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4. Glucagon-like peptide-1 accelerates the onset of insulin action on glucose disappearance in mice

Author

Thomaseth, K., Pavan, A., Pacini, G., and Ahren, B.

Subjects
Glucose metabolism -- Research, Homeostasis -- Research, Insulin -- Research, Mathematical models -- Usage, Peptides -- Research, Biological sciences
Abstract

Glucagon-like peptide-1 (GLP-1) plays a significant role in glucose homeostasis through its incretin effect on insulin secretion. However, GLP-1 also exhibits extrapancreatic actions, and in particular its possible influences on insulin sensitivity are controversial. To study the dynamic action of GLP-1 on insulin sensitivity, we applied advanced statistical modeling methods to study glucose disappearance in mice that underwent intravenous glucose tolerance test with administration of GLP-1 at various dose levels. In particular, the minimal model of glucose disappearance was exploited within a population estimation framework for accurate detection of relationships between glucose disappearance parameters and GLP-1. Minimal model parameters were estimated from glucose and insulin data collected in 209 anesthetized normal mice after intravenous injection of glucose (1 g/kg) alone or with GLP-1 (0.03-100 nmol/kg). Insulin secretion markedly increased, as expected, with increasing GLP-1 dose. However, minimal model-derived indexes, i.e., insulin sensitivity and glucose effectiveness, did not significantly change with GLP-1 dose. Instead, fractional turnover rate of insulin action [[P.sub.2] = 0.0207 [+ or -] 24.3% (min) at zero GLP-1 dose] increased steadily with administered GLP-1 dose, with significant differences at 10.4 nmol/kg ([P.sub.2] = 0.040 [+ or -] 15.5%, P = 0.0046) and 31.2 nmol/kg ([P.sub.2] = 0.050 [+ or -] 29.2%, P = 0.01). These results show that GLP-1 influences the dynamics of insulin action by accelerating insulin action following glucose challenge. This is a novel mechanism contributing to the glucose-lowering action of GLP-1. glucose kinetics; insulin secretion; insulin sensitivity; mathematical modeling; minimal model doi:10.1152/ajpendo.00303.2006.

Published
2007

5. Insulin sensitivity, fat distribution, and adipocytokine response to different diets in lean and obese cats before and after weight loss

Author

Hoenig, M., Thomaseth, K., Waldron, M., and Ferguson, D.C.

Subjects
Obesity -- Health aspects, Obesity -- Research, Weight loss -- Health aspects, Weight loss -- Research, Reducing diets -- Health aspects, Reducing diets -- Research, Biological sciences
Abstract

Obesity is a major health problem in cats and a risk factor for diabetes. It has been postulated that cats are always gluconeogenic and that the rise in obesity might be related to high dietary carbohydrates. We examined the effect of a high-carbohydrate/ low-protein (HC) and a high-protein/low-carbohydrate (HP) diet on glucose and fat metabolism during euglycemic hyperinsulinemic clamp, adipocytokines, and fat distribution in 12 lean and 16 obese cats before and after weight loss. Feeding diet HP led to greater heat production in lean but not in obese cats. Regardless of diet, obese cats had markedly decreased glucose effectiveness and insulin resistance, but greater suppression of nonesterified fatty acids during the euglycemic hyperinsulinemic clamp was seen in obese cats on diet HC compared with lean cats on either diet or obese cats on diet HP. In contrast to humans, obese cats had abdominal fat equally distributed subcutaneously and intra-abdominally. Weight loss normalized insulin sensitivity; however, increased nonesterified fatty acid suppression was maintained and fat loss was less in cats on diet HC. Adiponectin was negatively and leptin positively correlated with fat mass. Lean cats and cats during weight loss, but not obese cats, adapted to the varying dietary carbohydrate/protein content with changes in substrate oxidation. We conclude that diet HP is beneficial through maintenance of normal insulin sensitivity of fat metabolism in obese cats, facilitating the loss of fat during weight loss, and increasing heat production in lean cats. These data also show that insulin sensitivity of glucose and fat metabolism can be differentially regulated in cats. euglycemic hyperinsulinemic clamp; indirect calorimetry; obesity; diabetes; leptin; adiponectin; magnetic resonance imaging

Published
2007

9. Distribution and kinetics of amylin in humans

Author

Clodi, M., Thomaseth, K., Hermann, K., Kautzky-Willer, A., Waldhausl, W., Prager, R., and Ludvik, B.

Subjects
Amylinamide -- Research, Peptides -- Research, Biological sciences
Abstract

Research was conducted to determine the apparent volume of distribution (V(sub TOT)), fractional clearance, total body clearance (CL) and mean residence time (MRT) of the beta-cell hormone amylin. Nine healthy male subjects were injected with 50 micrograms of human synthetic amilin and plasma levels of amylin concentrations were examined using three-exponential curves. Results indicate that clearance of amylin is the same as that of C-peptide and relatively slower than insulin.

Published
1998

17. Parameter Estimation of a Model for Baroreflex Control of Unstressed Volume

Author

Thomaseth K., Batzel J., Bachar M., and Furlan R.

Abstract

The baroreflex involves a number of control pathways. In this Chapter we consider in greater detail the role of the control of unstressed volume mobilization. We also consider an alternative approach for choosing parameters most likely to be estimable and we apply this method to a model incorporating the control of unstressed volume and compare to data.

Published
2013

18. Cats differ from other species in their cytokine and antioxidant enzyme response when developing obesity

Author

Hoenig M., Pach N., Thomaseth K., Le A., Schaeffer D., and Ferguson D.C.

Subjects
lipid storage, insulin, proinsulin, obesity, animal experiment, interleukin 6, animal cell, interleukin 1, leptin, animal tissue, male, insulin sensitivity, oxidative stress, controlled study, glutathione peroxidase, tumor necrosis factor alpha, nonhuman, adiponectin, concentration (parameters), catalase, species difference, article, experimental cat, longitudinal study, glucose transport, fat mass, weight gain, thermogenesis, sex ratio, superoxide dismutase, enzyme activity, female, inflammation, intravenous glucose tolerance test
Abstract

Objectives: Obese cats show many similarities to obese people, including insulin resistance and an increased diabetes risk. However, atherosclerosis and cardiovascular disease are not seen in cats. In people, they are associated with the development of an inflammatory response, which, we hypothesized, does not occur in cats. Design and Methods: Twenty neutered cats of equal gender distribution were allowed to gain weight by offering food ad libitum and were examined before and at 10, 30, 60, and 100% weight gain. All cats reached 60% of weight gain, 12 cats gained 100 % in 12 months. Results: Fat was equally distributed between subcutaneous and visceral depots. Insulin-independent glucose uptake increased and insulin sensitivity decreased with increasing adiposity. However, baseline glucose concentrations were unchanged suggesting a decrease in EGP. Inflammatory cytokines (Il-1, IL-6, TNFa) and catalase, superoxide dismutase, glutathione peroxidase did not change. Insulin, proinsulin, and leptin were positively and adiponectin negatively correlated with adiposity. Heat production increased with obesity, but became less when body weight gain was > 60 %. Conclusions: This indicates that metabolism adapts more appropriately to the higher intake of calories in the initial phase of obesity but slows at higher body fat content. This likely contributes to the difficulty to lose weight. Copyright

Published
2013
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45. Progression & risk factors CKD 1-5 (2)

Author

Bouba, I., primary, Bountouri, C., additional, Dounousi, E., additional, Kiatou, V., additional, Georgiou, I., additional, Chatzidakis, S., additional, Kotzadamis, N., additional, Tsakiris, D., additional, Siamopoulos, K., additional, Dimas, G., additional, Iliadis, F., additional, Tegos, T., additional, Makedou, K., additional, Didangelos, T., additional, Pitsalidis, C., additional, Chatziapostolou, A., additional, Makedou, A., additional, Baloyannis, S., additional, Grekas, D., additional, Li, O., additional, Bobkova, I., additional, Tchebotareva, N., additional, Kozlovskaya, L., additional, Varshavskiy, V., additional, Mydlik, M., additional, Derzsiova, K., additional, Bohu , B., additional, Clapp, E., additional, Kosmadakis, G., additional, Smith, A., additional, Viana, J., additional, Shirreffs, S., additional, Maughan, R., additional, Feehally, J., additional, Bevington, A., additional, Ando, M., additional, Yanagisawa, N., additional, Hara, M., additional, Tsuchiya, K., additional, Nitta, K., additional, Chen, C.-H., additional, Wang, C.-L., additional, Huang, J.-W., additional, Hung, K.-Y., additional, Tsai, T.-J., additional, Gadalean, F., additional, Gluhovschi, G., additional, Kaycsa, A., additional, Trandafirescu, V., additional, Petrica, L., additional, Velciov, S., additional, Bozdog, G., additional, Gluhovschi, C., additional, Bob, F., additional, Solberg Eikrem, O., additional, Hope Jaeger-Hoie, E., additional, Hausken, T., additional, Svarstad, E., additional, de Goeij, M., additional, Liem, M., additional, de Jager, D., additional, Voormolen, N., additional, Sijpkens, Y., additional, Boeschoten, E., additional, Dekker, F., additional, Grootendorst, D., additional, Halbesma, N., additional, Moran, A.-M., additional, Kenny, E., additional, Ward, F., additional, Dunne, O. M., additional, Holian, J., additional, Watson, A. J., additional, Saginova, E., additional, Gallyamov, M., additional, Severova, M., additional, Surkova, O., additional, Fomin, V., additional, Topchii, I., additional, Kirienko, A., additional, Schenyavskaya, E., additional, Efimova, N., additional, Bondar, T., additional, Lesovaja, A., additional, Gama Axelsson, T., additional, Barany, P., additional, Heimburger, O., additional, Lindholm, B., additional, Stenvinkel, P., additional, Qureshi, A. R., additional, Bal, Z., additional, Erkmen Uyar, M., additional, Ahmed, N., additional, Tutal, E., additional, Sezer, S., additional, Labrador, P. J., additional, Gonzalez Castillo, P. M., additional, Silva Junior, G. B., additional, Liborio, A. B., additional, Lopes Filho, A. S., additional, Figueiredo Filho, A. C., additional, Vieira, A. P. F., additional, Couto Bem, A. X., additional, Guedes, A. L. M. O., additional, Costa, C. M. B. E., additional, Holanda de Souza, J., additional, Daher, E. F., additional, Donadio, C., additional, Kanaki, A., additional, Tognotti, D., additional, Donadio, E., additional, Reznik, E., additional, Guschina, V., additional, Volinkina, V., additional, Gendlin, G., additional, Storozhakov, G., additional, Capusa, C., additional, Stancu, S., additional, Badulescu, M., additional, Ilyes, A., additional, Anghel, C., additional, Mircescu, G., additional, Yonemoto, S., additional, Fujii, N., additional, Hamano, T., additional, Okuno, A., additional, Soda, T., additional, Yamanaka, K., additional, Hirai, T., additional, Nishimura, K., additional, Ichikawa, Y., additional, Boudville, N., additional, Kemp, A., additional, Champion de Crespigny, P., additional, Fassett, R., additional, Healy, H., additional, Mangos, G., additional, Moody, H., additional, Pedagogos, E., additional, Waugh, D., additional, Kirkland, G., additional, Kay, T., additional, Hoffman, D., additional, Abaterusso, C., additional, Branco, C., additional, Thomaseth, K., additional, Graziani, M. S., additional, Lupo, A., additional, Chaudhry, M., additional, Lok, C., additional, Kudo, K., additional, Konta, T., additional, Takasaki, S., additional, Degawa, N., additional, Kubota, I., additional, Nykula, T., additional, Moyseyenko, V., additional, Topchii, A., additional, Nanami, K., additional, Yoshiharu, T., additional, Hiroshi, Y., additional, Miyuki, M., additional, Masayuki, N., additional, Sotila, G. G., additional, Rugina, S., additional, Tuta, L., additional, Dumitru, I., additional, Cernat, R., additional, Rugina, C., additional, Kim, I. Y., additional, Lee, S. B., additional, Choi, B. K., additional, Son, J., additional, Lee, H. S., additional, Lee, N., additional, Rhee, H., additional, Song, S. H., additional, Seong, E. Y., additional, and Kwak, I. S., additional

Published
2011
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