Artículos de revistas
Decreased β-cell Insulin Secretory Function In Aged Rats Due To Impaired Ca2+ Handling
Registro en:
Experimental Physiology. , v. 97, n. 9, p. 1065 - 1073, 2012.
9580670
10.1113/expphysiol.2012.064790
2-s2.0-84865533300
Autor
Ribeiro R.A.
Batista T.M.
Coelho F.M.
Boschero A.C.
Lopes G.S.
Carneiro E.M.
Institución
Resumen
Ageing is associated with an increased impairment in glucose homeostasis and an increased incidence of type 2 diabetes. In this study, we evaluated β-cell function and its implications for glucose homeostasis in 24-month-old female Wistar rats. Aged rats showed lower plasma glucose levels in the fed and fasting states compared with control rats. In addition, insulinaemia in the fed state was reduced in the older rats. Insulin receptor β (IRβ) expression was lower in the livers of the aged animals, whereas IRβ and Akt1/2/3 protein expressions were higher in the muscles. These effects may contribute to the normal glucose tolerance observed in older rodents. Isolated islets from aged rats secreted less insulin in response to 8.3 and 16.7 mm glucose. Accordingly, this group presented a lower [Ca2+]i in the presence of glucose and a depolarizing stimulus (30 mm K+). In addition, islets from aged rats showed reduced insulin secretion in response to 100 μm carbachol (CCh), 10 nm phorbol 12-myristate 13-acetate and 10 μm forskolin. The expressions of protein kinase C, protein kinase A and exocytotic proteins, such as syntaxin 1 and synaptosomal-associated protein 25 kDa (SNAP-25), were similar in islets from aged and control rats. In conclusion, our evidence suggests that the increased incidence of type 2 diabetes with age may be due to a progressive decline in β-cell secretory capacity due to disruption of Ca2+ handling. Furthermore, the expression of proteins of the insulin transduction cascade showed an adaptive profile, with a compensatory increase in IRβ and Akt1/2/3 in gastrocnemius muscles, which may maintain normal glucose homeostasis in 24-month-old rats. © 2012 The Physiological Society. 97 9 1065 1073 Ammon, H.P., Amm, U., Eujen, R., Hoppe, E., Trier, G., Verspohl, E.J., The role of old age in the effects of glucose on insulin secretion, pentosephosphate shunt activity, pyridine nucleotides and glutathione of rat pancreatic islets (1984) Life Sci, 34, pp. 247-257 Ammon, H.P., Fahmy, A., Mark, M., Wahl, M.A., Youssif, N., The effect of glucose on insulin release and ion movements in isolated pancreatic islets of rats in old age (1987) J Physiol, 384, pp. 347-354 Bradford, M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal Biochem, 72, pp. 248-254 Butler, A.E., Janson, J., Bonner-Weir, S., Ritzel, R., Rizza, R.A., Butler, P.C., β-Cell deficit and increased β-cell apoptosis in humans with type 2 diabetes (2003) Diabetes, 52, pp. 102-110 Chang, A.M., Halter, J.B., Aging and insulin secretion (2003) Am J Physiol Endocrinol Metab, 284, pp. E7-E12 Chiu, K.C., Lee, N.P., Cohan, P., Chuang, L.M., Beta cell function declines with age in glucose tolerant Caucasians (2000) Clin Endocrinol (Oxf), 53, pp. 569-575 Coon, P.J., Rogus, E.M., Drinkwater, D., Muller, D.C., Goldberg, A.P., Role of body fat distribution in the decline in insulin sensitivity and glucose tolerance with age (1992) J Clin Endocrinol Metab, 75, pp. 1125-1132 Cowie, C.C., Rust, K.F., Byrd-Holt, D.D., Eberhardt, M.S., Flegal, K.M., Engelgau, M.M., Saydah, S.H., Gregg, E.W., Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population: National Health And Nutrition Examination Survey 1999-2002 (2006) Diabetes Care, 29, pp. 1263-1268 Cowie, C.C., Rust, K.F., Ford, E.S., Eberhardt, M.S., Byrd-Holt, D.D., Li, C., Williams, D.E., Geiss, L.S., Full accounting of diabetes and pre-diabetes in the U.S. population in 1988-1994 and 2005-2006 (2009) Diabetes Care, 32, pp. 287-294 Delmeire, D., Flamez, D., Hinke, S.A., Cali, J.J., Pipeleers, D., Schuit, F., Type VIII adenylyl cyclase in rat beta cells: coincidence signal detector/generator for glucose and GLP-1 (2003) Diabetologia, 46, pp. 1383-1393 Dyachok, O., Idevall-Hagren, O., Sågetorp, J., Tian, G., Wuttke, A., Arrieumerlou, C., Akusjärvi, G., Tengholm, A., Glucose-induced cyclic AMP oscillations regulate pulsatile insulin secretion (2008) Cell Metab, 8, pp. 26-37 Eliasson, L., Abdulkader, F., Braun, M., Galvanovskis, J., Hoppa, M.B., Rorsman, P., Novel aspects of the molecular mechanisms controlling insulin secretion (2008) J Physiol, 586, pp. 3313-3324 Gómez-Pérez, Y., Gianotti, M., Proenza, A.M., Lladó, I., Age-related decline of skeletal muscle insulin sensitivity in rats: effect of sex and muscle type (2011) Rejuvenation Res, 14, pp. 153-161 Gunasekaran, U., Gannon, M., Type 2 diabetes and the aging pancreatic beta cell (2011) Aging (Albany NY), 3, pp. 565-575 Ihm, S.H., Moon, H.J., Kang, J.G., Park, C.Y., Oh, K.W., Jeong, I.K., Oh, Y.S., Park, S.W., Effect of aging on insulin secretory function and expression of beta cell function-related genes of islets (2007) Diabetes Res Clin Pract, 77 (SUPPL 1), pp. S150-S154 Iwashima, Y., Abiko, A., Ushikubi, F., Hata, A., Kaku, K., Sano, H., Eto, M., Downregulation of the voltage-dependent calcium channel (VDCC) β-subunit mRNAs in pancreatic islets of type 2 diabetic rats (2001) Biochem Biophys Res Commun, 280, pp. 923-932 Kahn, S.E., Hull, R.L., Utzschneider, K.M., Mechanisms linking obesity to insulin resistance and type 2 diabetes (2006) Nature, 444, pp. 840-846 Kato, S., Ishida, H., Tsuura, Y., Tsuji, K., Nishimura, M., Horie, M., Taminato, T., Seino, Y., Alterations in basal and glucose-stimulated voltage-dependent Ca2+ channel activities in pancreatic beta cells of non-insulin-dependent diabetes mellitus GK rats (1996) J Clin Invest, 97, pp. 2417-2425 Maedler, K., Schumann, D.M., Schulthess, F., Oberholzer, J., Bosco, D., Berney, T., Donath, M.Y., Aging correlates with decreased β-cell proliferative capacity and enhanced sensitivity to apoptosis: a potential role for Fas and pancreatic duodenal homeobox-1 (2006) Diabetes, 55, pp. 2455-2462 Muzumdar, R., Ma, X., Atzmon, G., Vuguin, P., Yang, X., Barzilai, N., Decrease in glucose-stimulated insulin secretion with aging is independent of insulin action (2004) Diabetes, 53, pp. 441-446 Nagamatsu, S., Nakamichi, Y., Yamamura, C., Matsushima, S., Watanabe, T., Ozawa, S., Furukawa, H., Ishida, H., Decreased expression of t-SNARE, syntaxin 1, and SNAP-25 in pancreatic β-cells is involved in impaired insulin secretion from diabetic GK rat islets: restoration of decreased t-SNARE proteins improves impaired insulin secretion (1999) Diabetes, 48, pp. 2367-2373 Reers, C., Erbel, S., Esposito, I., Schmied, B., Buchler, M.W., Nawroth, P.P., Ritzel, R.A., Impaired islet turnover in human donor pancreata with aging (2009) Eur J Endocrinol, 160, pp. 185-191 Ribeiro, R.A., Vanzela, E.C., Oliveira, C.A., Bonfleur, M.L., Boschero, A.C., Carneiro, E.M., Taurine supplementation: involvement of cholinergic/phospholipase C and protein kinase A pathways in potentiation of insulin secretion and Ca2+ handling in mouse pancreatic islets (2010) Br J Nutr, 104, pp. 1148-1155 Roe, M.W., Worley 3rd, J.F., Tokuyama, Y., Philipson, L.H., Sturis, J., Tang, J., Dukes, I.D., Polonsky, K.S., NIDDM is associated with loss of pancreatic beta-cell L-type Ca2+ channel activity (1996) Am J Physiol Endocrinol Metab, 270, pp. E133-E140 Scheen, A.J., Diabetes mellitus in the elderly: insulin resistance and/or impaired insulin secretion? (2005) Diabetes Metab, 31 (SPEC NO 2), pp. 5S27-5S34 Schulla, V., Renström, E., Feil, R., Feil, S., Franklin, I., Gjinovci, A., Jing, X.J., Hofmann, F., Impaired insulin secretion and glucose tolerance in β cell-selective Cav1.2 Ca2+ channel null mice (2003) EMBO J, 22, pp. 3844-3854 Tengholm, A., Gylfe, E., Oscillatory control of insulin secretion (2009) Mol Cell Endocrinol, 297, pp. 58-72 Thore, S., Dyachok, O., Gylfe, E., Tengholm, A., Feedback activation of phospholipase C via intracellular mobilization and store-operated influx of Ca2+ in insulin-secreting β-cells (2005) J Cell Sci, 118, pp. 4463-4471 Thore, S., Wuttke, A., Tengholm, A., Rapid turnover of phosphatidylinositol-4,5-bisphosphate in insulin-secreting cells mediated by Ca2+ and the ATP-to-ADP ratio (2007) Diabetes, 56, pp. 818-826 Tschen, S.I., Dhawan, S., Gurlo, T., Bhushan, A., Age-dependent decline in β-cell proliferation restricts the capacity of β-cell regeneration in mice (2009) Diabetes, 58, pp. 1312-1320 Vikman, J., Ma, X., Hockerman, G.H., Rorsman, P., Eliasson, L., Antibody inhibition of synaptosomal protein of 25 kDa (SNAP-25) and syntaxin 1 reduces rapid exocytosis in insulin-secreting cells (2006) J Mol Endocrinol, 36, pp. 503-515 Yang, S.N., Berggren, P.O., The role of voltage-gated calcium channels in pancreatic β-cell physiology and pathophysiology (2006) Endocr Rev, 27, pp. 621-676