factors, including transcriptional modulation of insulin signal molecules which lie downstream of insulin binding to insulin receptors. In this study, gene expressions of insulin signal molecules were examined using neutrophils of the HAC dogs (the untreated dogs and the dogs which had been treated with trilostane). Insulin receptor substrate (IRS)-1, IRS-2, phosphatidylinositol 3-kinase (PI3-K), protein kinase B/Akt kinase (Akt)-2 and protein kinase C (PKC)-lambda were analyzed in the HAC dogs and compared with those from normal dogs. The IRS-1 gene expressions decreased by 37% and 35% of the control dogs in the untreated and treated groups, respectively. The IRS-2 gene expressions decreased by 61% and 72%, the PI3-K gene expressions decreased by 47% and 55%, and the Akt-2 gene expressions decreased by 45% and 56% of the control dogs, similarly. Collectively, gene expressions of insulin signal molecules are suppressed in the HAC dogs, which may partially contribute to the induction of insulin resistance.

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Characterization and Comparison of Insulin Resistance Induced by Cushing Syndrome or Diestrus against Healthy Control Dogs as Determined by Euglycemic- Hyperinsulinemic Glucose Clamp Profile Glucose Infusion Rate Using an Artificial Pancreas Apparatus

Cited by 8 publications

References 23 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

Assessment of alterations in biochemical exams indicative of renal and hepatic function concerning sex and in elderly and geriatric dogs - a retrospective study between 2015 and 2017 in Joinville - SC

Decreased Gene Expressions of Insulin Signal Molecules in Canine Hyperadrenocorticism

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